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00:00:00
thank you for that uh a very strong introduction um ah yeah i am
00:00:07
flattered to be you know the program and pleased to be here
00:00:10
and uh the the context of my of my top on user is
00:00:16
obesity and it's in its provenance so shown here uh is
00:00:22
oh that there is a clear association
00:00:26
between the disease prevalence is all of a number of significant diseases
00:00:31
that we need humans it into the health care system
00:00:34
uh and uh that are that are associated attributable to
00:00:38
would be sitting on this one of these associations are really quite strong because all of broader array of
00:00:45
evidence that supports this association in as a function of uh of data like these and others
00:00:52
uh and number of a national and international bodies have
00:00:56
deemed to to a scribe obesity as a disease
00:01:01
and given that disease status it's incumbent upon the medical community
00:01:05
to come up with attractive to it's so the
00:01:09
the organisation of my talk is as follows on going to work support the idea
00:01:14
would tend to support the idea that hi fader is driving obesity problems
00:01:19
ah and then i'm going to transition to to the nervous system in various ways first to focus attention
00:01:26
on the role of neural circuits that are
00:01:29
involved in uh in facilitating eating
00:01:33
as a function of choose from the uh it from the fruit environment
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uh next i will consider a different sort of circuits
00:01:42
they're involved in the normal control of intake inhibition
00:01:45
particularly when you take in addition to its associated with consuming food
00:01:51
and from there i will uh consider very for for one of the approved yet you b. c. d. drugs
00:01:58
oh the the neural plan aspect of it a neural control and assert
00:02:03
that oh the action of the use of this particular drop type
00:02:07
uh has its effect by working well coincidentally with uh
00:02:11
the same circuits that media can tardiness control wheels
00:02:15
and finally i will make the point that uh not only does the do
00:02:19
we have to be easy to drugs particularly the g. o. p. drugs
00:02:22
well reduce intake but they re does it take as a
00:02:25
function of interfering with or reducing the attractiveness of
00:02:31
they had on the quality of fruit reduced would seeking in the reduce motivation to get some food
00:02:37
so for some support for the idea that a high percentage is a major driver of obesity
00:02:44
oh there are broader into data for broader a ray of data that would support this but here's two types
00:02:51
the the user data from popular daffy they uh they uh they track as
00:02:56
a function of p. of time period going from earlier to later
00:03:00
uh on uh the number of feeding opportunities or own meals
00:03:05
and snacks today in us children and us adults
00:03:09
and if we look at the colour coding what we conclude is what the authors conclude is
00:03:13
that as a function of time well uh humans uh us us uh children and adults
00:03:20
or increasing the number of heating up achieved today me a watch
00:03:25
the next obvious question is a while they're increasing in frequency is the only any support for the idea that
00:03:31
the increase in the size of meals because some of those two things that determine total daily caloric intake
00:03:37
and so what we've heard about the the contribution of portion sizes stated portion
00:03:42
size object for user some uh some data from uh livingston slap
00:03:47
uh they evaluated in adult human development um and and and
00:03:51
and women over sixty feeding opportunities for per day
00:03:56
the effect of serving these individuals a regular sized portion or an enlarged pores
00:04:02
and as a function of simply being confronted with you lord portion men
00:04:07
consume seventy percent greater energy and women consumed ten percent greater energy
00:04:14
uh this is not a rare finding there are many other studies
00:04:18
that support it one here from the barber roles group
00:04:21
well i analysts in these effects over eleven the puget sound support support that was all
00:04:28
now i wanna make a transition from oh what i just described as evidence supporting the
00:04:33
idea that we're eating more calories and that's why we're uh we're gaining more weight
00:04:38
oh and make a transition into is considering the role of the
00:04:41
nervous system because clearly the water systems the organ of behaviour
00:04:45
and so i'll uh what i'm describing here is a set of data that has been replicated many towns
00:04:52
so all the conclusions from this uh i think or or well established and this is an f. summarise study
00:04:59
uh which is basically measuring blood flow as a proxy of measuring change a new elected
00:05:06
um and what we're measuring here these studies is uh
00:05:10
the humans are the atom wrong they have access
00:05:14
to a visual images the images could be of a high energy that's foods such as these
00:05:20
low energy dense foods imagine caleb broccoli and pictures of us scenes having nothing to do with you
00:05:26
and if we compare the change and blood flow to various places in the brain
00:05:31
the uh between the energy dense food and and it and and and and uh and
00:05:36
the low energy that's fruit effect of the energy tends to this to increase
00:05:41
neural activity in a number of key size within the brain what all the stuff that's
00:05:45
they could be uh oh out to sell roots in the in the mid brain that make doubly
00:05:52
since the original identity and and those those uh those double mean urged neurons are known
00:05:58
to project directly to destroy them all to dorsal and ventral portion of the sprite
00:06:03
it it so that those regions are activated the insular cortex is activated the
00:06:08
it's we're cortex process is a variety of of sensory signals including customers
00:06:14
their regions wouldn't doubt mister activated and i put on the so collectively
00:06:18
what this suggests with that simply viewing an image of energy density
00:06:24
drives narrow lack direct drive neural activity in regions of the brain that are associated with this creation of the
00:06:29
open it and we know that don't mean a bit
00:06:32
open mean a accent circuits to facilitate repetitive behaviour
00:06:37
let's support for the idea that that this type of data is consistent with the
00:06:42
idea that opening is released by tasting food is found in the next study
00:06:48
this is a pet starting you otherwise is a c. forty racked upright rapid pride
00:06:54
is a an antagonist of the dope an interceptor so the logic of this experiment is
00:06:59
if uh if if the c. forty is being bound to to drop them interceptors
00:07:06
then if dopey mean was released and dodges sleek and the
00:07:10
releases doberman should displace their thing that bound c. forty
00:07:15
and so in this study by small and and colleagues see uh see for each
00:07:21
of the so that each of the subjects determine what their favourite from what's
00:07:25
in in the context of the study the individuals not to sample their favourite too
00:07:30
and as a function of simply sampling i favoured fruit what they determined is
00:07:36
but there is a significant reduction in rapid pride by the net is directly
00:07:40
supports the idea that simply tasting this from drives dope and squishy
00:07:47
well that was human data using one kind of technology
00:07:51
the user animal data using more sophisticated technology
00:07:56
we can measure don't meet accretion in real time using collectible t. ball ten actually
00:08:02
and these are data coming from which weapons lab is a collaborator and and former student of mine
00:08:08
it is it is it hot bartender treated measured openly secretion in with electrodes
00:08:13
uh uh uh electrode a terminating in the ventral strident
00:08:18
what i observed here is that simply infusing sucrose into the oral cavity
00:08:24
um i i it immediately elevates nobody's creation within this right
00:08:29
by contrast quite nine which elicits a completely different response in is rejected
00:08:34
can drive through or adoption in dope and it's a grudge
00:08:38
i mean as a comparison between two are to scan really the humans would describe the sweet
00:08:44
um and what we observe here is that the nutrients sucrose and the not
00:08:50
guilty it's accurate both drive increases and told me in real time
00:08:57
no one about to show you one of blank screen represents a an idea and the idea is that
00:09:04
i just described in showed you both in humans and
00:09:06
animals that are tasting a favourite food energy
00:09:10
tends to or tasting should or or saccharin will will drive up the secretion of the open
00:09:17
uh i will show though so it's so this to me
00:09:19
we are the what what psychologist would call primary reinforce
00:09:24
but primarily it forces or are a subject could be
00:09:27
associated with other events that pretty big though
00:09:31
so if you had an animal that was pressing a ball to obtain issue the pellet
00:09:35
and you get and you made that contingency could consistent then the bar itself would come to to creep up
00:09:42
if you put yeah one special environment and the environment had aligned to the animal began
00:09:47
to associate ally with access to the bark that protected the delivery of sugar
00:09:53
then simply viewing the light come on we drive the secretion
00:09:57
and so that's what you're gonna observe in those little video yeah animal big isn't
00:10:02
the end of one trial in moves to the right and you and
00:10:06
so you did any of the animals on top and the dog would mean
00:10:09
the dummy secretion in the commons in real time as shown below
00:10:20
but like comes on top in the opening levels right now the
00:10:24
animal presses the bar now the animal consumes you should
00:10:28
but for the association between the place the lever on the shoulder should overall
00:10:34
was riding don't it now the animal has learned to associate projectors
00:10:40
of access to win consumption of energy dense food with reward reward
00:10:46
protection and so i would assert we are when we talk
00:10:50
about changes in the phone environment we're not just talking about availability
00:10:54
of energy dense food we're talking about the power of
00:10:58
of our brains to make associations and it's it's eating folded
00:11:02
up eating energy that's put into place didn't even before
00:11:06
you are in you or a prime to return to that place what if we get
00:11:14
making a transition now to the next topic and that is uh
00:11:18
the the the neural system that mediates a new termination
00:11:22
i know i wanna assert that you need not go further than the
00:11:26
g. i. tract and signals that or gauged by the consumption
00:11:31
just long live the neural control you'll size neural control they can push
00:11:36
so what we see here is a list of signals are battery
00:11:41
gauge the function of fruit flowing through the g. i. tract
00:11:44
we know they're coming out of the standing is only a chemical distinction or no other signals that are generated
00:11:49
but that's the food is that is a is a pass from this
00:11:53
topic to the small intestine arrays of other signals or leakage
00:11:58
oh each of these signals is capable of driving vehicle africa activity
00:12:04
and there's even evidence in the published literature that that the six
00:12:08
session of these activities synergy eyes is within the vase
00:12:14
so these are the signals and these are to be these data here provide support for the potency of g.
00:12:20
i. signals on intake behaviour to the user data come from a team or an important cues lab
00:12:26
they are involve non human primates the non human primates
00:12:30
and inserted with any dwelling gastric annular through which
00:12:34
the experimenter can infuse week we volume but differential quarry confusion
00:12:40
they range from zero calories to three hundred with two with immediate step
00:12:45
and the read out of the n. pact of the infused calorie differential calories
00:12:50
is the reduction in c. plus schedule me all that follows the infusion
00:12:55
what you can see here very portly with respect to the shape of this function is the
00:13:00
rainy yeah already of the intake inhibition are rising from calories delivered to the g. h.
00:13:07
oh
00:13:09
i wanna move more into more detailed fashion into the nervous system to consider the flow
00:13:15
of this information in the processing of this information and the idea that ah
00:13:20
that sells within the within that not all of which i will describe
00:13:24
or not only sites of receipt of this very collaborative permission
00:13:29
but also process all other intake inhibitory signals and amplify this this is that so
00:13:35
we begin with uh the intestines these are these boxes or nutrient this is an end to
00:13:41
end you can sell which is stimulated by the nutrients let's say that this is
00:13:44
a g. o. p. you are probably going celtic reading g. l. p.
00:13:48
one your p. one acts in the powerpoint fashion and activates the
00:13:52
distal a branch of this vocal effort use of the cell bodies of
00:13:56
of uh the big uh laugh rents a note of ganglia
00:13:59
express a variety of very interesting jeans and people are those are are describing now
00:14:04
the central terminal uh oh of these neurons are uh
00:14:08
make a cinematic contact in the portal medial
00:14:11
are a nucleus of the solitary track but further we know something about the cell type
00:14:17
but these very go after terminals on us interrupts apart now highlight two two types
00:14:24
while it's called me to work at a cold mean ron's these are neurons
00:14:28
that express tires eli jocks late or don't need a hard rocks ways
00:14:32
and the other or p. p. g. are pretty probably done around themselves
00:14:38
so here we have preprogrammed around in the intestine and now we
00:14:42
have three probably don neurons in the brain and it interact
00:14:46
impact the secretion in the intestine and the activation of the very guess
00:14:51
oh and the activation of these these next stage no it's
00:14:57
here they are here they are the green ones or the debris bit hard rock listener on
00:15:02
the red ones or the p. p. g. or the g. o. p. one runs
00:15:06
and from sly selector physiology using stimulation of the
00:15:10
of the solitary track which is a proxy for bigger reference stimulation
00:15:15
what these authors were able to determine is that is that big a laugh or an input
00:15:20
that impacts upon these probably done ron's stimulates directed
00:15:25
the same is the case for the tires the now drops lays neurons user data
00:15:31
are using c. boss as a marker of increased neural activity that demonstrates increased
00:15:36
uh increase activation of businesses or range of what it is with the idea
00:15:41
now for the times in iraq's lays neurons the very act sounds of them project to a
00:15:47
number of sites enough in before brain and then the ponds in in the mid break
00:15:52
and for me uh the p. p. g. inner ons that are
00:15:56
now providing the central and dodging the source of geo wow
00:16:00
the x. amount of these neurons to project again uh to raise of sites
00:16:06
maybe a dozen sites that express the g. l. p. one reset
00:16:10
so wonder in digest conditions when when ah a variety of of
00:16:15
digested nutrients are impacting upon this portion of the nervous system
00:16:20
there it's engaging on only their activity but it's activating the east these
00:16:24
two systems including the enlarging list g. o. p. c. still
00:16:28
to to activate the release a of g. l. p. at their axon
00:16:32
terminals and and and to facilitate joking movies multiple sites with right
00:16:40
now the next one i wanna make us is so let me describe doesn't look or two
00:16:45
record to show that we are thinner arms about far i describe the g. i. tract of these
00:16:50
very reference here to sell part and then out of nowhere exact the exact on terminals
00:16:56
or excite assault population around within the un t. i.'s we've just described that
00:17:01
i wanna go want to make the point that that that these very same nah
00:17:06
or not only driven by this intake inhibitory stimulating arising from ingestion
00:17:11
full but they also express receptors for number of interesting
00:17:15
things including lap and and oxen told and i'm gonna describe
00:17:19
the impact of a bad processing on the cells
00:17:24
uh_huh skip this one
00:17:27
so here we are uh that's the anatomy of this part of the brain is the area post remote this
00:17:32
is the fourth vegetables is the root problem a dollar this is the media o. n. t. s.
00:17:37
and i knew that who we just described at the cells are driven by they laugh instantly
00:17:44
it was no all that that in this region there were neurons that express the let the receptor
00:17:49
and we asked the question are they the same cell or cells that are very greed driven also express very
00:17:54
go uh also express not receptor so in collaboration we didn't experiment using in your is the chemistry
00:18:01
we used piece that three positively as well as all as a marker of like the receptor bearing arounds
00:18:08
we uh we distended the stomach with the balloon high physiological level then
00:18:13
we measured the activation of neurons from the distinction using c. fast
00:18:17
and what we found was that about thirty nine percent of the
00:18:20
map the receptor positive neurons were driven by the stench
00:18:24
so we had the far in the population of neurons that receive to it taking it or signals
00:18:30
then we perform an experiment where we selected pretty selected a
00:18:35
dose of weapon that had no intake inhibitory effect
00:18:38
a dose of this tension that had no intake inhibitory act deliberately the question was
00:18:44
if we presented these otherwise ineffective still really in combination with
00:18:48
the interact and and and and and amplify each other
00:18:52
so this is the the vehicle condition this is the uh the uh the dispensing condition this
00:18:58
is the latin condition or priest selected to have no effect and this is the combination
00:19:03
what you see is in combination with to interact producing a significant reduction
00:19:08
so that's also a that's provided support for the idea that there was
00:19:12
an interaction but we sought to take it a step further
00:19:15
the logic we applied here was the follow if we could reduce weapon signalling
00:19:21
specifically just of this population of neurons into really inflected signalling in
00:19:26
the rest of the braille alone and slapped interceptors all
00:19:28
of the brain as as many of you know the emphasis is but not type of logic let the receptive
00:19:34
um then we we could we could test the hypothesis that if we reduced latency
00:19:39
when using an s. h. r. ne delivered by and i mean these narrows
00:19:44
the hypothesis would be but by reducing clapton signalling we should
00:19:48
attenuate the intake inhibitory effect of g. i. signal right
00:19:52
so to evaluate that so to evaluate that we um use uh
00:19:57
exotic the c. c. k. which is known to reduce feeding
00:20:01
we gave it to these two groups had to had yet to receive either a
00:20:05
the the scramble control with the s. h. arnie for the lap interceptor
00:20:09
we did that and then we get number two different viruses and then we came back and we
00:20:13
reexamine their response to a an i. p. injection of of fifty k. four weeks later
00:20:20
i mean animals that received the scrabble control they continued to reduce
00:20:24
period take a response to to the c. c. k.
00:20:28
but the animals with partial this is the two piece your so we didn't
00:20:32
achieve a complete not then we were reproduced of forty percent market
00:20:36
and and even with a partial knocked out of being slapped a receptive with all the other latin signalling alone
00:20:43
b. c. c. k. was no longer able to significantly reduce and in fact enviable condition
00:20:49
the black or which represents the consumption of shoulder the animals over
00:20:53
consume shoulder as a function of the reduced lap and signal
00:20:57
that's consistent with the measure of wouldn't take that we may in
00:21:01
other parts of the experiment so here's the violent action
00:21:04
animals are maintained on chow for this period of time and their
00:21:07
tradition transition to high fat diet at this point in time
00:21:11
so during the chaff plays a letter receptor knocking on animals are i over eating
00:21:16
chow and when their transition to high fat diet or overeating high fat by
00:21:21
the result of this over in results in an increase in that uh possibly shown human body weight
00:21:28
you can set here shows the dissection of the fat cats a post holes the oppose that
00:21:35
not shown here is an assessment of energy expenditure there was no
00:21:39
evidence that energy expenditure was affected by this in the collection
00:21:43
so the increase in buying weight that we observe is driven by an increasing heating
00:21:48
and we assert that the increase in painting is at least partially explain why or reduction in sensitivity to
00:21:54
got signals will give you one more example and then transition to another part of the tall
00:22:02
so these are this i'm gonna now talk about the interaction between a bagel processing i'll
00:22:08
bagel after processing and isn't yes neurons and another input the t. cells to see
00:22:13
this is an artsy toasted positive x. along that's making
00:22:18
cinematic contact on and then it yes no so
00:22:21
the source of this article to positive projection is cells
00:22:26
in the cabin should you just make articles
00:22:29
and so here we see a tired in high drops a lace
00:22:33
positive the blue stain it yes in wrong and enclose
00:22:38
opposition to with this little beaded black isn't articles in fibre
00:22:43
and it's like selective physiology before by jim peters
00:22:47
he ended up seats also to the bass you stimulated the solitary track and what he determined was in the
00:22:53
presence of boxing toes and the normal excited toward dry but this big laugh and here was impossible
00:23:00
no this amplification is clear at the level of a lecture physiology but not clear
00:23:05
to level of behaviour so we go on to the valley with that
00:23:08
the next piece of that puzzle was to determine whether eating a meal would actually
00:23:13
give rise to an increase in nazi toes and delivery to these cells
00:23:19
and that's what we evaluate here we had an animal self to assume either nothing
00:23:24
or twelve m. l.'s although uh ensure diet that had fat and sugar
00:23:28
and we uh then dissected the tissue this is the this was the methodology we
00:23:33
determine that simply console way that meal increase datsun toes unavailability it is portable
00:23:41
no not the last analysis which is something that we've published relatively recently
00:23:45
again utilise is the s. h. r. ne idea knocking
00:23:49
down a partially the oxen toes interceptors uniquely expressed
00:23:54
in the ninety s. and again like the lap receptor knocked down or logic is as follows
00:23:59
that we know that that uh by consuming food and calories
00:24:04
there would be intake inhibition we hypothesise that the intake inhibitory effect of ingested
00:24:09
calories would be reduced by knocking their uh article from receptor segment
00:24:15
so here's one evaluation of that in the control animal as normal controls receptive signalling
00:24:21
do the animals or manipulate in the following way the consumers a control no when sure
00:24:26
seven hours of which of ensure or twelve and also should
00:24:30
ensure what you think is a calorie related reduction
00:24:34
in stealing that is obvious and a half an hour and purses for an hour and a half
00:24:39
simply by knocking down the articles receptor there's no longer statistical intake
00:24:44
inhibition that's observed that one or one and a half hours
00:24:48
and the only colour workload that's capable of reducing intake at the half hour is the high load not the norm
00:24:54
not to further evaluate the idea that reducing articles and signalling this for the brain with a
00:25:00
couple of part would would would attenuate the normal intake inhibitory effects of got signalling
00:25:06
we overnight deprive these animals which would generate a a greater motivation to
00:25:11
console r. and then determine whether that that the amount of
00:25:15
the everything was greater in the we hypothesise that would be greater
00:25:19
me animals with reduced articles and signalling and in fact
00:25:23
this is a significant increase yeah and at conception as a function of reduced signalling
00:25:30
now wanna make a transition from uh from the normal control of the d.
00:25:35
to the use of uh of tools that the very first
00:25:39
slide describe the need to create tools to treat obese
00:25:44
so we now know all their of the surgical approach there are
00:25:48
and there's the development of a variety of of former gunther
00:25:51
the former got therapy that are so these are are for drugs that are approved by
00:25:56
the f. d. a. in my country and i'm gonna focus on one of them
00:26:00
and this one uh we're retired at at the dos that's it's
00:26:04
been used to treat obesity it's called sex end up
00:26:07
this is a wrong acting uh agatha video p. one reset
00:26:13
and we have determined and publish that it's side of
00:26:16
action even though it's given peripherally isn't the sentiments
00:26:20
we've we've determined that in several studies one that that selectively cuts
00:26:26
the vehicle effort and the animals still suppresses it's meeting
00:26:30
and true we don't ever we are g. o. p. receptor antagonists directly to the brain
00:26:35
and that and the minutes the effect of the perfunctory so we believe that
00:26:40
the the history but is acting on central g. o. p. receptive terminals
00:26:46
and now i guess the activation of those terminals by the normal consumption of which i try to
00:26:51
show you earlier is activate central geo piece to
00:26:55
stop any gauges the inductance realise that
00:26:58
this is exaggerated we talked about intelligence really it's okay so ah i wanna i wanna uh
00:27:06
provide a context work for the us by comparing um by comparing these these uh
00:27:13
these labels or or or wrong this long sit there this one belongs here and
00:27:18
use the the or from then on and so what what we observed here
00:27:22
is that if you only those are forced to reduce their intake by being on
00:27:27
a ah a very low calorie diet that's the sum you turn the
00:27:31
and they lose weight not shell uh and we simply asked what's the
00:27:35
impact of reducing their way on their interest in eating from
00:27:40
and not surprisingly what you observe is when they're reexamined uh at the
00:27:45
end of the uh the dietary constraint or one year later
00:27:49
is that they are clamouring your as a function of losing weight and that their desire to e. is great
00:27:56
not shown ah would be the expectation that they're that they're fullness is declined
00:28:03
here by contrast is an evaluation of the g. o. p. ah receptor at
00:28:09
a at a nest of your good tied it to different houses
00:28:12
given to humans and an evaluation of the impact of this treatment on holder ratings
00:28:18
unanswered time and and i like the direction of the effect of weight loss
00:28:22
getting these drugs which we determine x. on the central nervous system actually
00:28:27
reduces the sense of older and increases the sense of subtle
00:28:33
so when the very last for the top no oh i wanna move back to the part of
00:28:38
the talk that we are i began and that was how compelling the fruit environment is
00:28:44
how the compelling nature of wood environment has to
00:28:47
do with the activation of central circuit
00:28:51
including circuits that are involved in pleasure circuits that are involved in action
00:28:57
so here is a a stimulus for some of this may be
00:29:02
the one that's no trouble for me it's not but
00:29:05
well everybody's gonna hand here tape reflected in this window
00:29:09
we know from the atom awry studies and we know from the pet studies that looking at this is
00:29:15
the activator range of places right it's even gonna sleep i give rise to discussion told him
00:29:23
so i just want to point out that are that they are there that that these fruit which we
00:29:28
would call energy dance and pleasurable we like them
00:29:33
they give us pleasure that positive don't value
00:29:36
we walked down that means that we're willing to work to take in them
00:29:41
yeah and in addition the cause us to learn how and where to
00:29:46
efficiently find them again i'd call this food seeking or repetitive behaviour
00:29:51
so i'm gonna describe enough final slides an analysis of the neural
00:29:56
circuits that can that can be activated to inhibit these response
00:30:03
so this is a a study that's uh our rad study done in in
00:30:07
the lab um and we've done this study with injecting a a another
00:30:13
another agonies of the g. l. p. one one receptor directly into
00:30:17
sites within the braided express the g. o. p. wanders up to realise
00:30:21
there are for the expression of g. o. p. one receptor
00:30:25
in that balance and the power of intruders down as we've done it in the mid mid dollar we don't and the parks
00:30:32
and so let me describe the power so these two environments represented
00:30:38
environments right there simply coded by as green or or purple
00:30:43
but in fact they vary in numerous ways one has a smooth or one
00:30:46
of the raw floor one as stripes one has horizontal one is vertical
00:30:50
i'll just accept that for the moment and this is about what i referred to before normal movie
00:30:56
simply consuming food in an environment changes the valence of that environment and
00:31:02
and and and resulting you're wanting to return to that and for
00:31:06
so if you get enough where we put an animal i mean i didn't around what choice how much time would you wanna spend on
00:31:14
the green side and on the purple side and we so we
00:31:17
create these environments of the animals no preference or equivalent preference
00:31:22
so no preference at the beginning than we begin training we associated
00:31:27
farm animals a high fat high sugar diet in the green
00:31:31
side for other animals to counterbalance it on the opposite side and
00:31:35
uh then a low fat diet on the opposite side
00:31:39
we do this multiple times and then after the training we now ask
00:31:43
again the question how much time you wanna spend on either side
00:31:47
and when we trade the animal with vehicle yeah well shows that
00:31:51
now it's spends twenty five percent more time on the side
00:31:55
of the environment that the animal that consume energy dense from
00:32:00
however if before the animals given this choice post train
00:32:05
we don't ever twenty five meg ryan's of uh of extending for to this place within
00:32:11
the break again we don't just three different times we get inside the brain
00:32:16
the animal fails to demonstrate the preference meaning that
00:32:20
despite what is learned because to control animals
00:32:23
have learned is intended despite what it has learned the animal doesn't display foot city
00:32:29
but the connection between the pleasures of the consumption and the
00:32:33
environment is blocked another paradigm call progressive ratio responding
00:32:40
it's a pat on that we used to evaluate fruit
00:32:42
heating motivation and by feeding motivation paradigm here is
00:32:47
yeah animal presses a lever to paint we should repellent forty five milligrams should
00:32:52
and what's progressive about progress of racial is to get the first colour depresses want
00:32:57
and then get each successive want us to work progressively harder
00:33:04
so that we we trained animal up then we had
00:33:07
given me the vehicle or two different doses of uh the g. o. p. was up to add interest
00:33:12
what we observed is just to leverage your peers apparatus
00:33:16
it either goes to one side within the brain
00:33:20
reduces the animals will be used to work for sure that up the last two slides of the talk
00:33:29
shift the focus to humans and try to make an analogy between what i just described for well it's like
00:33:36
so this is just say this is the same as the more i
00:33:39
handed on these of data from this group and the other ones
00:33:43
and uh also we have to stop groups of humans those little beach those are the type two diabetes
00:33:50
oh and they're looking at images of energy dense foods and energy nonsense fumes
00:33:55
and the the the energy dense foods or increasing relative to the risk the butler change
00:34:01
to the energy not dance fruit increasing but slow to a range of sites within the brain
00:34:06
began solo this try a them or before local cortex that we had observed before
00:34:12
however if they are treated peripherally er system likely with extended for the same g. o. p. result
00:34:18
to draw that that i that we see we another said determined penetrates the brain axon rain
00:34:25
then yeah the more i response to the energy dense tasty food images
00:34:31
is significantly reduced and then uh in the final data slide is a very recent data
00:34:38
that are examining the same kind of uh uh energy dense food images
00:34:44
palatable food response at m. r. i. response responses in humans
00:34:49
here the variable is not a drug treatment but another strategy
00:34:54
to treat obesity in that it's very attic surgery
00:34:57
so these patients have received gastric sleeve on and their value waited
00:35:03
in the scanner before surgery and twelve months have to search
00:35:08
and again they're confronted with these images of energy dance to what
00:35:12
you observe here is the significant reduction in the blood flow
00:35:16
change as a function of the surgery now what does this or do we do it gives rise these alterations yeah
00:35:22
uh in brain processing of of tasty food images well that's on the sixty four thousand dollar questions
00:35:29
um because ideally uh we would like to understand the bases of the barry attic surgery
00:35:36
so that we could treat humans with substitutes for that what non
00:35:39
surgical so i am by by and by just the reiterating
00:35:45
what i've tried to describe and and maybe adding one more thing
00:35:48
are hyper fey just riding obesity i think that's incontrovertible
00:35:53
oh and that hyper fate is real is resulting
00:35:56
from a prepared bright we've had we evolved
00:36:00
during um no many yeah i'll uh energy scarcity and that developed
00:36:05
a variety of circuitry is within our brain but facilitated he
00:36:09
opportunistic when um there's no question that energy dense fruit or
00:36:15
fruit we describe with human terms it's sweet or fatty
00:36:20
and the reason why we we prefer such foods or they had directly positive is
00:36:25
they projected delivery of calories and so uh i describe
00:36:30
the fact that normal uh intake innovation what's
00:36:33
i describe it normally taken of inhibition ah engages
00:36:37
a set of sorts including a of those
00:36:40
uh in a nucleus of the solitary track and projections to burn
00:36:45
i'd i believe the anti obesity drug therapy particularly the
00:36:48
g. o. p. drops or acting on similar circuits
00:36:52
and further but in addition to reducing the amount console
00:36:56
but they said you're basically drugs are impacting upon atomic processing is
00:37:01
the root of all in food seeking and feeding more
00:37:05
uh clearly drug therapy surgical approaches um are one strategy but there
00:37:11
are other strategies and clearly nestle is pursuing some others
00:37:14
including route reducing the capricorn work consequences of eating sugar intervening fat
00:37:21
and then on explored but something worth pursuing is trying to identify ingested nutrients
00:37:28
that may have uh the ability to elevate and that in those levels
00:37:32
of to tidy signals that may and dodging thusly activate inhibitory pathways
00:37:37
so with that i i and then and thank the people in my lap and collaborators that have generated the data like
00:37:53
oh i wish i experiment
00:37:59
so as a nation we have to see the structure issue but uh which is which
00:38:12
so it's just it's just the same circuit switched roles reduced picture different for instance gift secret
00:38:21
yeah so uh uh so the east right um and
00:38:26
so the the dolby neurons in the brain
00:38:29
uh and they're projections to both dorsal and ventral strident and
00:38:33
that the down screen circuits from them or exactly
00:38:36
the same circuits that are activated by other rewards these we would call natural words
00:38:43
and then we have drug rewards like cocaine morphine itself
00:38:48
so so there is so it's high calorie intake
00:38:54
well i it's called i think this is this is another one of these big questions it's been out there and uh
00:39:01
i i truly believe that are that there has not really been an adequate analysis
00:39:07
it's again a in in much the same way that david has asserted
00:39:11
people including women who runs the national institute of drug abuse in the united states
00:39:17
uh has just started on multiple occasions that in fact these are the scenes it up
00:39:22
again you hear this time and time again and perhaps you begin to leave it
00:39:26
but i think it's that i think that there's a range of data that strongly disagrees
00:39:32
with the idea that fee that that obesity can be understood as an addiction to
00:39:38
from a speech we get used to c. e. to just get discussed stuff
00:39:50
uh i very question actually i was wondering what to serve the relationship or some additional folks interesting
00:39:56
i moved them on stressing exactly actually if this is also something that
00:40:00
can this kind of course we can have an impact of remote
00:40:04
oh yes uh there uh as you as you're probably aware actually
00:40:08
tells it is a new heart uh had come out
00:40:12
um yeah there are a variety of other trials and you win trials are underway
00:40:18
uh i think many have been published already that involves
00:40:22
attempts to you to do ever actually closer to the brain via nasal delivery
00:40:27
um and uh it's being pursued for improving our uh the uh
00:40:33
uh improving the symptoms of what is what is so
00:40:36
don't to facilitate social behaviour it's being pursued by the uh
00:40:41
prayed really foundation old for its social impacts and forwards
00:40:46
would it take impacts and it's it's being put pursued in the context of stress anxiety as well
00:40:51
so more hate to see who can impact is kind of different collector pottery
00:40:57
recognition for example i i missed can we use actually chosen to
00:41:01
a sort of server surveyed marker or more group direction for
00:41:06
in order to see or or more uh up as it impacts mood plus
00:41:12
um i i would see no no no i would have no objection to to do such a marker
00:41:18
i think you know that how you how would you do that with respect to human study that would be quite difficult
00:41:25
but in animal studies i think it's certainly be a that's the territory to to actually to see
00:41:33
yeah yeah in question here counted in that actually aesthetics university after am
00:41:41
i am interested to hear your thoughts i mean bearing in mind the topic of
00:41:45
this symposium which is that i actually it's in carbohydrates if you think there
00:41:50
type faction circuits or overlapping high l. circuits and heart
00:41:53
race they're controlling intake of i personally chants
00:41:57
meg so so the at the at the idea the
00:42:00
idea that should the treatments might have impact on
00:42:04
oh and uh a different mecca nutrients is a is an idea that's been around for a long time i mean
00:42:10
uh that is been that that there have been a various publications that have pursued it
00:42:15
um but but i but i believe there that that uh that that it despite
00:42:20
some of the publications and despite some of the conclusions if you want
00:42:24
i think it's a bit better logically very challenging to do such work
00:42:29
oh where do you present individual mac or nutrients uh mike and mike macro nutrient
00:42:35
or you presented a combinations of then in the form of pepperoni and cookies
00:42:41
uh it's not the logically distinguishable and um one of my
00:42:45
my close friends and colleagues use weren't a lot
00:42:48
of work in this area our movie is the current uh president of the u. b. c. d. society
00:42:54
who has done a lot of work and syria's a it is certainly introduced
00:42:58
to certain question mark in my mind about the ease with which
00:43:02
one kid could pursue such question yeah obviously be be clear cool question it is might there be
00:43:09
a separate subsystem within the brady you could for rick it's carbohydrates eating in another one
00:43:16
ah that is the pits c. t. i. seems like a a tricky question but i'm i'm not so sure that uh
00:43:22
yeah but it's exists yet to support such segregation if you hadn't please
00:43:28
ah i don't ask you very nice question i'm sure you've used words and if you can swoops several times
00:43:35
i would suggest to me that on results obtained was sugar
00:43:39
helmets would not be obtained sugar solutions electro well i
00:43:44
i i i don't know the answer to that because the
00:43:48
ease you know it's clearly these commercially need boxes
00:43:53
can deliver either pellets or lover solution but ah of course
00:43:57
this study's data and where people have been very
00:44:01
well it's okay because your solution is to sell so mechanism i actually i actually address that question
00:44:14
okay do you have any speculation about why we have our
00:44:18
reward system to eat for touch with ah froze
00:44:22
box something like for each doesn't if oxide things get fairly originally people seem to think
00:44:29
for such a good thing to a right i'm sorry john spectrum from a shape
00:44:36
well john uh i know you you know more about the uh
00:44:40
about about obesity genetics and and and uh ideas related to
00:44:45
ah the the impacts of evolutionary pressures
00:44:50
on on development and it impacts on under system that night
00:44:54
but my answer to your question would be that the perspective that
00:44:58
i would take is that uh the brain was shaped
00:45:03
by uh as i describe before by by relative food scarcity
00:45:08
and under that condition and under the the the biological pressure
00:45:13
to lately liturgy balance in order for individual survival and nodded at at at
00:45:18
a good energy for reproduction it there was a premium upon eating opportunistic
00:45:24
i'd also search that uh on like or ability now to to firmly detergents foods that are
00:45:30
low cost and low consequence at least it from the perspective of of uh predation
00:45:36
oh that that was not the case back way back when and uh that
00:45:41
as at that as the sensory qualities the uh so phallic sensory qualities
00:45:48
that uh that it more most of that's we is which one was about that
00:45:52
or are are rewarding i would assert as they
00:45:56
predict the delivery of energy dense from
00:45:59
then right yeah and i i would assert that that connection we do every
00:46:05
of oh signals process but the cost of tori and other or sensory
00:46:09
that's the jews and the connection of that to the central nervous system made to that tried
00:46:15
about now what you were talking about now as it is in in a certain sense
00:46:20
uh taking the taking the the pride perspective where we wanna modified
00:46:26
diets we want to facilitate the consumption of certain clean if
00:46:30
it's deep facilitate the consumption of other kinds of foods
00:46:35
e. the question is you know how might be able to reshape that i think that's
00:46:40
and it's that with the plane out of a mole any uh or certainly over longer units
00:46:45
of time we have actually pushed if you're good you sure it suppose to switch right
00:46:53
yes but it also from boston so more and more specific
00:46:57
question of their intriguing it between opposite oh see handy
00:47:01
for so supposing you are cuter halfway see across purchase orders so so in terms of for it you
00:47:09
know just social connection with articles you know we we know for an hour researcher that you know that yeah
00:47:13
it benefits of social e. d. i. y. stuff that's
00:47:17
our community preparation of family means something i hate
00:47:21
kept showing or if it's our research arteries that usually i
00:47:26
literature focuses only on the arty invalid souls wonder
00:47:29
whether you know even in this province that's right but for you but somehow or people working if it
00:47:36
a fight sound i guess of a puppet show mechanism
00:47:40
maybe a history control aspects associated socially for
00:47:44
yes that's uh you know social behaviours r. e. l.'s row sort things that are going
00:47:50
to attack you know i was but i i really can't answer that question directly with respect
00:47:56
to articles but i i am aware of a public study by john de castro
00:48:01
where he you measure uh the impact of the
00:48:05
number of people you were eating dinner with
00:48:08
on how much you it indeed determined that the more people you with more food short question
00:48:19
thanks for the chair uh i want to try it out on that throw away from from right right at the end which was a fiction
00:48:27
and that association addiction and basically under his database
00:48:33
people don't have any increased risk of
00:48:35
either addictions i now i should i ain't tape stock or
00:48:41
that he controller i enjoy eating or i get clarify
00:48:46
that issue i think tonics fiction that have a large
00:48:50
oh wrong now problematic a true knowledge and
00:48:56
i well i will try and i would have to uh uh begin by saying that
00:49:03
i'm not a clinician and my my knowledge base uh on on drug addiction is is
00:49:09
a is more limited than mine mine knowledge based on on uh energy bounces
00:49:14
but ah um but first let me back qualifying the idea that they get through the baby out with the
00:49:20
bathwater and said that uh that that that addiction is
00:49:24
not an adequate explanation for b. c. re or
00:49:29
but i would be the first person to say that that we
00:49:32
talk about obesity we talk about it in the monolith picture
00:49:36
it is accumulating evidence the tears job types like um we don't know enough yet and
00:49:42
we know that there's a genetic basis we know that it's not mine agenda
00:49:45
we have to define what the particular genes or what combinations of g. zero
00:49:50
one thing is clear from some human current human literature
00:49:54
in from of parallel literature in animals is
00:49:57
that there are different uh let's say even feeder
00:50:02
types unknown members of the same species
00:50:06
so if we expand upon that ideas in other words and maybe some humans were
00:50:11
less sensitive to got sick in maybe some humans that are more sensitive
00:50:16
they don't make a pool of the of the environment and i
00:50:19
would certainly not real out the idea that there's some fraction
00:50:23
you are so compelled by by the environment and that that may
00:50:27
be interacting with stress or is it like history or
00:50:31
or or psycho pathology that maybe i'll uh yes
00:50:35
and the it repeatedly more diction like
00:50:38
but i do believe that yeah in the psychiatric literature there's
00:50:43
a set of criteria for defining what is addictive
00:50:47
i think if you apply those criteria to to feeding behaviour and overeating more generally it
00:50:53
fails to explain right she question but maybe for sake of to use it
00:51:02
i would like to see it just because it works
00:51:09
it's usually when we used to publish e. e. which is which is c. h. e. g.
00:51:18
it's you she started you it'll be something to do

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Conference program

Nutrition advocacy in action: the politics of sugar vs. fat
Marion Nestle, New York University, USA
28 Sept. 2017 · 9:27 a.m.
Fat and carbohydrate recommendations - Have they changed?
Barbara Schneeman, University of California, Davis, USA
28 Sept. 2017 · 10:14 a.m.
Promoting equitable health and wellbeing around the globe
Nancy Brown, American Heart Association, Dallas, USA
28 Sept. 2017 · 11:30 a.m.
Gut hormones and nutrition
Sir Stephen Bloom, Imperial College London, England
28 Sept. 2017 · 1:38 p.m.
Nutrition, metabolic health, cancer and NCDs
Elio Riboli, Imperial College London, England
28 Sept. 2017 · 2:27 p.m.
Infant and child nutrition and cognitive development
Wendy Oddy, Menzies Institute for Medical Research, University of Tasmania, Hobart, Australia
28 Sept. 2017 · 3:51 p.m.
Microbes, metabolism and autoimmunity
Ramnik Xavier, Massachusetts General Hospital, Boston, USA
29 Sept. 2017 · 9:06 a.m.
Lipid metabolism in high fructose fed humans
Luc Tappy, University of Lausanne, Switzerland
29 Sept. 2017 · 10:03 a.m.
Food, health and disease: The evidence and reporting the evidence
Dennis Bier, Children's Nutrition Research Center, Baylor College of Medicine, Houston, USA
29 Sept. 2017 · 11:11 a.m.
Deeper down the rabbit hole of data, analysis, and inference errors and suggestions for digging back out
David Allison, Indiana University School of Public Health, Bloomington, USA
29 Sept. 2017 · 1 p.m.
Neural circuits of food intake - is it all about calories?
Harvey Grill, University of Pennsylvania, Philadelphia, USA
29 Sept. 2017 · 1:55 p.m.

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