‫به نام خدا‬
‫‪1‬‬
CONTROL OF
FOOD INTAKE AND APPETITE
2
Fast forward 15 years to 2030
Humans are sicker than ever
Life expectancy has decreased and
productivity is down
What’s the underlying cause?
Obesity
3
Traditionally, a distinction has
been made between
homeostatic & nonhomeostatic
control of appetite and food
intake
4
Deviation from homeostatic control
physiologic
nonphysiologic
obesity
5
CENTRAL CONTROLS OF FOOD
INTAKE AND APPETITE
Coordination by the
Hypothalamus
6
The hypothalamus is widely recognized as the
“gate keeper”
in the control of food intake and appetite
7
the lateral hypothalamus as the
“hunger
center”
and
the medial hypothalamus as the
“satiety
center”
8
A network of
communication
among the gut,
pancreas, adipose
tissue, brainstem,
and hypothalamus
is well established
9
Additionally, further communication
exists between the
hypothalamus and higher cortical centers
pertaining to
food memory of food, with resulting
overall coordinated
control of food intake
10
Role of the Brainstem
is the main organ responsible for facilitating
the communication between peripheral signals
of food intake and hypothalamic nuclei
11
The arcuate nucleus
(ARC) is thought to be the
main hypothalamic
area controlling food
intake
12
Within the ARC, two groups of neurons are pivotal
in regulating food intake
One group of neurons
contains
neuropeptide Y (NPY), and
most of these also contain
Agouti-related peptide
(AgRP)
The second group is formed
by neurons containing
pro-opiomelanocortin
(POMC)
Activation of these
neurons
enhances food ntake
Activation of these
neurons
reduces food intake
(orexigenic)
(anorexigenic)
13
NPY
is the
most powerful
central stimulant of
appetite
14
Neuropeptides Implicated in the Control of
Food Intake
• Agouti-Related Peptide
• Cocaine- and Amphetamine-Regulated Transcript
•
•
•
•
•
•
Hypothalamic Releasing Hormones
Orexins
Melanin-Concentrating Hormone
Brain-Derived Neurotrophic Factor
Ciliary Neurotrophic Factor
Central Neurotransmitters
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PERIPHERAL CONTROLS OF FOOD INTAKE
AND APPETITE
Nutrient, hormonal signals from the
gastrointestinal system, endocrine
organs, and adipose tissue
all have essential roles in influencing
food intake and appetite
16
These peripheral signals target areas
of the hypothalamus to regulate
appetite
They include signals conveying a
feeling of fullness (satiety signals)
and
hunger (orexigenic signals)
17
These signals can control
meal size
&
meal number
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Neural Signals
Orosensory and Optic Stimuli
Orosensory and optic stimuli
provide the brain with
sensory information regarding the
nature of food
These stimuli include
appearance, taste, smell, and textural stimuli
19
The information is
used by the brain to decision
to eat or not eat
to continue or to stop eating
20
Gastric Distention
Volume-related
postprandial gastric
distention results in
satiety during a meal
bariatric surgical
21
Nutrient Signals
Most nutrient signals exert their effects
on the gastrointestinal
system and the brain and induce the
secretion of gastrointestinal
hormones and appetite regulation
22
Gut Hormones
• the largest endocrine organ
• secretes more than 30 different regulatory
peptide hormones
• digestion and absorption
• affect short-term feelings of hunger and
satiety
23
These hormones are
the subject of extensive
research, given their
potential as
physiologic antiobesity
therapies
24
Cholecystokinin (CCK)
• It is released postprandially
• slowed gastric emptying
• CCK reduces food intake
25
Ghrelin
• Increases appetite
• “hunger hormone”
• considered as one of the most powerful
physiologic orexigenic agents
• increases food intake and body weight
in rodents
• Plasma ghrelin levels are also noted to
increase on weight loss (regain weight )
26
Peptide YY (PYY)
• released postprandially
• PYY administration decreases food
intake
• Obese patients demonstrate a blunted
postprandial rise in PYY
• PYY-based antiobesity agents are
currently under development
27
Glucagon-like Peptide-1(GLP-1)
•
•
•
•
reduces food intake
released postprandially
reduces gastric emptying
analogs of GLP-1 are used in the
treatment of type 2 diabetes
• currently undergoing clinical trials for
the treatment of obesity
28
Pancreatic Hormones
• major function is to control glucose
homeostasis (Insulin & Glucagon)
• pancreatic polypeptide and amylin, also
affect appetite ( are satiety signal and
reduces food intake)
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Hormones from Adipose Tissue (leptin)
• a circulating protein produced by adipocytes (fat
cells)
• is a signal from the adipose tissue to the brain that
reflects the state of energy stores
• increased by overfeeding
• absence of leptin lead to severe obesity
• Leptin acts on ARC LepR to stimulate
POMC neurons and inhibit NPY/AgRP
neurons to decrease food intake
30
Other Hormones
Thyroid hormones, gonadal steroids
and glucocorticoids regulate metabolic
rate, reproductive state and stress
responses, respectively
These processes rely on adequate
energy supplies. Therefore, it is not surprising that
hormones regulating these processes are also
involved in the
endocrine regulation of appetite
31
Signals from the Immune System
Anorexia or decreased food intake
during infectious,
inflammatory, and neoplastic disease
states is very evident.
Anorexia appears to result from the
action of cytokines in the brain
32
Hedonic Mechanisms
The word “hedonic” relates
to pleasant (or unpleasant)
sensations
visual, smell, and taste
signals can override
satiety signals to maintain
food intake
33
CONCLUSION
The regulation of food intake and
appetite occurs through
the integration of various
central and peripheral signals
34
These signals interact at the level of the
brainstem and hypothalamus
to produce an overall response of
hunger
or fullness
Additionally,
these neuronal networks are hugely
modified by other influences such as sensory
inputs, food memory, rewarding aspects
of food, and numerous environmental and
emotional factors
35
This modification is a
particular feature of modern
human eating behavior and
may underpin the dysregulation
of energy balance that is
responsible for the current
obesity epidemic
36
By means of ever-expanding
current research , it is hoped that
our understanding of the complex
and intricate signaling pathways
governing appetite control will
improve and pave the way for
better
antiobesity drug treatments
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