control of food intake and appetite is an interesting title in medicine specially in nutrition field.

1. Prepered By : Mohammad Ashraf Farahmand
2019:05:12

2.  CENTRAL CONTROLS OF FOOD
INTAKE AND APPETITE
 Coordination by the Hypothalamus
 Role of the Brainstem
 Neuropeptides
 Central Neurotransmitters
 Hedonic Mechanisms
 Mnemonic Representations of Experience with Food
 Endocannabinoids
 PERIPHERAL CONTROLS OF
FOOD INTAKE AND APPETITE
 Neural Signals
 Nutrient Signals
 Hormanal signal (Gut Hormones
,Pancreatic Hormones , Hormones from
Adipose Tissue , Other Hormones
 Signals from the Immune System

3. CENTRAL CONTROLS OF FOOD
INTAKE AND APPETITE
 Coordination by the Hypothalamus
 Role of the Brainstem
 Neuropeptides
 Central Neurotransmitters
 Hedonic Mechanisms
 Mnemonic Representations of Experience with Food
 Endocannabinoids

4. Coordination by the Hypothalamus
 Hyopthalamous ; “gate keeper” in the control of food
intake and appetite.
 Peripheral signals of energy balance may act directly
on the hypothalamus to control food intake,
 communication between the hypothalamus and higher
cortical centers pertaining to food memory and
rewarding aspects of food
 lateral hypothalamus “hunger center,”
 medial hypothalamus “satiety center.

5. The presence of a network of
communication
among the gut, pancreas, adipose tissue,
brainstem, and
hypothalamus

6. Role of the Brainstem
 sensing of energy balance and modulation of food intake
 dorsal vagal complex (DVC) is the main organ responsible
for facilitating the communication between peripheral signals
of food intake and hypothalamic nuclei
 DVC consists of :
 nucleus of the tractus solitarius (NTS)
 area postrema (AP)
 dorsal vagal nucleus (DVN).

7. Con ...
 Vagal nerve afferents: carry sensory information relaying
hunger and satiety from the gut directly to the NTS(increased meal
size and duration)
 AP receive metabolic signals of energy balance (e.g., hormones and
nutrients carried by the blood) directly(abscence of complete BBB)
 Efferent pathways : hypothalamus ↓→ DVN (modulates) ↓→
efferent
 vagal nerve activity → alter:
o gastric emptying, gastric motility, and pancreatic secretions.

8. Hypothalamic Nuclei Implicated in the
Control of Food Intake
 arcuate nucleus (ARC) :main hypothalamic area
controlling food intake( incomplete BBB allow
peripheral signals to gain access to the central nervous
system)
 Neurons within the ARC:
 1- neurons contains neuropeptide Y (NPY) and Agouti-
related peptide (AgRP)
 Activation: enhances food intake (orexigenic)
 2- neurons containing pro-opiomelanocortin (POMC)
and cocaine- and amphetamine regulated transcript
(CART)
 Activation : reduces food intake (anorexigenic)

9. Con...
 Axons from ARC (NPY/AgRP and POMC/CART, )
neurons project to other areas of the hypothalamus
 paraventricular nucleus (PVN)
o Destruction : hyperphagia and obesity in rats
 ventromedial nucleus (VMN)
 dorsomedial nucleus (DMN)
 lateral hypothalamic area (LHA)
 perifornical area (PFA)
o to modulate food intake.

10. Neuropeptides Implicated in the Control of
Food Intake
 Neuropeptide Y
 the most powerful central stimulant of appetite(ARP)
 Approximately 90% of NPY neurons coexpress AgRP
 Central administration of NPY enhances food intake in rats
 repeated daily injections of NPY into the hypothalamus result in chronic
hyperphagia and weight gain in these animals
 Ablation of NPY/AgRP neurons in mice leads to reduced body weight via reduced
food intake
 Y1 and Y5 receptors seem to mediate the orexigenic effect of NPY

11.  Agouti-Related Peptide/AgRP
 1- competitive antagonist of anorexigenic central
melanocortin receptors in the PVN
 increases food intake (12)
 2- Also action on orexin or opioid receptors

12.  Pro-opiomelanocortin and
Melanocortins:
 POMC is the precursor of α melanocyte-stimulating hormone(α-
MSH).
 αMSH binding to the MC4R acts to reduce food intake
 homozygous mutations in the POMC gene in humans result in early-
onset obesity
 Cocaine- and Amphetamine-Regulated
Transcript
 CART is coexpressed by most POMC neurons in the ARC.
 Central intracerebroventricular administration of CART reduces food
intake in rats

13.  Hypothalamic Releasing Hormones
 Corticotropin-releasing hormone(CTRH) and thyrotropinreleasing hormone (TRH)
are expressed in PVN neurons.
 both inhibit food intake
 Orexins
 Orexin A and B (OXA and OXB) activate G-protein– coupled receptors to
increase food intake.

14.  Melanin-Concentrating Hormone:
 MCH is an orexigenic signal expressed in neurons located in the
LHA
 Infusion of MCH in rats increases food intake and body weight
 Brain-Derived Neurotrophic Factor:
 BDNF is highly expressed in the VMN and acts via MC4R signaling
to reduce food intake

16. Central Neurotransmitters Controlling Appetite
and Food Intake
 Serotonin:
 produced in the dorsal raphe nucleus
 reduces food intake and body weight
 Norepinephrine:
 produced in the DVC and locus coeruleus,
 has differing effects
 on α2 receptors stimulates food intake,
 α1, β2, and β3 receptors reduces food intake

17. CON ...
 Dopamine
 inhibit food intake in the ARC and LHA
 orexigenic action in the VMN
 action of dopamine on D1 and D2 receptors reduces food intake
 stimulation of the D5 receptor is associated with reward pathways

18. Hedonic Mechanisms and Corticolimbic Pathways
Controlling Appetite and Food Intake
 visual, smell, and taste signals can override satiety signals to maintain
food intake despite neutral or even positive energy balance
 These sensory signals are conveyed from NTS in the brainstem to
corticolimbic reward centers implicated in appetite regulation
 Dopamine, serotonin, opioids, and norepinephrine have been implicated
as important neurotransmitters involved in signaling within this network.

19. Mnemonic Representations of Experience with Food
 Past experience with specific foods forms an important contributor to continued
consumption
 Orbitofrontal cortex (OFC), an area that receives converging sensory input in
the nonhomeostatic control of food intake.

20. Endocannabinoids
 shown to produce a dosedependent orexigenic effect
 This effect is thought to occur via modulation of reward
circuitry
 1- : Anandamide (AEA), derived from membranous
phospholipids
 2- : 2- arachidonoylglycerol (2-AG), derived from
triglycerides
 Endocannabinoids may also act directly on the
hypothalamus to exert their orexigenic effect.
 These substances are secreted by postsynaptic neurons
 act in retrograde fashion,

22. Peripheral Controls Of Food Intake
And Appetite
 Neural, nutrient, and
hormonal signals from
 the gastrointestinal system,
 endocrine organs,
 adipose tissue,
 and circulation all have
essential roles in influencing
food intake and appetite.

23. Neural Signals
 Orosensory and Optic Stimuli:
 stimuli include appearance, taste, smell, and textural stimuli
 Visual information , signals in the afferent optic fibers of cranial nerve I
 Gustatory, olfactory, and orosensory information →fibers of cranial nerves VII, IX,
I and V → brain important for taste, reward, flavor, and → mnemonic → dorsal
vagal complex, limbic system and OFC

24. Gastric Distention
 Volume-related postprandial gastric distention results in satiety during a
meal.
 Mechanoreceptors in the stomach wall sense stretch,volume, and tension
during a meal → afferent fibers of the vagal & spinal visceral nerves
 used in the management of severe obesity(surgery)

25. Glucose
 Glucose alters the firing rate of neurons in the ARC,
LHA, and NTS
 cellular influx of glucose alters the ratio of AMP to ATP)
within the neuronal cell
 1- ATP-dependent membrane channels that may
influence neuronal depolarization
 2- alter the activity of important nutrient sensing
enzymes (e.g., AMP-activated protein kinase)
 Some neurons (e.g., ARC POMC neurons) are excited
by glucose,
 others (e.g., ARC NPY neurons) are inhibited by glucose

26. Circulating Lipids
 Circulating lipids such as long-chain fatty acids (LCFAs) can alter
feeding behavior by directly activating central neural pathways
 intracerebroventricular administration of an LCFA (oleic acid) also
decreased food intake

27. Gut Hormones
 Ghrelin
 Peptide YY (PYY)
 Cholecystokinin (CCK)
 Pancreatic polypeptide (PP)
 Amylin
 Glucose-dependent
insulinotropic polypeptide
(GIP)
 Glucagon-like peptide-1, 2
(GLP-1, 2)
 Oxyntomodulin

28. Cholecystokinin
 CCK is synthesized in the I cells of the small intestine
 promote fat and protein digestion
 It results in gallbladder contraction, relaxation of the sphincter of Oddi,
somastostatin release, stimulation of pancreatic enzyme release, and
slowed gastric emptying
 afferent fibers transmit signals → NTS(central melanocortin system ) →
reduce food intake

29. Ghrelin
 Ghrelin is the only known gut hormone that increases appetite “hunger
hormone.”
 produced by the A-cells of gastric fundus
 Its other actions include increase in gastric motility and stimulation of
growth hormone release
 The metabolic effects of ghrelin include increased fat storage and
decrease in fat use
 Plasma ghrelin levels rise before meals and decline after eating

30. Peptide YY
 Peptide YY (PYY) is a member of PP fold family, which also includes
NPY and pancreatic polypeptide
 PYY is released postprandially
 release of PYY is augmented by dietary fat
 PYY administration decreases food intake in rodents and humans
 PYY may reduce food intake by decreasing ARC NPY levels via the ARC
Y2 receptor or via its effects on the vagus nerve
 it also delays gastric emptying.

31. Glucagon-like Peptide-1
 Enteroendocrine L cells → preproglucagon →
GLP-1 , GLP-2 , and oxyntomodulin
 GLP1 :
 released postprandially
 It is an incretin, which results in increased
glucose-dependent insulin release
 It also reduces gastric emptying and gastric acid
secretion
 inhibits glucagon release.
 reduces food intake
 oxyntomodulin
Despite semilarity ot GLP 1 , it increases energy
expenditure and
may suppress ghrelin release,

32. Pancreatic Hormones
 Insulin:
 Primary role ...
 Efect on apatite and satiety :
 Indirect : low blood glucose → increase in
food intake
 Direct : acts on ARC insulin receptors →
decrease food intake
 Glucagon:
 decreases meal size, and reduces overall
food intake and body weight

33. ...
 Pancreatic polypeptide :
 PP is secreted postprandially
 It delays gastric emptying and reduce appetite
 exerts its effects via acting on theY4 receptors in the ARC, in the AP, or via the
vagus
 Amylin:
 inhibits gastric secretion, delays gastric emptying
 It is a satiety signal and reduces food intake and body weight

34. Hormones from Adipose Tissue
 Leptin
 Produce in adipose tissue
 exerts its effects by acting on the leptin
recep tor (LepR)
 Leptin acts on ARC LepR to stimulate
POMC neurons and inhibit NPY/AgRP
neurons to decrease food intake
 failure of leptin to diminish appetite in
obesity is termed leptin resistance

35. Other Hormones
 Thyroid Hormone
 Thyroid hormone regulates basal metabolic state
 Hyperthyroidism is associated with increased food intake and decreased body
weight
 Gonadal Steroids
 In rodents, orchiectomy ;decreases food intake, ovariectomy ;increases food
intake
 Glucocorticoids :
 generally stimulate food intake and weight gain