Control of food intake and appetite
- 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