Appetite regulation


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What controls our appetite or suppresses it? How can we use this knowledge to eat better?

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Appetite regulation

  1. 1. DIET AND NUTRITION Appetite Regulation By Dr Madhumita Sen
  2. 2. Learning Objectives In this lesson the student will learn  What is appetite  Brain control of appetite  Hormones that regulate appetite, and their basic modes of action.
  3. 3. Appetite  Appetite is the desire to eat food, felt as hunger.  Appetite exists in all higher life-forms, and serves to regulate adequate energy intake to maintain metabolic needs.  It is regulated by a close interplay between the digestive tract, adipose tissue and the brain.
  4. 4.  Appetite is different from hunger.  Hunger is our physical need to eat.  You can want to eat but not need to eat (for example, wanting to eat dessert after a big meal).  Or you can need to eat but not want to eat (for example, losing your interest in food when you’re stressed).  When we lose stored fat, our body mounts a major response to conserve energy and boost appetite, defying further weight loss and encouraging regain.  Note: Prader-Willi Syndrome and Hypothalamus.
  5. 5.  When stressed, appetite levels may increase and result in an increase of food intake.  Decreased desire to eat is termed anorexia,  Increased appetite is called orexia  While polyphagia (or "hyperphagia") is increased eating.  Dysregulation of appetite contributes to  anorexia nervosa,  bulimia nervosa,  cachexia,  overeating, and  binge eating disorder.
  6. 6.  The hypothalamus, a part of the brain, is the main regulatory organ for the human appetite.  The neurons that regulate appetite appear to be mainly serotonergic.  The hypothalamus senses external stimuli mainly through a number of hormones such as leptin, ghrelin, PYY 3-36, orexin and cholecystokinin; all modify the hypothalamic response.  They are produced by the digestive tract and by adipose tissue (leptin and adiponectin).
  7. 7.  Systemic inflammatory mediators, such as tumor necrosis factor-alpha (TNFα), interleukins 1 and 6 and corticotropin-releasing hormone (CRH) influence appetite negatively; this mechanism explains why ill people often eat less.  In addition, the biological clock (which is regulated by the hypothalamus) stimulates hunger.  Processes from other cerebral loci, such as from the limbic system and the cerebral cortex, project on the hypothalamus and modify appetite.  This explains why in clinical depression and stress, energy intake can change quite drastically.
  8. 8.  Appetite is regulated by a complex system of central and peripheral signals which interact in order to modulate the individual response to nutrient ingestion.  Peripheral regulation includes 1. satiety signals and 2. adiposity signals, while  Central control is accomplished by several effectors, including the 1. neuropeptidergic, 2. monoaminergic and 3. endocannabinoid systems.
  9. 9. Hormones in Appetite Regulation Calcitonin Released in response to gastrin and changes in serum calcium levels Secreted by cells in the thyroid, GI tract, and pancreas A complementary signal responsible for fine tuning the eating process
  10. 10. Amylin A partner hormone to insulin, released after meals Secreted by the pancreas It slows the emptying of our stomach and suppresses glucagon (glucagon raises blood sugar)
  11. 11. GLP-1 Released when blood glucose levels are above the norm Secreted by cells of the gut in proportion to the amount of energy ingested Stimulates insulin and amylin secretion, may assist in signalling the brain to stop eating
  12. 12. Leptin Released with low calorie intake and low body fat levels. Secreted by fat cells Low leptin means a slower metabolism and drive to increase food consumption. Administering leptin analogs in humans is ineffective for appetite suppression. Leptin exists to prevent starvation, not to lose weight. Only when leptin is provided along with amylin, slight fat loss may occur
  13. 13. Gastrin Released when food enters stomach, protein dense foods are the most potent stimulator of gastrin Secreted by cells in stomach/small intestine Initiates the digestion process
  14. 14. Secretin Released when acids reach small intestine Secreted by cells in small intestine Produces pancreatic fluid, inhibits gastrin release, and enhances effects of cholescystokinin
  15. 15. Cholecysto kinin (CCK) Released when protein and fat enter the small intestine Secreted by cells in small intestine Signals pancreas to produce enzymes, inhibits gastrin, stimulates gallbladder contraction, and triggers satiety in the brain
  16. 16. Gastric inhibitory polypeptide (GIP) Released when food enters small intestine Secreted by cells in small intestine Enhances insulin release, inhibits gastric secretions and motility Motilin Released when bicarbonate is dumped into the small intestine and between meals/when fasting Secreted by cells in small intestine Promotes muscle contraction of GI tract, and when released between meals, you’ll notice borborygmus (growling stomach)
  17. 17. Somato- statin Released between meals to reduce digestive activity Secreted by stomach, intestine and pancreas Slows gastric emptying, reduces GI muscle contractions and blood flow to gut PYY 3- 36 Released in the hours following a meal, presumably to suppress appetite Secreted by the small/large intestine Inhibits stomach motility while increasing water and electrolyte absorption in the colon. May also suppress pancreatic enzyme secretion. Obesity seems to be a PYY 3-36 deficient state
  18. 18. Ghrelin Released in response to low food intake/fasting Secreted by cells of the stomach, pancreas, placenta, kidney, pituitary and hypothalamus Stimulates release of growth hormone to encourage eating and acts to regulate energy balance.
  19. 19.  Adiponectin  Adiponectin, also called adipocyte complement- related protein is a 244-amino acid protein secreted from adipose tissue.  The plasma concentration of adiponectin is inversely correlated with adiposity in humans.  Studies show that treatment with adiponectin can reduce body weight gain, increase insulin sensitivity, and decrease lipid levels.  Thus adiponectin, as well as increasing energy expenditure, may also provide protection against insulin resistance and atherogenesis.
  20. 20.  Resistin  Resistin is also produced by adipose tissue and appears to increase insulin resistance.  Circulating resistin is increased in obese people and falls after weight loss.  Although resistin may contribute to the development of insulin resistance and diabetes in obesity, its role in the pathogenesis of obesity remains to be defined.
  21. 21.  Pancreatic Hormones  Insulin  The pancreatic hormone insulin was one of the first adiposity signals to be described and, like leptin, is positively correlated with long-term energy balance.  Plasma insulin concentrations depend on peripheral insulin sensitivity, with visceral fat being a key determinant.  However, unlike leptin levels, which are relatively insensitive to acute food intake, insulin secretion increases rapidly after a meal. Insulin is an anabolic hormone and increases appetite.
  22. 22.  Pancreatic polypeptide  Pancreatic polypeptide (PP) is a member of the PP-fold family of peptides which also includes peptide YY (PYY) and NPY  PP is primarily produced by cells at the periphery of the islets of Langerhans but is also secreted by the exocrine pancreas and distal gastrointestinal tract.  Plasma PP concentrations show diurnal variation, with lowest levels in the early hours of the morning and highest in the evening.  PP directly reduces appetite via the brain.
  23. 23.  Oxyntomodulin  OXM is released in proportion to calorie intake from the L cells of the small intestine.  Both central and peripheral OXM acutely reduce food intake.  The actions of both GLP-1 and OXM on food intake may be mediated by the GLP-1 receptor.  OXM may also reduce appetite by inhibition of ghrelin release.
  24. 24. Central Regulators of Appetite  Hypothalamic Neuronal Pathways Regulating Appetite:  Despite wide daily variation in food intake and energy expenditure, for most individuals, body weight remains remarkably stable over long periods of time.  For this, food intake and energy expenditure must be constantly modulated and balanced.  The hypothalamus is essential for the regulation of appetite and energy balance.
  25. 25.  The brain initiates responses to feeding even before the ingestion of food.  The very sight and smell of food stimulates exocrine and endocrine secretions in the gut as well as increasing gut motility.  Ingestion of food stimulates mechanoreceptors leading to distension and propulsion to accommodate the food.  As the food is propelled through the gut regions of the intestines secrete various hormones that circulate to the brain and impact hypothalamic responses
  26. 26.  Neuronal circuits within these regions of the hypothalamus signal using specific neuropeptides, for example,  corticotrophin-releasing hormone (CRH/POMC),  thyrotropin-releasing hormone (TRH),  neuropeptide Y (NPY),  brain-derived neurotrophic factor (BDNF),  orexin, and  melanin-concentrating hormone (MCH).  Cocaine and amphetamine regulated transcript (CART)
  27. 27. Orexigenic Pathways  Neuropeptide Y, NPY  NPY is expressed throughout the brain with highest levels found in the hypothalamus.  NPY is one of the most potent orexigenic factors produced by the human body.  Neurons that co-express NPY and agouti-related peptide (AgRP) stimulate food intake.
  28. 28.  Agouti-related peptide, AgRP  AgRP is a protein, a member of the central melanocortin system, which in addition to AgRP, includes αlpha-melanocyte stimulating hormone (α-MSH).  AgRP and NPY have evolved to ensure the signalling of hunger during food scarcity and to enable the body to endure long periods of negative energy balance.  It increases appetite.
  29. 29.  Melanin-Concentrating Hormone, MCH  MCH is an important orexigenic (appetite stimulating) hormone.  In addition to modulation of feeding behaviors and energy expenditure, the MCH system has been shown to be involved in affective disorders such as anxiety and depression.  MCH system is important in the modulation of stress responses.
  30. 30.  The Orexins (A and B)  The orexins are also called the hypocretins.  They are shown to increase food consumption  In addition to increased feeding behavior, central administration of orexins increases wakefulness and suppresses REM sleep.  These latter observations demonstrate that orexins play a causative role in the regulation of sleep- wake cycles.
  31. 31.  Galanin, GAL  GAL is expressed in the gut and the brain with wide distribution throughout the hypothalamus  It is involved in learning and memory, mood disorders and anxiety.  The primary function of GAL is to restore carbohydrate balance, through behavioral and metabolic actions by increasing the hunger for sweet foods.
  32. 32.  Endocannabinoids  The appetite-stimulating effects of marijuana (Cannabis sativa) have been known for a long time.  Several studies have indicated that administration of cannabinoids stimulates food intake in animal models.  Appetite is increased by both peripheral and central administration of anandamide, one of the major endocannabinoids.
  33. 33. The Anorectic Pathways  POMC-Derived Melanocortins  The POMC-derived melanocortin peptides include α-MSH, β-MSH, γ-MSH and ACTH.  The melanocortin system has been shown to be critical in the regulation of food intake and energy expenditure.  The melanocortins, α-MSH, β-MSH, and ACTH directly inhibit the intake of food.
  34. 34.  Cocaine- and Amphetamine-Regulated Transcript, CART  The cocaine- and amphetamine-regulated transcript (CART) peptides are neuroendocrine peptides involved in feeding behavior, drug reward systems, stress, cardiovascular functions, and bone remodeling.  CART peptides are anorexigenic (decrease appetite)
  35. 35.  Galanin-like peptide, GALP  GALP has anorexigenic effect directly on the hypothalamus (opposite of Galanin).  It also increases its responsiveness to the effects of leptin.  Apart from inhibition of feeding responses, GALP also leads to an increase in energy expenditure and fat oxidation in brown adipose tissue resulting in a hyperthermic effect.
  36. 36.  Corticotropin-releasing factor (CRF) and related peptides  CRF results in suppression of spontaneous feeding responses demonstrating its anorexigenic properties.  High serum cortisone has a negative feedback on CRF, leading to obesity.  The role of CRF as an anorexigenic hormone may involve the NPY, melanocortin and CART systems, acting in a downstream fashion.
  37. 37. Hypothalamic Lipid Metabolism and Energy Homeostasis  Within the central nervous system the metabolism of fatty acids is primarily for the purposes of membrane function and the central regulation of energy metabolism.  Fats do not serve as a major source of energy within the brain.  Fatty acids, specifically long-chain fatty acids via the formation of long-chain fatty acyl-CoAs, have very recently been shown to exert anorexigenic effects via the hypothalamus.
  38. 38.  Serotonin  Serotonin (5-HT) is a short-acting widespread neurotransmitter which acts on a number of receptor subtypes found at high density in the limbic system as well as in the hypothalamus.  5-HT stimulates noradrenaline release and modifies behaviour and mood.  5-HT shows the most consistent inhibition of food intake. Serotonin may directly influence the melanocortin pathway.
  39. 39.  Others  The dopaminergic system is also integral to reward- induced feeding behavior.  Other systems, including those mediated by serotonin, may also be able to modulate both reward circuitry and homeostatic mechanisms controlling feeding.  The noradrenergic system also plays a role in appetite regulation, with activation of α1- and β2- adrenergic receptors inhibiting food intake.
  40. 40.  Zinc:  Leptin levels decrease in response to zinc depletion and increases after zinc supplementation.  Importantly, the magnitude of leptin level changes were proportional to the changes of cellular zinc.  Zinc increases TNFa and IL-2 cytokine production.  Adequate zinc levels reduce appetite, possibly by increasing brain sensitivity to leptin.
  41. 41.  Probiotics:  Recently, a potential link between gut microbiota and obesity has emerged.  The study by Cani et al. [2011] evaluated the effect of prebiotics on plasma levels of gut hormones in healthy subjects.  After two weeks of prebiotic treatment, they observed increased gut microbiota fermentation, decreased appetite, and improved postprandial glucose responses.  Furthermore plasma levels of GLP-1 and PYY were increased in subjects following prebiotic treatment.
  42. 42.  Estrogen deficiency might result in a higher energy intake and increased body weight. Food intake varies across the menstrual cycle. Women tend to eat more in the luteal phase (the premenstrual period) compared with the follicular phase.  Testosterone (directly) seems to have little effect on food intake, although many people supplementing anabolic doses of testosterone (e.g. bodybuilders) do report increased appetite.  Including a balanced intake of omega-6:omega-3 fats can help with appetite regulation.  A high protein diet can reduce appetite.
  43. 43.  Fibre seem to help control appetite.  Refined carbohydrates, on the other hand, appear to increase appetite.  Dietary fat has mixed results; when combined with refined carbohydrate it seems to increase appetite while on its own or combined with protein, it typically decreases appetite.  Elderly people have less appetite than young people from not only decreased energy expenditure but also from mechanisms potentially involving sex–steroid balance as well as altered CNS signalling to and from peripheral organs.
  44. 44.  It’s now recognized that overfat individuals have lower blood concentrations of vitamins and minerals, especially Zinc, compared to leaner individuals.  This may lead to a greater appetite and changes in fat deposition.
  45. 45. Appetite regulation has so many factors!!!! Lets revise…..
  46. 46. Weight Control with Herbs and Oils
  47. 47. Phytochemicals and Weight Control  Phytochemicals are found in food items and herbal preparations where they could alter appetite beyond the effects expected by normal nutrient loads.  This added to the fact that they can exert far fewer side effects, may provide an alternative treatment or could be used to enhance the effect of prescription medications.
  48. 48. Phytochemicals that Decrease Body Weight through a Peripheral Mechanism  Korean Pine Nut Oil  Korean pine nut oil (P. koraiensis) contains triglycerides (TG) and more than 92% poly- and mono-unsaturated fatty acids (PUFAs and MUFAs) like pinolenic acid, linoleic acid and oleic acid.  Korean pine nut free fatty acids significantly increase the release of satiety hormones such as cholecystokinin (CCK) and GLP 1.  The appetite sensation "prospective food intake" and ―desire to eat‖ are also lowered, and these effects last up to 4 hours.
  49. 49.  Palm Oil + Oat Oil Fractions  Olibra is a fat emulsion formulated from palm oil (40%) and oat oil fractions (2.5%).  Its mechanism of action is similar to that of Korean pine nut oil, increasing and prolonging the release of peptide YY, CCK and GLP-1 which inhibit upper gut motility, generating an indirect satiety effect.  Double-blind, placebo-controlled reports indicate that Olibra administration to lean, overweight and obese individuals significantly reduced hunger and desire to eat with a consequent decrease of energy and macronutrient intake up to 36 hours post-consumption.
  50. 50.  Garcinia Cambogia (Gambooge)  G. cambogia is a tree indigenous to southeast Asia.  The pericarp rinds of the fruit have been used for centuries in regional cooking practices and are reported to make meals more filling and satisfying, without any reported harmful effects.  Commercially available Hydroxycitric acid (HCA) is mainly extracted from the dried and cured pericarp of the fruit of this species.  Enhanced satiety may account for the reported suppression of energy consumption
  51. 51.  Daily administration of a relatively low dose of HCA (900 mg/day) over two weeks, reduced EI and sustained satiety.  Some clinical studies with HCA have encountered mild adverse events such as headache, and upper respiratory tract and GI symptoms
  52. 52. Phytochemicals that Block Absorption Some phytochemicals act by blocking the breakdown and consequent absorption of dietary carbohydrates and/or lipids, by blocking the action of pancreatic lipase and amylase enzymes in the GIT.
  53. 53.  Tea Cathechins  Three kinds of tea: oolong, green, and black, are widely used as traditional healthy drinks all over the world.  Green and Oolong tea have been reported to have anti-obesity and hypo-lipidemic actions.  Black tea also contains many active ingredients; however some of these may not survive processing.
  54. 54.  Oolong Tea  Catechins in oolong tea are reported to prevent obesity by two main mechanisms: the inhibition of small-intestine micelle formation and the inhibition of α-glucosidase activity which would lead to a decrease in carbohydrate absorption.  In a double-blind, placebo-controlled study, twelve weeks daily administration of oolong tea (containing 690 mg of catechins) to normal and overweight males produced a significant reduction in body weight (1.5%), body mass index (BMI) (1.5%), waist circumference (2.0%), and body fat mass (3.7%), compared to the placebo group.
  55. 55.  Green Tea  The long term consumption of green tea and its extract (GTE, commercially available as pills, patches, gums, mints, extracts, and ice creams) have been associated with weight loss mainly through a thermogenic mechanism.  The main active ingredients in GTE – the catechins are responsible for many of the beneficial effects of green tea.  Catechins from GTE have been associated with an increase in sympathetic nervous system activity, thermogenesis and fat oxidation in humans.
  56. 56.  Green Coffee Bean  Green coffee bean extract (GCBE) contains 10% caffeine and 27% chlorogenic acid as the principal constituents.  However, the roasting process of coffee drastically reduces the level of chlorogenic acid and its related compounds.  The administration of instant coffee enriched with chlorogenic acid to humans induced a reduction in body fat and body mass at least in part due to a reduction in the absorption of glucose.
  57. 57.  The reduction of glucose absorption would ultimately lead to an increase in the consumption of fat reserves.  However, it is important to note that a major consequence of blocking digestion of carbohydrates in the proximal gut is colonic fermentation which leads to increased microbial production of gas in the bowel; this effect can limit its use.
  58. 58.  Citrus Aurantium  C. aurantium (Bitter Orange) contains alkaloids such as p-octopamine and synephrines which exert adrenergic agonist activity and are present in supplements designed to aid weight loss.  Synephrines could potentially increase energy expenditure and decrease food intake.  In addition, there is some evidence that C. aurantium synephrines, decrease gastric motility.  Overall, these studies reported a loss of 2.4–3.4 kg among participants using synephrines, while placebo groups lost 0.94–2.05 kg.
  59. 59. Phytochemicals that Decrease Body Weight through both Central and Peripheral Mechanisms  Caffeine  Caffeine is the most widely consumed behaviourally active substance in the world.  Almost all caffeine consumed comes from dietary sources (beverages and food), most of it from coffee and tea.  The central effects of caffeine at habitually consumed doses are due to its effects on the widely distributed adenosine receptors.  Caffeine also seems to exert thermogenic and lipolytic actions.
  60. 60.  Nicotine  Nicotine is an alkaloid naturally occurring in tobacco leaves and is their major addictive component.  Similar to caffeine, nicotine exerts its effect through central and metabolic actions.  Among several effects, nicotine reduces appetite and alters feeding patterns typically resulting in reduced body weight.  However, given the health and addiction issues surrounding smoking, this is not a viable, healthy weight reduction strategy!
  61. 61.  Khat  Catha edulis, commonly called Arabian tea or khat, is a flowering plant native to the Horn of Africa and the Arabian Peninsula.  Among communities from these areas, khat chewing has a long history as a social custom dating back thousands of years.  Khat contains a monoamine alkaloid called cathinone, an amphetamine-like stimulant, which is said to cause excitement, loss of appetite and euphoria.  Cathinone compounds affect appetite centrally, by acting in the hypothalamus.
  62. 62.  Apart from its central effect, cathinone enhances sympathomimetic activity leading to a delay in gastric emptying.  In healthy volunteers, khat chewing decreased hunger and increased fullness scores; this was associated to a prolonged gastric emptying which was significant when compared to lettuce chewing.
  63. 63.  Hoodia Gordonii  Hoodia gordonii is a leafless spiny succulent plant with medicinal properties. It grows naturally in South Africa and Namibia.  The flowers smell like rotten meat.  The centuries-old use of the meat of the plant to suppress appetite on long hunting trips in the Kalahari Desert that has stimulated the most interest.  In 1977, the South African Council for Scientific and Industrial Research (CSIR) isolated the ingredient in hoodia—now known as P57—which is responsible for its appetite-suppressant effect, and patented it in 1996.
  64. 64.  H. gordonii P57 is commercially available as pills, patches, and liquid.  H. gordonii’s actions are mainly appetite suppressant, anti-diabetic activity and delaying of gastric emptying.
  65. 65.  Caralluma Fimbriata (Slimaluma)  C. fimbriata is an edible succulent cactus that belongs to the family Asclepiadaceae.  Its key ingredients are pregnane glycosides, bitter principles, saponins and various other flavonoids.  The appetite suppressant and increased satiety action of C. fimbriata could be mainly attributed to the pregnane glycosides.  In the adipose tissue, pregnane glycosides reduces lipogenesis.
  66. 66.  In overweight humans, two months administration of C. fimbriata extracts lead to a reduction in appetite, body weight and waist circumference when compared to a control group.  Interestingly C. fimbriata selectively reduced the intake of refined sugars, sweets, cholesterol and saturated fats, without altering fruit, vegetable or fish intake.
  67. 67.  Coleus Forskohlii  Plectranthus barbatus, or more commonly known as Coleus forskohlii and Indian Coleus, is a tropical perennial plant related to the typical coleus species.  One of the main active compounds in C. forskohlii is forskolin, a diterpene that acts directly on adenylate cyclase.  Adenylate cyclase is an enzyme that activates cyclic adenosine monophosphate (cAMP), which promotes lipolysis, increases the body's basal metabolic rate, and increases utilisation of body fat.
  68. 68.  Administration of C. forskohlii extract to overweight women mitigated weight gain with no significant side effects.
  69. 69. Phytochemicals that Increase Appetite and Body Weight  Cannabis Sativa  Although the use of cannabis for medicinal purposes dates back at least four thousand years, understanding of the underlying pharmacology dates back only forty years.  Cannabinoids are known for their rewarding effects and for their ability to stimulate increases in food intake (e.g., the marijuana 'munchies').  Cannabis hyperphagia is largely attributable to actions at brain cannabinoid receptor.
  70. 70. Key Points  Appetite control is a complex process of peripheral GIT and central brain mechanisms.  Many gut hormones and pancreatic hormones play a role in appetite regulation.  Adipose tissue also a significant endocrine organ.  Many plants and herbs have long been used to modify appetite.  We are only now learning how they act on human physiology.
  71. 71. Q? Thank you