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In the name of God. Gut Hormones in the control of appetite. Ali Haghzaheri. Introduction. Obesity is one of the greatest threats to the health it is essential to understand the physiology of appetite control
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Gut Hormones in the control of appetite Ali Haghzaheri
Introduction • Obesity is one of the greatest threats to the health • it is essential to understand the physiology of appetite control • Obesity is a risk factor of type2 diabetes mellitus , CVD , certain forms of cancer • Obesity increases mortality • Weight loss can reduce the morbidity & mortality • Obesity is defined as BMI of 30 or more Exp Physiol 89.5 p 507 –“Gut hormones ih the control of appetite” , K.G Murphy & S.R. Bloom
Central mechanisms • Hypothalamus is key CNS region involved in appetite regulation • ARC play a crucial role in receiving & integrating signals • ARC involved are 2 types : POMC & NPY\POMC • POMC is precursor molecule that gives rise to the anorectic peptide alpha-MSH • AgRP increases food intake • NPY is a potent orexigenic agent & stimulates feeding Exp Physiol 89.5 pp 507-516 , K.G Murphy & S.R. Bloom
Adipostat factors • Leptin • Is expressed & secreted by adipocytes in white adipose tissue • Circulates in plasma at concentration proportional to fat mass • Provides the hypothalamus with information on the extent of body fat stores • Reduces food intake & body weight • Increases energy expenditure Exp Physiol 89.5 pp 507-516 , K.G Murphy & S.R. Bloom
Adipostat factors • Insulin • Is not released from adipocytes themselves, basal circulating levels correlated with body adiposity level • Reduces food intake & body weight Exp Physiol 89.5 pp 507-516 , K.G Murphy & S.R. Bloom
Gut Hormones • Leptin & insulin can not explain appetite changes • Endocrine & neural signals from gut are more responsible • Stomach distension is more important than content in the neural suppression of food intake • Nutrient content plays a larger role in small intestine , stimulating satiety • Gut hormones play a important physiological role in satiety Exp Physiol 89.5 pp 507-516 , K.G Murphy & S.R. Bloom
CCK • First gut hormone implicated in the control of appetite . • Presence of digestive products in the intestinal lumen stimulates the release of CCK from proximal small intestine • Has Anorectic effects Exp Physiol 89.5 pp 507-516 , K.G Murphy & S.R. Bloom
Ghrelin • Only peripherally active appetite-stimulating hormone so far discovered. • Potently stimulates food intake & GH secretion • Major source is stomach • Is orexigenic • Increases during fasting & fall rapidly after a meal Exp Physiol 89.5 pp 507-516 , K.G Murphy & S.R. Bloom
PP • It is found predominantly in the endocrine pancreas. • Its release is stimulated by food intake. • Postprandial plasma levels are proportional to caloric intake . • Though other factors, including gastric distension , vagal tone , blood glucose levels and GI hormones also influence its release. • PP inhibits pancreatic exocrine secretion & gallbladder contraction & GI motility. Exp Physiol 89.5 pp 507-516 , K.G Murphy & S.R. Bloom
PYY • PYY is produced by gut endocrine cells & is raleased into the circulation postprandially . • PYY increases fluid & electrolyte absorption from the ileum • & inhibits gut motility , meal-induced pancreatic & gastric secretion & gallbladder & gastric emptying. • It also acts as a vasocanstrictor. Exp Physiol 89.5 pp 507-516 , K.G Murphy & S.R. Bloom
GLP-1 • GLP-1 is produced by posttranslational processing of preproglucagon gene in the CNS & the intestine & colon. • GLP-1 is released into circulation in response to nutrient intake • It appear to function as satiety signals. • Physiological actions of GLP-1: stimulation of insulin release,suppression of gastric acid secretion & slowing gastric emtying. • GLP-1 receptors are found in the brainstem,ARC & PVN , in addition to various peripheral tissues. Exp Physiol 89.5 pp 507-516 , K.G Murphy & S.R. Bloom
Orexigenic neuropeptides • NPY • AgRP • MCH (melanin-concentrating hormones) • Galanin • Ghrelin • GHRH (Growth hormone Releasing hormone) • Orexin • Norepinephrine • Beta-Endorphin Molecular interventions ,volume2 ,issue8 , December 2002 ,p 497
Anorexigenic neuropeptides • Alpha-MSH • Corticopin-releasing hormone • CCK • Somatostatin • Thyrotropin-releasing hormone • Calcitonin-gene-related peptide • GLP-1 • GLP-2 • Serotonin • Oxytocin Molecular interventions ,volume2 ,issue8 , December 2002 ,p 497
References • Exp Physiol 89.5 (2004) pp 507-516 –“Gut hormones ih the control of appetite” , K.G Murphy & S.R. Bloom • Endocrinology,147 (6),March 2006,pp 2893-2901 : “Direct Stimulation of Ghrelin Secretion by Sympathetic Nerves” Thomas O. Mundinger ,… • Molecular interventions ,volume2 ,issue8 , December 2002 ,pp 494-498 : “Ghrelin & the regulation of food intake & Energy Balance” Hiroshi Hosoda ,…
The FASEB journal , vol 18 , pp 439-456 , March 2004 : “Ghrelin,appetite,and gastric motility: the emerging role of the stomach as an endocrine organ” AKIO INUI,…