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 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

Exp Physiol 89.5 (2004),p 508

The FASEB journal , vol 18 , p 442 , March 2004

Molecular interventions,volume2,issue8,December2002,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,…