#6 NS 160 Weight Control - Basics of Weight Control...

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Unformatted text preview: Basics of Weight Control Metabolism/ Life Physical activity Thermogene sis Growth Quantity of Food Caloric Content Digestibility of Food Energy Output Energy Input Energy Homeostasis must be tightly regulated to avoid an imbalance Anorexia Starvation Obesity BASICS OF WEIGHT CONTROL Short Term Control Hunger -> Eating -> Satiety Long-Term Control Maintenance of Body Weight and Adiposity Feeding Control Two Regulatory Circuits control Feeding Behavior Signals from both Systems are integrated in the Brain for a coordinated Response Gil-Campos et al., British J. of Nutrition, 2006 Short- and Long-term Energy Homeostasis Signals from the periphery are integrated by the Brain Stem and Hypothalamus A particularly important Nucleus within the Hypothalamus is called the Arcuate Nucleus (ARC) Feeding Control Images courtesy of Wikipedia Two sets of neurons in the Arcuate Nucleus, AgRP/NPY and POMC/CART are regulated by circulating hormones. Stimulating agouti-related protein (AgRP)/neuropeptide Y (NPY) neurons has orexigenic effects while proopiomelanocortin (POMC)/ cocaine- and amphetamine- regulated transcript (CART) neurons are anorectic Feeding Control Barsh and Schwartz, Nature Reviews Genetics, 2002 Neuropeptide Y (NPY) Agouti-related protein (AgRP) Orexins Reward System for palatable Food Feeding Control Central Orexigenic Signals 36 AA peptide with homologies to PYY (PP-fold family) binds to Y receptors (GPCRs) in the brain Expression in the ARC stimulated by fasting and suppressed by high-fat feeding Hypothalamic injection of NPY stimulates food intake and long-term infusion leads to obesity NPY KO mice have only subtle phenotype Neuropeptide Y FEEDING CONTROL Central Orexigenic Signals AgRP is a 132 AA peptide that acts as an inverse agonist (decreases G alpha binding and signaling upon binding) for MC4 receptors Co-expressed by NPY neurons in the ARC Hypothalamic injection of AgRP stimulates food intake and long-term infusion leads to obesity. Loss of MC4 receptors leads to obesity in humans and mice. AgRP is related to the Agouti coat color gene in mice. Agouti normally binds to MC1 receptors in the skin but a mutation in the Agouti (A y ) mice leads to ectopic expression leading to yellow coat color and obesity Agouti-related Peptide (AgRP) FEEDING CONTROL Central Orexigenic Signals Two homologous peptides A and B derived from the same 130 AA precursor expressed by dorsal and lateral hypothalamic neurons. Orexins delay the onset of normal satiety. Expression is increased in response to severe fasting and hypoglycemia. Orexins Disruption of Orexin or Orexin receptor genes causes Narcolepsy Source: Narcolepsy Center Stanford FEEDING CONTROL Central Orexigenic Signals FEEDING CONTROL Central Orexigenic Signals Reward System Rewarding nature of palatable food stimulates feeding....
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#6 NS 160 Weight Control - Basics of Weight Control...

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