Obesity is Gluttony Narrative

METABOLIC SYNDROME nature, medicine Abnormal hedonic response Abnormal satiety Abnormal homeostatic response Definition (IDF): Central obesity (usually BMI > 30 kg/m2), plus 2 of the following: - TGs > 150 mg/dL - HDL < 40-50 mg/dL ↑ blood pressure - hyperglycemia Food intake >> energy needs Abnormal nutrient sensing Abnormal central regulation of systemic metabolism: - Disrupted endocrine hormone axis (HPT) Dysregulated efferent autonomic nervous system Abnormal liver function: Systemic glucotoxicity Hepatic glucose output ↑ Glucose uptake 11 (& conversion into lipids) Fatty acid uptake 11 (& T conversion into TGs and Fatty liver disease Dysregulated afferent autonomic nervous system VLDL and their release into Heart disease the blood stream) Pre-diabetes, followed by overt diabetes Pancreatic islet mass T, followed by exhaustion Pancreatic hormones: Glucagon 1 Insulin T (but with resistance): Dietary nutrients 11 Abnormal gastrointestinal activity: - Dietary fats & sugar absorption T -Gut motility T - Alterations in gut microflora, Gut hormones: CCK Ghrelin PPY ECs ↑ GLP-1 1 Incretin action t: contributing to metabolic disease stimulates insulin release - inhibits glucagon release - increases insulin sensitivity - effects on gut motility GIP Systemic low-grade inflammation Abnormal visceral adipose tissue function: r- Glucose uptake Net result: (& conversion into lipids & I Anti-inflammatory & 11 pro-inflammatory cytokines stored as fat) Increased fat storage & fat tissue hypertrophy Lipid uptake 1↑ (& stored as fat) - Lipolysis ↑ (release of fatty acids into Adipose tissue hormones: Leptin T (but with resistance) satiety I energy expenditure immune dysregulation angiogenesis dysregulation subfertility bone dysfunction -Adiponectin gluconeogenesis ↑ glucose uptake t insulin sensitivity + body weight 1 Systemic lipotoxicity the blood stream) Abnormal muscle function: Glucose uptake Fatty acid uptake 11 Complications of Chronic Diabetes: - chronic kidney disease endothelial function - cardiovascular disease - peripheral nerve damage - eye disease & blindness - non-healing skin ulcers, usually leading to amputations - non-alcoholic fatty liver disease, which can lead to cirrhosis OVERVIEW