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Obesity Pathogenesis

Obesity: Pathogenesis Authors: En Chi Chen, Run Xuan (Karen) Zeng Reviewers: Gurreet Bhandal, Raafi Ali, Mizuki Lopez Energy homeostasis dysregulation (Peptide hormones regulating hunger/satiety that influence the hypothalamic control of eating behaviours) Luiza Radu, Dr. Sam Fineblit* * MD at time of publication Endocrine dysregulation Neurological (↓ caloric reserve activates the neurological system) Adiposity-related Hypothalamus (hemostatic area) ↑ Production of ghrelin (peptide hormone) ↑ Activation of agouti-related protein (A Neuropeptide Y (NPY) neuron clusters in the hypothalamus via vagus nerve ↑ Appetite Mesolimbic area (hedonic area) Reward Driven Eating (meso-limbic region of brain) ↑ Food consumption ↑ Dopamine & endogenous opioid signals ↑ Pleasure & desire to consume more food Prefrontal cortex (executive functioning) ↓ Glucagon-like peptide-1 (GLP-1) & pancreatic peptide YY (PYY) secretion post- meal ↓ Stimulation of Proopiomelanocortin (POMC) neuron clusters in hypothalamus ↓ Beta-melanocyte stimulating hormone (MSH) (endogenous peptide) production Defect in leptin receptor gene ↓ Circulating soluble leptin receptors (SLR) ↑ Serum leptin levels Leptin resistance Inactive leptin gene ↓ Adipocyte leptin production & secretion ↓ Leptin transport across blood brain barrier ↓ Hypothalamus suppression of hunger ↓ Satiety sensation ↑ Caloric intake & weight gain ↑ Dietary carbohydrate intake ↑ Insulin production & secretion ↓ Cellular response to insulin ↑ Insulin resistance ↑ Insulin production & secretion to compensate for insulin resistance Impaired glycemic control Metabolic syndrome, type 2 diabetes mellitus and cardiovascular disease ** Metabolic adaptation to reduced-caloric intake efforts ↑ Body energy conservation ↓ Baseline energy expenditure ↓ Resting metabolic rate (the amount of energy body requires to function while at rest) ↓ Ability to lose weight & fat mass ↑ Hunger ↑ Caloric intake & weight gain Obesity (A combination of metrics including ↑ BMI, ↑ weight circumference, ↑ waist-to-hip ratio, skinfold thickness, and other standardized measures varied by equipment available at various institutions resulting in a negative impact on the health of the individual) **See slide on Pathogenesis of Type II Diabetes Mellitus Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published Aug 13, 2024 on www.thecalgaryguide.com