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Obesity/Adipocyte Physiology and Pathophysiology - Coggle Diagram
Obesity/Adipocyte Physiology and Pathophysiology
Adipocytes
Functions of Functional Adipose Tissue
Energy (Storage/release, appetite, expenditure), Insulation, Reproduction, Skeleton, Mechanical (protection)
Deposits
Upper SAT is under skin, Visceral (intrabdominal fat)
Lipoproteins
LPL: Release FFA be deposited
HSL: Produces hormone structure sand releases FFA from TG
Regulation of Body Fat Stores
Increased fat -> Increased Leptin -> Decrease appetite and increase energy expenditure
Starvation: Decrease leptin -> Adaptive metabolic changes
Lipid accumulation
Major: Fatty acids from diet
Minor: De novo lipogenesis
LPL syntehsized and secreted by adipocytes reach capillary endothelial cells
ApoE brings HSPG to bring lipoprotien to LPL
apoC2 and A-V promote action of LPL on lipoprotien TG
FAs move throguh endothelium intoo adipocytes
Lipid Droplet
Structure similar to lipoprotein: Core of TG and covered by monolayer coat protein (perilipin)
Safe storage of Fatty acids
Perilipin
barrier role to maintain low rate of lipolysis in basal state
Factilitator role: Required for hormone stimulated lipolysis
Phosphorylation by PKA attracts HSL (hormone sensitive lipase) and lipase is brought to liquid droplet
HSL increases activity and translocates to lipid drop at perilipin-P (insulin inhibits lipolysis)
ABHD5
Dissociates from perilipin-P folllowing lipolytic stimulation, binds and activates ATGl which hydrolyzes triglycerides whcih leads to release of 3 FFA
Lipolysis
Insulin signaling and IR stimulates tyrosine Kinase activity
Phosphrylation of insulin receptor and substrate
PI3K associates with phosphorylated IRS and is activated
Activates PDE3B and leads to decreased cAMP
Leads to inability of fatty acid release
Adipose Tissue Measurement
Underwater Weighing (gold standard), Skinfold Calipers, DEXA
Distribution
Using MRI, MR Spectroscopy
Types of Weight Gain
High Proliferation and Differentiation Capacity
Low fat infiltration, Normal insulin secretion, HGP Suppression
Low Proliferationa nd Differentation Capacity
High fat infiltration, Decrease muscle glucose uptake, Decrease insulin mediated HGP suppression, Decrease insulin secretion, Increase Type 2 Diabetes Susceptibility
Increased Hypertrophy, Inflammation, Adipokines, Vascular injury, and CVD
Insulin Resistance
Metabolic (cardiovascular dysfunction), associated with objesity, Insulin resistance causing impaired glucose tolerance leading to Type 2 DM, Atherogenic lipid profile, Hypertension,
Insulin resistant obesity has adipocyte hypertrophy, macrophage infiltration, inflammation
Has a high fasting insulin
Lipotoxicity
Ectopic build up of FA metabolites in muslce and liver, and not safely stored
Activation of Serineand theronine kinases in muscle and liver by FA metabolites to phosphorylate IRS
Inhibits insulin stimulated tyrosine phosphorylation of IRS -> Blocks insulin action
TNF alpha
Increase production by adipocytes in obesity/T2DM
Activates serine/theronine kinases that phosphorylates IRS
Decrease ability of the insulin receptor to tyrosine phosphorylate IRS
Increase adipocyte lipolysis independent of effects
Interleukin (IL-6)
Increase production and secretion by adipocytes
Decreased insulin action, suppression of cytokine signalling
Increase adipocyte lipolysis independently of effects
Adiponectin
Decrease production and secretion by adipocytes in obesity/Type2DM
Increase insulin action at liver and muscle by stimulating FA oxidation (reducing intracellualr lipids)