Category: signaling
Brown adipose tissue (BAT) burns chemical energy as heat via uncoupling protein 1 (UCP1) — distinct from white adipose tissue (WAT) energy storage. UCP1 sits in the mitochondrial inner membrane and dissipates the proton gradient, decoupling fuel oxidation from ATP synthesis → heat. Mechanism: cold exposure → sympathetic activation → norepinephrine → β3-adrenergic receptor on brown adipocyte → Gs → cAMP → PKA → HSL → lipolysis → free fatty acids → activate UCP1 (FFAs are required allosteric activators). Result: thermogenesis 100–300 W/kg BAT (vs. WAT near zero). BAT vs beige (brite) adipose: classical BAT is interscapular + supraclavicular (high UCP1, multilocular lipid droplets, dense mitochondria). Beige adipocytes appear in WAT depots after cold / exercise / β3 stimulation ("browning"). PRDM16 + PGC-1α are master transcriptional regulators. Human relevance: adult humans have functional BAT (FDG-PET-detectable) in supraclavicular + perirenal depots — activated by cold (~10× metabolic rate in BAT alone); inversely correlated with BMI, age, glucose intolerance. Therapeutic landscape: mirabegron — β3-AR agonist (FDA-approved for overactive bladder; off-label BAT activation trials show modest metabolic benefit); GLP-1 agonists + tirzepatide → indirect BAT effects via weight loss + central mechanisms; thyroid hormone (T3) → UCP1 expression; capsaicin / TRPV1 → cold-mimetic activation; cold exposure + exercise → BAT recruitment + WAT browning. Cross-links: [[adrenergic_receptor_signaling]] (β3-AR), [[catecholamine_synthesis]] (NE from sympathetic), [[hpt_axis]] (T3 enhancement), [[insulin_glucose_homeostasis]] (BAT improves glycemia).