Figure 1.

The main actors of adaptive thermogenesis and their principle thermogenic mechanisms. Adipose tissues and muscles are the main actors of adaptive thermogenesis. White adipocytes are not thermogenic per se but can undergo browning to generate beige adipocytes. Bottom left panel: Brown and beige adipocytes use free fatty acids (FFA) to fuel the mitochondrial β-oxidation. β-oxidation generates reduced compounds (NADH, FADH₂) whose oxidation is used by the respiratory electron transport chain (complex I, II, III, IV) to pump protons (H⁺) into the intermembrane space. Thus, an electrochemical gradient is created and used by ATP synthase to produce ATP. UCP1 is present in the inner mitochondrial membrane and activated by FFA. UCP1 acts as a proton channel to dissipate the electrochemical gradient without producing ATP. Thus, to match the inefficient ATP production, the metabolism must increase and heat is produced. Bottom right panel: Myocytes express SERCA that is located in the sarcoplasmic reticulum (SR) membrane. SERCA transfers calcium (Ca²⁺) from the cytosol to SR lumen using ATP hydrolysis. The calcium gradient generated by SERCA is dissipated by ryanodine receptor (RyR1). SERCA transport activity can be inhibited by two peptides: phospholamban (PLP) or sarcolipin (SLN), but its ATPase activity remains. To match Ca²⁺ transport, ATP mitochondrial synthesis increases and heat is produced.