Figure 8. Proposed mechanism by which the GPR120 agonist TUG‐891 activates BAT .

TUG‐891 selectively agonizes the Gαq‐coupled GPR120, which activates phospholipase C (PLC). Upon activation, PLC cleaves phospholipid phosphatidylinositol 4,5‐bisphosphate (PIP2) into diacyl glycerol (DAG) and inositol trisphosphate (IP3). IP3 triggers the opening of Ca²⁺ channels in the membrane of the endoplasmic reticulum, thereby increasing intracellular Ca²⁺ concentrations. Increased Ca²⁺ leads to depolarization of the mitochondria, and subsequently induction of mitochondrial fission which increases respiration. In addition, TUG‐891 directly activates UCP1, further stimulating uncoupled respiration and lipid combustion. As a consequence, the activated brown adipocytes take up fatty acids (FA) from triglyceride (TG)‐rich lipoproteins from the circulation, which eventually reduces fat mass.