褐色脂肪細胞由来のSAA3-CPT1A軸は食事誘発性熱産生を調節し、肥満を防御する

Diet-induced thermogenesis (DIT), a critical component of energy expenditure driven by brown adipose tissue (BAT), is essential for maintaining metabolic health; however, its precise molecular regulation remains poorly understood. We investigated whether Serum Amyloid A3 (SAA3), a factor secreted by brown adipocytes, regulates DIT and protects against diet-induced obesity. Using two distinct mouse models: mice with brown adipocyte-specific Saa3 deletion and mice with lentiviral-mediated Saa3 overexpression in BAT, we examined energy expenditure (EE), substrate utilization, and thermogenic responses under chow or short-term high-fat diet (HFD) feeding. SAA3 expression in BAT was acutely induced by refeeding. Loss of SAA3 severely diminished postprandial DIT and total EE, leading to accelerated weight gain on an HFD. Mechanistically, Saa3 deletion compromised UCP1 induction, chiefly by impairing ATGL-driven lipolysis and, critically, by inhibiting Carnitine Palmitoyltransferase 1A (CPT1A)-dependent fatty acid oxidation (FAO). Conversely, SAA3 overexpression robustly enhanced DIT, stimulated lipolysis and FAO, and promoted mitochondrial oxidative phosphorylation. Studies in primary brown adipocytes confirmed that SAA3 deficiency reduced CPT1A expression, palmitate-stimulated lipolysis, and mitochondrial respiration. Together, these findings identify the SAA3-CPT1A axis as a novel, BAT-intrinsic mechanism that couples nutrient sensing to UCP1 function via enhanced FAO. By promoting lipid utilization and postprandial energy dissipation, SAA3 optimizes postprandial thermogenesis and defends against obesity, highlighting conserved SAA signaling as a potential nutritional and therapeutic target in metabolic disease.