Taurine attenuates lipid accumulation via the eCB-CB1 axis: evidence from adipose metabolomics in HFD-fed mice and 3D adipocyte spheroids.

INTRODUCTION: Obesity, driven by adipose tissue dysfunction, is a major global health challenge and a key contributor to metabolic disorders. Although taurine shows anti-obesity potential, its precise mechanisms for attenuating adipocyte lipid accumulation remain unclear. METHODS: In this study, high-fat diet (HFD)-induced obese mice were treated orally with taurine (700 mg/kg/day) for 14 weeks. Systemic obesity-related parameters were evaluated, with a focus on epididymal white adipose tissue (eWAT). UPLC-MS-based metabolomics combined with multivariate analysis was employed to characterize metabolic alterations in eWAT. Additionally, 3T3-L1 adipocyte spheroids were treated with taurine (0-0.5 mM), either alone or in combination with the cannabinoid receptor type 1 (CB1) agonist CP55940 or antagonist AM6545, to assess its effects on lipid accumulation and underlying mechanisms. RESULTS: Focusing on adipose tissue, taurine treatment effectively countered HFD-induced metabolic disturbances, particularly by suppressing epididymal fat mass accumulation and ameliorating adipocyte hypertrophy. Metabolomic profiling of eWAT revealed that taurine treatment reversed 15 out of 35 metabolic alterations, including the reduction of three anandamide (AEA) precursors, implying that taurine may alter endocannabinoid (eCB) biosynthesis by limiting precursor availability. Moreover, taurine suppressed lipid accumulation by inhibiting CB1 signaling, a mechanism supported by downregulation of lipogenic genes (including Srebf1, Acaca, Cd36, and Pparg) and upregulation of lipolytic genes (including Pnpla2, Lipe, and Ppargc1a). CONCLUSION: Collectively, our findings demonstrate that taurine exerts its anti-obesity effects partially via modulation of eCB-CB1 signaling, coordinately inhibiting lipogenesis and promoting lipolysis, thereby highlighting its therapeutic potential for obesity management.