ArticleScientific reports2026
Ramulus Mori (Sangzhi) alkaloids attenuate diet-induced obesity by modulating adipose tissue metabolic programs.
Article in Scientific reports, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Obesity is a chronic metabolic disorder characterized by excessive adipose accumulation and is closely associated with type 2 diabetes mellitus (T2DM), cardiovascular diseases, and metabolic dysfunction associated steatotic liver disease. Enhancing adipose metabolic activity, including thermogenic- and oxidative-related metabolic programs, has emerged as a promising strategy to counteract obesity and its related metabolic complications. Ramulus Mori (Sangzhi) alkaloids (SZ-A), a natural alkaloid complex derived from Morus alba L. (mulberry twig), are clinically approved for T2DM treatment and exhibit multiple metabolic regulatory properties; however, their anti-obesity mechanisms remain incompletely understood. In this study, male C57BL/6 mice were fed a high-fat diet (HFD) for 14 weeks to induce obesity and subsequently treated with SZ-A (200 or 600 mg/kg) for 6 weeks. SZ-A markedly attenuated HFD-induced body weight gain independent of food intake, improved glucose tolerance and insulin sensitivity, and alleviated dyslipidemia and hepatic steatosis. SZ-A also reduced the mass of multiple adipose depots and upregulated thermogenic regulators and beige adipocyte-associated markers in white adipose tissue (WAT). In brown adipose tissue (BAT), SZ-A partially restored HFD-impaired thermogenic features, accompanied by increased expression of uncoupling protein 1 (UCP1). In vitro, SZ-A directly promoted the expression of genes associated with adipocyte browning-related transcriptional features at the transcriptional level in differentiated 3T3-L1 adipocytes, supporting a cell-autonomous metabolic effect. Transcriptomic profiling of epididymal WAT (eWAT) revealed that SZ-A induced broad transcriptional remodeling, characterized by significant enrichment of fatty acid catabolism, β-oxidation, and lipid oxidative metabolism pathways, along with enrichment of brown adipocyte differentiation-related gene signatures. Collectively, these findings demonstrate that SZ-A exerts robust anti-obesity effects through coordinated regulation of adipose tissue metabolism, involving enhanced thermogenic-related molecular features in BAT and inguinal WAT (iWAT) and oxidative metabolic remodeling in visceral adipose tissue. Given its established clinical safety in T2DM, SZ-A represents a promising therapeutic candidate for adipose-based obesity and associated metabolic disorders.
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