Nutr Res Pract.  2026 Feb;20(1):3-15. 10.4162/nrp.2026.20.1.3.

Anti-obesity effects of Withania somnifera and Chrysanthemum zawadskii Herbich var. latilobum (Maxim.) Kitamura by regulating lipid metabolism and insulin signaling in 3T3-L1 adipocytes

• Park SH
• Ha Y
• Yoo E
• Jung J
• Park MR
• Kim S
• Kim JL
• Lee JW
• Lee M
• Kim OK

• KMID: 2577587
• DOI: http://doi.org/10.4162/nrp.2026.20.1.3

Abstract

BACKGROUND/OBJECTIVES
Obesity is a complex metabolic disorder characterized by excessive adipose tissue accumulation, dysregulated lipid metabolism, and insulin resistance, leading to an increased risk of metabolic disease. While Withania somnifera (AS) and Chrysanthemum zawadskii Herbich var. latilobum (Maxim.) Kitamura (C) have traditionally been used for their metabolic regulatory properties, their combined effects on adipogenesis, lipogenesis, lipolysis, and insulin signaling remain unexplored. Therefore, this study aimed to evaluate the anti-obesity effects of AS, C, and their optimal combination (ASC) in 3T3-L1 adipocytes by investigating their impact on lipid metabolism and glucose homeostasis.
MATERIALS/METHODS
Following adipogenic differentiation, 3T3-L1 adipocytes were treated with AS, C, and ASC at different concentrations.
RESULTS
AS, C, and ASC significantly inhibited adipogenesis by downregulating cyclic adenosine monophosphate (cAMP) response element-binding protein, peroxisome proliferator-activated receptor gamma, CCAAT/enhancer-binding proteins alpha and beta phosphorylation, thereby reducing lipid accumulation in adipocytes. They also suppressed lipogenesis by downregulating the expression of dephosphorylated acetyl-CoA carboxylase, fatty acid synthase, and lipoprotein lipase. In contrast, they markedly enhanced lipolysis, as evidenced by increased hormone-sensitive lipase and protein kinase A expression, along with elevated glycerol release and cAMP levels. Furthermore, AS, C, and ASC activated energy metabolism pathways, as indicated by the upregulation of AMP-activated protein kinase, uncoupling protein 1, and carnitine palmitoyltransferase 1A, suggesting a transition toward enhanced mitochondrial fatty acid oxidation. Notably, AS, C, and ASC significantly improved insulin signaling by restoring insulin receptor substrate 1, phosphoinositide 3-kinase, and Akt phosphorylation, while upregulating glucose transporter type 4 expression, indicating enhanced glucose uptake. Among all treatments, ASC showed relatively greater efficacy compared to AS or C alone, suggesting a potential additive effect.
CONCLUSION
These findings demonstrate that ASC effectively modulates multiple metabolic pathways in adipocytes, including adipogenesis, lipogenesis, lipolysis, energy metabolism, and insulin signaling, to exert its anti-obesity effects.

Keyword

Obesity; Withania; Chrysanthemum; lipolysis; lipogenesis