Metabolic syndrome (MetS) is a globally prevalent comprehensive disease characterized by obesity, hypertension, hyperglycemia, and dyslipidemia (Fahed et al., 2022). With the increasing prevalence and younger age of onset, MetS has become a major global health issue. The concomitant presence of two or more significant factors in the pathogenesis of MetS substantially heightens susceptibility to chronic ailments, notably cardiovascular disease, and type 2 diabetes (Rong et al., 2024; Yasin et al., 2024).

While the incidence of MetS has risen over the past two decades, research on its pathogenesis has progressed more in-depth (Li et al., 2022). Lipid ectopic deposition, inflammation, and insulin resistance are recognized as the pathophysiological basis of MetS (Boren et al., 2013). Excessive energy intake surpassing energy expenditure is the most prevalent cause of ectopic lipid deposition, leading to the expansion of adipose tissue (Buitinga et al., 2023). In this context, excess lipids get infiltrate non-adipose organs such as the heart, liver, and kidneys, disrupting systemic energy homeostasis (Zhao et al., 2020). Commonly, adipocytes can be roughly divided into brown, white, and beige adipocytes according to their color (Park et al., 2014). In obesity, mitochondrial fragmentation in white adipocytes exacerbates metabolic dysfunction and suppresses energy expenditure. In contrast, brown and beige adipocytes have more mitochondria in the cytoplasm enriched with more uncoupling protein 1 (UCP1) and can produce more thermogenesis than white adipocytes (Saklayen, 2018). Although brown adipose tissue (BAT) is present and active in adults, its function declines in pathological states such as obesity, diabetes, and aging (Ruiz et al., 2018). Activating brown-like adipose tissue has emerged as a therapeutic target for obesity and diabetes, as it enhances energy expenditure and acts as a metabolic sink for excess lipids and glucose (Chand et al., 2024; Saito, 2013).

Traditional Chinese Medicine (TCM) is known for its minimal side effects, gradual efficacy, and minimal harm to the body, especially effective in the treatment of chronic diseases (Sang et al., 2018). Anemarrhenae rhizoma, the dried rhizome of the Anemarrhena asphodeloides Bunge, is widely applied in modern TCM (Zhang et al., 2014). Yunvjian is a classic TCM prescription that contains Anemarrhenae rhizoma, Luo et al. constructed a type 2 diabetes mellitus rat model and proved that Yunvjian had the function of improving glucose levels and insulin sensitivity (Luo et al., 2023). Timosaponin AIII (TAIII), a major saponin isolated from Anemarrhenae rhizoma, has shown potential in attenuating insulin resistance (Feng et al., 2021). Notably, TAIII was recently reported to ameliorate metabolic dysfunction-associated steatohepatitis (MASH) in calorie-restricted high-fat diet models, potentially through modulation of hepatic adenosine A1 receptor signaling (Zhu et al., 2024). Recent studies had further highlighted the therapeutic potential of TAIII-derived compounds in metabolic disorders. For instance, sarsasapogenin (ZGY), a gut metabolite of TAllI, ameliorates adipose tissue inflammation and insulin resistance in high-fat diet-fed mice by suppressing macrophage infiltration and inflammatory signaling pathways (Yu et al., 2021). Additionally, TAIII exerted anti-obesity and anti-diabetic effects by enhancing GLP-1 secretion and inhibiting adipogenesis (Park et al., 2024). However, limited articles discuss its pharmacological effects on an obese animal model. To address this gap, the present study investigated the lipid-lowering mechanisms of TAIII in leptin-deficient ob/ob mice, aiming to provide theoretical insights for the management of metabolic syndrome-related disorders.