Obesity, a global health concern characterized by excessive fat accumulation, necessitates the discovery of anti-obesity compounds. Rottlerin, known for its anti-cancer effects as a mitochondrial uncoupler, has been a subject of interest. However, its impact on reducing intracellular lipid accumulation remains a gap in our understanding. This study aimed to fill this gap by dissecting the mechanism of rottlerin in 3T3-L1 adipocytes. We treated differentiated 3T3-L1 cells with 0-20 mM of rottlerin for 48 hours to assess its capability to induce lipid accumulation. Notably, we observed no cytotoxicity associated with the treatment of rottlerin up to 20 mM, indicating its safety at these concentrations. Lipid accumulation, measured by oil Red O, was downregulated dose-independently by rottlerin. We also found that key lipogenic enzymes, including SCD1 and DGAT1, were decreased. The transcription factor of lipogenic genes, SREBP1, was reduced by approximately 80% with rottlerin. LRP6, a crucial link between de novo lipogenesis mechanism reactions and Wnt signaling, was also degraded by around 70%. Interestingly, the downstream regulation of LRP6, b-catenin, and TCFL2 was diminished by rottlerin. Our data indicate that rottlerin alleviates adipocyte lipid accumulation by suppressing the LRP6/β-catenin/SREBP1c pathway. These findings underscore the potential of rottlerin as a safe nutraceutical for combating obesity.

Obesity is the cause of many diseases, and its severity continues to increase. Promoting non-shivering thermogenesis is attracting attention as a new treatment strategy for obesity. This study summarized the studies that evaluated the effect of Panax ginseng on promoting non-shivering thermogenesis in animal models. A total of 7 studies were included according to the selection criteria, of which five were judged to have a high risk of bias. Indicators of UCP1 mRNA, UCP1 protein, and PGC- 1a were used in the meta-analysis, and the certainty of evidence progressed for each indicator, with UCP1 protein showing the highest certainty of evidence. Meta-analysis was conducted on 5 works of literature with standard indicators. As a result of meta-analysis, UCP1 protein level and PGC-1a mRNA level were significantly increased statistically. In addition, the protein levels of PRDM16 and TFAM increased in several studies (not a meta-analysis). These findings suggest that Panax ginseng could be a potential therapeutic agent for obesity. However, further research is needed to understand its mechanisms and possible side effects fully. Thus, it is concluded that Panax ginseng in animal models can promote non-shivering thermogenesis and improve mitochondria function in animal models, opening up new avenues for research and potential clinical applications.

Obesity, characterized by excessive fat accumulation, poses global health risks, including metabolic disorders like type 2 diabetes and cardiovascular diseases, with its prevalence steadily rising. This study proposes that rottlerin induces anti-obesity effects by enhancing non-shivering thermogenesis in beige adipocytes D16 via LRP6 inhibition. As a result, treatment of D16 cells with rottlerin up to 5 mM showed no cytotoxicity. Rottlerin significantly increased the expression of proteins involved in substrate oxidation, such as UCP1 and PGC1a, while decreasing the expression of C/EBPb associated with adipogenesis. Additionally, PRDM16, regulating brown adipocyte development, exhibited increased expression. The phosphorylation of LRP6, an indicator for Wnt signaling and nutrient-sensing pathway, is decreased by rottlerin. In conclusion, the study highlights the reduced phosphorylation of LRP6 as a pivotal mechanism by which rottlerin promotes the “beigeing” of D16 adipocytes, subsequently inducing non-shivering thermogenesis. This underscores rottlerin’s potential as a natural bioactive compound with anti-obesity effects.