Rutin attenuates tumor necrosis factor-α-induced inflammation and initiates fat browning in 3T3-L1 adipocytes: Potential therapeutic implications for anti-obesity therapy

Abstract

Obesity is linked with a pathological state of inflammation, leading to the development and aggravation of metabolic diseases. The adipose tissue secretes adipokines and cytokines like tumor necrosis factor alpha (TNF-α) which are implicated in adipocyte dysfunction, exacerbation of inflammation, and insulin resistance. Rutin, a flavonoid that occurs naturally in plants such as Fagopyrum tataricum and Aspalathus linearis, has been found to have a variety of bioactive properties. However, experimental evidence on the therapeutic effects of rutin against a broad spectrum of obesity-associated complications remains to be explored. Hence, the potential therapeutic effects of rutin against TNF-α-induced inflammation in 3T3-L1 adipocytes were examined. The experimental design involved exposing differentiated adipocytes to tumor necrosis factor (TNF)-α before treatment with rutin (10 μM), in comparison to positive controls CL 316,243 (1 μM), and isoproterenol (10 μM) for 6 hours. The findings demonstrated that exposing these adipocytes to TNF-α was linked with enhanced markers of inflammation, increased lipolysis, and impaired lipid metabolism. Interestingly, treatment with rutin was effective in decreasing pro-inflammatory cytokines like TNF-α and IL-6. Rutin reversed adipocyte dysfunction by restoring intracellular lipid accumulation and preventing TNF-α-induced lipolysis. Importantly, rutin also potentially induced browning of 3T3-L1 adipocytes, as seen with increased mRNA expression of PR domain containing 16 (Prdm16) and protein levels of peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC1α). These findings demonstrate the potential of rutin to block inflammation and reduce adipocyte dysfunction linked to obesity, in part by modulating molecular mechanisms involving adipogenesis, lipid metabolism, and fat browning. The current study is not without limitations, which include the use of only one cell line to test the efficacy of rutin, while in vivo or in human participants are required to confirm these findings. This could be essential to understand the potential therapeutic ramifications of rutin, including how they might influence the creation of novel anti-obesity treatments.