Benzyl isothiocyanate inhibits TNF -driven lipolysis via suppression of the ERK/PKA/HSL signaling pathway in 3T3-L1 adipocytes

Tumor necrosis factor alpha (TNF alpha), an inflammatory cytokine, induces lipolysis and increases circulating concentrations of free fatty acids. In addition, TNF alpha is the first adipokine produced by adipose tissue in obesity, contributing to obesity-associated metabolic disease. Given that benzyl isothiocyanate (BITC) is a well-known anti-inflammatory agent, we hypothesized that BITC can ameliorate TNF alpha-induced lipolysis and investigated the working mechanisms involved. We first challenged 3T3-L1 adipocytes with TNF alpha to induce lipolysis, which was confirmed by increased glycerol release, decreased protein expression of peroxisome proliferator-activated receptor gamma (PPAR gamma ) and perilipin 1 (PLIN1), and increased phosphorylation of ERK, protein kinase A (PKA), and hormone-sensitive lipase (HSL). However, inhibition of ERK or PKA significantly attenuated the lipolytic activity of TNF alpha. Meanwhile, pretreatment with BITC significantly ameliorated the lipolytic activity of TNF alpha; the TNF alpha induced phosphorylation of ERK, PKA, and HSL; the TNF alpha -induced ubiquitination of PPAR gamma ; the TNF alpha-induced decrease in PPAR gamma nuclear protein binding to PPAR response element; and the TNF alpha-induced decrease in PLIN1 protein expression. Our results indicate that BITC ameliorates TNF alpha-induced lipolysis by inhibiting the ERK/PKA/HSL signaling pathway, preventing PPAR gamma proteasomal degradation, and maintaining PLIN1 protein expression. (c) 2023 Elsevier Inc. All rights reserved.