Effects of diallyl disulfide administration on insulin resistance in high-fat diet-fed mice

Objectives: Diallyl disulfide (DADS) is a natural organosulfur compound found in garlic and related plants with various pharmacologic effects. However, whether DADS improves obesity-induced insulin resistance (IR) and its underlying mechanisms remain unclear. The aim of this study was to investigate the effects of DADS on systemic IR in high-fat diet-induced obese mice. Methods: To induce obesity, 8-wk-old male C57BL/6J mice were fed a high-fat diet (60% fat/kcal). The mice were assigned to three weight-matched groups: control (CON, n = 8), low-dose DADS (DADS-L, n = 8), and high-dose DADS (DADS-H, n = 9). The treated mice were orally administered DADS (25 or 100 mg/kg) 5 d/wk for 8 wk. At 15 wk of age, an intraperitoneal glucose tolerance test (GTT) and insulin tolerance test (ITT) were performed. Twenty-four hours after the final administration of DADS, epididymal fat and the liver were sam-pled after a 5-h fast. Results: DADS administration significantly attenuated body and fat weight gains during the experimental period. Additionally, systemic IR, as evaluated by ITT, was significantly improved by DADS administration in a dose-dependent manner. High-dose DADS administration significantly decreased liver triacylglycerol lev-els. Moreover, high-dose DADS administration decreased the c-Jun N-terminal kinase (JNK) phosphorylation and significantly increased heat shock protein 72 expression in the liver. Conclusions: The results of this study suggested that DADS administration alleviated systemic IR in obese mice. This may be associated with decreased hepatic fat accumulation and a heat shock protein 72-mediated decrease in JNK activity in the liver. (c) 2023 Elsevier Inc. All rights reserved.