Metabolic Evaluation of a Novel Hydroxyfuranone Compound: Adiposity Reduction in Obese Mice by Increasing SIRT1 Gene Expression.

Abstract

Background: Obesity is one of the main health problems worldwide and is associated with type 2 diabetes mellitus. In this context, butenolides and sulfonamides are known for their anti-obesity effects.

Objectives: The present study aimed to synthesize a novel molecule containing the moieties hydroxybutenolide and sulfonamide [3-chloro-4-(p-chlorophenylsulfonylamino)-5- hydroxyfuran-2(5H)-one] (FS) and evaluate its metabolic effects in an obese mice model with metabolic syndrome.

Methods: 4 groups of mice were divided into standard diet (ST), standard diet with added hydroxybutenolide (ST+FS), high-fat diet (HF), and high-fat diet with added hydroxybutenolide (HF+FS). Over 30 days, FS was administered by gavage at a dose of 70 mg/kg/day. Body weight, food consumption, glycemic tests, total serum cholesterol, highdensity lipoprotein cholesterol, triacylglycerol, histological analyses, and gene expression by RT-PCR for the adipose tissue genes SIRT1, SIRT3, SIRT5, and NFKβ, were evaluated.

Results: A decrease in body weight was observed after FS administration (ST+FS: - 7.81±4.39 and HF+FS: -11.77±9.59), reducing glucose and fasting blood glucose in the treated group. Adipose tissue mass (ST+FS: 0.017 ±0.011; HF+FS: 0.062±0.017), white epididymal adipose tissue volume, triglycerides, as well as the adipocyte area, were lower for the HF+FS group. SIRT1 and SIRT3 expressions were higher in groups that received hydroxybutenolide.

Conclusion: Treatment with FS 3-chloro-4-(p-chlorophenylsulfonylamino)-5-hydroxyfuran- 2(5H)-one improved metabolic profile and increased the SIRT1 expression.