Metabolic Evaluation of a Novel Hydroxyfuranone Compound: Adiposity Reduction in Obese Mice by Increasing SIRT1 Gene
Daniel Silva Moraes1, Suely Rodrigues Pereira2, Tulio Duque Esteves3
1Health Science Laboratory, Postgraduate Program in Health Science, Universidade Estadual de Montes Claros (Unimontes), Montes Claros, Minas Gerais, Brazil.
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.
