Succinate Enhances Lipolysis and Decreases Adipocytes Size in Both Subcutaneous and Visceral Adipose Tissue from High-Fat-Diet-Fed Obese Mice

Abstract

Obesity is a risk factor for many chronic diseases related to the overexpansion of adipose tissue during obesity, leading to metabolic dysfunction and ectopic lipids. Previous studies reported a close relationship between succinate and obesity and its co-morbidities, and studies have also reported on its anti-obesity potential. To confirm its efficacy in obesity interventions, we supplemented mice with obesity induced by a high-fat diet with succinate (1.5% m/v in drinking water) for 11 weeks without changing the diet. After succinate supplementation, the changes in body weight, adipose tissue deposition, glucose tolerance, energy expenditure and lipid metabolism were evaluated. It was found that succinate supplementation significantly decreased subcutaneous adipose tissue (HFD: 4239.3 ± 211.2 mg; HFD-SA: 3268.9 ± 265.7 mg. p < 0.05), triglyceride contents (decreased by 1.53 mmol/g and 0.39 mmol/g in eWAT and ingWAT, respectively, p < 0.05) and NEFA (decreased by 1.41 μmol/g and 1.31 μmol/g in eWAT and ingWAT, respectively, p < 0.05). The adipocytes’ sizes all significantly decreased in both subcutaneous and visceral adipose tissue (the proportion of adipocytes with diameters larger than 100 μm in eWAT and ingWAT decreased by 16.83% and 11.96%, respectively. p < 0.05). Succinate significantly enhanced lipolysis in adipose tissue (eWAT: Adrb3, Hsl and Plin1; ingWAT: Hsl and CPT1a; p < 0.05), whereas the expression of lipogenesis-related genes remained unchanged (p > 0.05). Succinate supplementation also enhanced the activity of BAT by stimulating the expression of Ucp1 and Cidea (p < 0.05). Our results reported that succinate has a potential beneficial effect on obesity pathogenesis but cannot efficiently decrease bodyweight.