Low molecular weight galactomannans-based standardized fenugreek seed extract ameliorates high-fat diet-induced obesity in mice via modulation of FASn, IL-6, leptin, and TRIP-Br2

Abstract

Background: Obesity is a complex, chronic metabolic disorder and its prevalence is increasing throughout most of the world. Low molecular weight galactomannans-based standardized fenugreek seed extract (LMWGAL-TF) has previously shown anti-diabetic and anti-hyperlipidemic potential. Aim: To evaluate the efficacy and mechanism of action of LMWGAL-TF in treating high fat diet (HFD)-induced obesity and hyperlipidemia in mice. Materials and methods: Male C57BL/6 mice were fed the HFD for 12 weeks and were co-administered with LMWGAL-TF (10, 30 and 100 mg kg⁻¹, p.o.). Variables measured were behavioral, biochemical, molecular and histopathological. In a separate in vitro experiment, copper-ascorbate (Cu-As)-induced mitochondrial oxidative damage was evaluated. Results: The HFD-induced increase (p < 0.001) in body weight, fat mass, lean mass, adipose tissue (brown, mesenteric, epididymal and retroperitoneal) and liver weight was significantly attenuated (p < 0.001) by LMWGAL-TF (30 and 100 mg kg⁻¹). The HFD-induced elevated levels of serum lipid, interleukins (ILs)-6 and leptin were significantly decreased (p < 0.001) by LMWGAL-TF (30 and 100 mg kg⁻¹). Elevated fatty acid synthase (FASn), IL-6, leptin and transcriptional regulator interacting with the PHD-bromodomain 2 (TRIP-Br2) mRNA expression in brown adipose tissue (BAT), liver, and epididymal fat were significantly down-regulated (p < 0.001) by LMWGAL-TF (30 and 100 mg kg⁻¹). Additionally, HFD-induced histological alterations in skeletal muscle, liver, white adipose tissue (WAT) and BAT were also reduced by LMWGAL-TF. Furthermore, the Cu-As-induced alteration in mitochondria oxidative stress (lipid peroxidation, protein carbonylation, glutathione, glutathione reductase, glutathione peroxidase, isocitrate dehydrogenase and α-ketoglutarate dehydrogenase) in skeletal muscle and BAT was significantly (p < 0.001) ameliorated by LMWGAL-TF (2, 4 and 6 mg mL⁻¹) treatment. It also reduced the Cu-As-induced mitochondrial swelling. Conclusion: LMWGAL-TF showed its beneficial effect in reducing HFD-induced obesity via down-regulation of FASn, IL-6, leptin, and TRIP-Br2 in mice.