Withaferin A Protects Against High-Fat Diet–Induced Obesity Via Attenuation of Oxidative Stress, Inflammation, and Insulin Resistance
- Universiti Sains Malaysia, School of Chemical Sciences (Malaysia)
- Universiti Sains Malaysia, School of Materials & Mineral Resources Engineering (Malaysia)
- Universiti Sains Malaysia, Bioprocess Technology Division, School of Industrial Technology (Malaysia)
Withaferin A (WA), a bioactive constituent derived from Withania somnifera plant, has been shown to exhibit many qualifying properties in attenuating several metabolic diseases. The current investigation sought to elucidate the protective mechanisms of WA (1.25 mg/kg/day) on pre-existing obese mice mediated by high-fat diet (HFD) for 12 weeks. Following dietary administration of WA, significant metabolic improvements in hepatic insulin sensitivity, adipocytokines with enhanced glucose tolerance were observed. The hepatic oxidative functions of obese mice treated with WA were improved via augmented antioxidant enzyme activities. The levels of serum pro-inflammatory cytokines and hepatic mRNA expressions of toll-like receptor (TLR4), nuclear factor κB (NF-κB), tumor necrosis factor-α (TNF-α), chemokine (C-C motif) ligand-receptor, and cyclooxygenase 2 (COX2) in HFD-induced obese mice were reduced. Mechanistically, WA increased hepatic mRNA expression of peroxisome proliferator-activated receptors (PPARs), cluster of differentiation 36 (CD36), fatty acid synthase (FAS), carnitine palmitoyltransferase 1 (CPT1), glucokinase (GCK), phosphofructokinase (PFK), and phosphoenolpyruvate carboxykinase (PCK1) that were associated with enhanced lipid and glucose metabolism. Taken together, these results indicate that WA exhibits protective effects against HFD-induced obesity through attenuation of hepatic inflammation, oxidative stress, and insulin resistance in mice.
- OSTI ID:
- 22927757
- Journal Information:
- Applied Biochemistry and Biotechnology, Journal Name: Applied Biochemistry and Biotechnology Journal Issue: 1 Vol. 188; ISSN ABIBDL; ISSN 0273-2289
- Country of Publication:
- United States
- Language:
- English
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