Nobiletin ameliorates high-fat diet-induced vascular and renal changes by reducing inflammation with modulating AdipoR1 and TGF-β1 expression in rats.

Aims: We investigate the effect of nobiletin on vascular and renal alterations and possible mechanisms involved in high-fat diet (HFD)-fed rats.

Main Methods: Male Sprague-Dawley rats were fed a HFD with fructose 15% in drinking water for 16 weeks. HFD-fed rats were treated with nobiletin (20 or 40 mg/kg/day) or vehicle for the last 4 weeks.

Key Findings: HFD-fed rats treated with nobiletin was significantly reduced obesity, hypertension, dyslipidemia and hyperinsulinemia. Nobiletin improved vascular endothelial function, restored creatinine clearance, and reduced plasma urea and creatinine levels, as well as urinary protein excretion. Nobiletin markedly alleviated vascular medial cross-sectional area (CSA) and collagen deposition, glomerular extracellular matrix (ECM) accumulation, and renal fibrosis. Nobiletin significantly elevated plasma adiponectin levels, together with upregulated adiponectin receptor 1 (AdipoR1) and suppressed transforming growth factor-β1 (TGF-β1) expression in kidney. In addition, an increase of plasma tumor necrosis factor alpha (TNF-α) and interleukin 6 (IL-6) was significantly attenuated after nobiletin treatment.

Significance: Our results suggest that nobiletin attenuates HFD-induced vascular and renal alterations in rats, which is possibly related to the modulation of AdipoR1 and TGF-β1expression, and suppression of inflammation.