Grape pomace extract, rich in phenolic compounds, attenuates obesity-induced nephropathy by modulating energy metabolism dysregulation and oxidative stress in mice fed a high-fat diet

Abstract

Obesity constitutes a significant risk factor for chronic kidney disease. High-fat diets (HFD) disrupt glucose and lipid metabolism and promote ectopic lipid deposition, leading to renal lipotoxicity and dysfunction. We recently reported that grape pomace extract (GPE), rich in phenolic compounds, has beneficial effects on obesity-related metabolic disorders. This study investigates whether GPE supplementation could revert or attenuate HFD-induced renal damage in mice. Male C57BL/6 mice were fed a standard diet (16% calories from fat) or HFD (60% calories from fat) with or without GPE (300 mg/kg body weight/day) for 16 weeks. Chronic consumption of HFD induced several obesity-related alterations such as increased visceral adipose tissue (VAT), insulin resistance, dyslipidemia along with altered markers of kidney function (higher levels of blood urea nitrogen, creatinine and kidney protein levels of Kim-1). This was associated with increased kidney lipid accumulation, glomerular and tubular injury and fibrosis. Supplementation with GPE mitigated all these adverse effects. GPE protected kidney function by modulating cell signals involved in energy metabolism (p-AMPK/p-ACC), inflammation (NLRP3/caspase-1/NF-κB/TNF-α pathway) and oxidative stress (oxidant species production and Nox4 downregulation). These findings support the use of grape-derived bioactive compounds, to counteract obesity-related renal injury.