Bioactive compounds from grape pomace and their role in obesity-related metabolic disorders

Abstract

Obesity is a major public health challenge characterized by chronic low-grade inflammation and associated with an increased risk of insulin resistance, type 2 diabetes, and metabolic dysfunction-associated steatotic liver disease (MASLD). Beyond adipose tissue dysfunction, growing evidence highlights the role of impaired intestinal barrier function in obesity-associated metabolic alterations. These disturbances promote metabolic endotoxemia, defined by the presence of bacterial-derived lipopolysaccharides (LPS) in circulation, thereby activating inflammatory pathways along the gut–liver axis. In this context, dietary bioactive compounds have emerged as promising nutritional interventions to counteract the harmful effects of Western-style diets. Grape pomace (GP), the main by-product of the winemaking industry, represents a sustainable and rich source of bioactive compounds, particularly polyphenols and dietary fiber. Polyphenols are recognized for their antioxidant and anti-inflammatory properties and have gained considerable attention because of their ability to modulate signaling pathways involved in inflammation and oxidative stress. The major polyphenols present in Malbec GP include flavanols (catechin, epicatechin, and procyanidins), flavonols (quercetin), stilbenes (resveratrol), and anthocyanins. Recent findings from our research group demonstrate that grape pomace extract preserves intestinal barrier integrity, reduces metabolic endotoxemia, and attenuates adiposity, inflammation, and metabolic dysfunction through modulation of the gut–liver axis. The molecular mechanisms underlying these effects and their implications for obesity and MASLD will also be discussed. Collectively, these findings support grape-derived bioactive compounds as promising nutritional tools for the prevention and management of obesity-related metabolic disorders and highlight grape pomace as a sustainable source of health-promoting ingredients within the framework of precision nutrition.

Obesity is a major public health challenge characterized by chronic low-grade inflammation and associated with an increased risk of insulin resistance, type 2 diabetes, and metabolic dysfunction-associated steatotic liver disease (MASLD). Beyond adipose tissue dysfunction, growing evidence highlights the role of impaired intestinal barrier function in obesity-associated metabolic alterations. These disturbances promote metabolic endotoxemia, defined by the presence of bacterial-derived lipopolysaccharides (LPS) in circulation, thereby activating inflammatory pathways along the gut–liver axis. In this context, dietary bioactive compounds have emerged as promising nutritional interventions to counteract the harmful effects of Western-style diets. Grape pomace (GP), the main by-product of the winemaking industry, represents a sustainable and rich source of bioactive compounds, particularly polyphenols and dietary fiber. Polyphenols are recognized for their antioxidant and anti-inflammatory properties and have gained considerable attention because of their ability to modulate signaling pathways involved in inflammation and oxidative stress. The major polyphenols present in Malbec GP include flavanols (catechin, epicatechin, and procyanidins), flavonols (quercetin), stilbenes (resveratrol), and anthocyanins. Recent findings from our research group demonstrate that grape pomace extract preserves intestinal barrier integrity, reduces metabolic endotoxemia, and attenuates adiposity, inflammation, and metabolic dysfunction through modulation of the gut–liver axis. The molecular mechanisms underlying these effects and their implications for obesity and MASLD will also be discussed. Collectively, these findings support grape-derived bioactive compounds as promising nutritional tools for the prevention and management of obesity-related metabolic disorders and highlight grape pomace as a sustainable source of health-promoting ingredients within the framework of precision nutrition.