Mitochondrial effects of a Mediterranean diet-based cocktail in the liver of diabetic/obese mice

Introduction: Mediterranean Diet (MD), known for its antiobesity, antioxidant, and anti-inflammatory properties, is considered a first-line dietary intervention to mitigate chronic and degenerative diseases such as type 2 diabetes (T2D) and related co-morbidities, including fatty liver. However, a detailed understanding of its protective effects at the molecular and subcellular levels,particularly under pathological conditions, remains incomplete.

Objectives: Aim of the study was to decipher liver mitochondrial effects of an home-designed food mix - an experimental cocktail for rodents simulating the Mediterranean food style of the 60s - tested in a mouse model of human T2D (db/db mice). Particular attention was paid on the mitochondrial compartment, given its central role in lipid and glucose metabolism and its susceptibility to oxidative stress, which can contribute to fibrosis and liver dysfunction.

Methods: Three levels of investigation were conducted: 1) design and production of the MD experimental cocktail; 2) bromatological and metabolite characterization of the cocktail compared to two commercially available diets: a standard (SD) and a western (WD) diet; 3) in vivo administration of the characterized diets to db/db mice, followed by ex-vivo analysis on liver mitochondrial pathways: biogenesis, dynamics and mitophagy in the context of tissue damage.

Results: The MD cocktail, rich in polyphenols, fructose, and monounsaturated fatty acids, exhibited high antioxidant capacity. Although it did not systemically counteract diabetes, it significantly reduced hepatic triglyceride accumulation, lipid peroxidation, and ROS production. Moreover, it affected mitochondrial mass, dynamics, and oxidative capacity, enhancing OXPHOS activity, while enriching the liver with antioxidants and metabolites, preserving key metabolic fluxes.

Conclusions: The obtained results provide novel insights into the subcellular targets of the MD and highlight its potential as a dietary strategy for improving liver health in T2D, paving the way for refined nutritional interventions in metabolic disease management.