# A Mediterranean Diet‐Based Food Mix Ameliorates Diabetes‐ and Obesity‐Associated Liver Alterations Through Mitochondrial and Metabolic Reprogramming

## TL;DR

A food mix based on the 1960s Mediterranean diet helps protect the liver from diabetes and obesity by improving mitochondrial function and metabolism.

## Contribution

The study reveals how a Mediterranean diet-based food mix protects the liver through metabolic and mitochondrial reprogramming in diabetic and obese mice.

## Key findings

- The MD cocktail reduced oxidative liver damage and improved mitochondrial function in diabetic and obese mice.
- The food mix preserved acylated carnitine derivatives and bile acid biosynthesis, supporting liver metabolism.
- It enhanced autophagy markers and reduced fibrosis, indicating hepatoprotective effects.

## Abstract

Metabolic syndrome (MetS)‐related diseases, such as type 2 diabetes (T2D) and obesity, are among the leading causes of liver damage, and their prevalence poses an increasing clinical challenge. The Mediterranean diet (MD) has shown promising effects in managing MetS, reducing mortality and morbidity. However, the precise biochemical and molecular mechanisms underlying the MD efficacy remain unclear. This study evaluated the effects of a lab‐designed balanced food mix, simulating the 1960s MD, on hepatic metabolic dysfunction in obese and diabetic db/db mice.

The MD cocktail, naturally rich in polyphenols, fructose, and monounsaturated fatty acids, prevented hyperlipidemia while not reversing diabetes and obesity. Gene expression, protein representation, and metabolomic analyses of liver tissues from MD‐fed db/db mice revealed reduced oxidative damage, preserved mitochondrial quality control, enhanced autophagy markers, and reduced fibrosis markers. The MD cocktail also enhanced liver mitochondrial mass and stimulated the OXPHOS system. It also preserved the hepatic pool of acylated carnitine derivatives and chenodeoxycholic acid, suggesting protective effects on mitochondrial β‐oxidation and bile acid biosynthesis, with an overall improvement of metabolite profiles.

The experimental MD cocktail exerted significant hepatoprotective effects, mitigating several diabetes‐ and obesity‐induced hepatic disturbances and beneficially affecting metabolic fluxes and tissue texture.

Metabolic syndrome (MetS)‐related conditions are key factors in liver damage. A Mediterranean lifestyle shows promise in managing MetS, though its mechanisms remain unclear. This study tested a lab‐designed food mix mimicking the 1960s Mediterranean Diet (MD) on obese and diabetic mice; it prevented hyperlipidemia and reduced oxidative liver damage, improved mitochondrial function, metabolomic profiles and autophagy, and decreasing fibrosis. Overall, the MD cocktail showed hepatoprotective effects.