# Adherence to the Mediterranean Diet and Metabolic Gene Expression in Smokers: An Integrative Transcriptomic Approach

## TL;DR

This study shows that following a Mediterranean diet may help reduce smoking-related metabolic stress by altering gene expression in energy metabolism pathways.

## Contribution

The study provides novel insights into how Mediterranean diet adherence modulates gene expression in smokers.

## Key findings

- Smoking upregulates genes involved in glycolysis, lipid metabolism, and redox regulation.
- Mediterranean diet adherence is linked to reduced expression of genes related to glycolytic flux and lipid β-oxidation.
- The diet is associated with increased tricarboxylic acid cycle activity and reduced redox stress in smokers.

## Abstract

Background: Cigarette smoking disrupts cellular energy metabolism and remains a major global health problem. The Mediterranean diet, characterized by antioxidant and anti-inflammatory properties, has been implicated in the regulation of metabolic pathways. Objective: This study aimed to examine the association between adherence to the Mediterranean diet and the expression of energy metabolism-related genes in smokers aged 18–55 years. Methods: Smokers were classified according to their Mediterranean Diet Adherence Screener (MEDAS) scores into an adhering group (n = 24) and a non-adhering group (n = 24). Participant characteristics were recorded, blood samples were collected, and total RNA was isolated. Gene expression analysis was performed using a custom RT-qPCR array targeting energy metabolism-related genes. Pathway enrichment analysis was conducted using EnrichR Reactome 2024, and gene–metabolite relationships were explored using MetaboAnalyst 6.0 to support pathway-level interpretation. Results: Smoking was associated with coordinated upregulation of genes involved in glycolysis, glucose transport, lipid metabolism, amino acid metabolism, the pentose phosphate pathway, and redox regulation, consistent with a metabolically stressed state. In contrast, adherence to the Mediterranean diet was associated with lower expression of genes related to glycolytic flux, lipid β-oxidation, and amino acid turnover, alongside relatively higher engagement of tricarboxylic acid cycle-related pathways and reduced activation of redox-associated processes. Conclusions: Adherence to the Mediterranean diet was associated with differences in the expression of genes involved in cellular energy metabolism among smokers, suggesting a potential modulatory role of dietary patterns in smoking-related metabolic alterations.