# Biochemical, Molecular and Behavioral Changes Induced by High-fat and High-sugar Diets: A Systematic Review of Non-clinical Studies

## TL;DR

This review explores how high-fat and high-sugar diets affect the body and brain, leading to harmful biochemical, molecular, and behavioral changes.

## Contribution

The study systematically reviews non-clinical evidence linking high-fat/high-sugar diets to neural and physiological changes.

## Key findings

- High-fat and high-sugar diets induce physiological changes in the peripheral and central nervous systems.
- These diets are associated with changes in gut microbiota, glucose metabolism, and bile acid signaling.
- Adverse effects include neuronal and structural adaptations, suggesting a need for further research on prevention strategies.

## Abstract

Diets that promote excessive caloric intake, particularly those high in fat and/or sugar, can cause harmful changes in the human body, including the brain. Excess consumption of fat and sugar may impair neuronal function and have both short- and long-term adverse effects. This systematic review examined the influence of high-fat and/or high-sugar dietary patterns on biochemical, molecular, and behavioral changes (PROSPERO protocol number: CRD42024526471). A systematic search was conducted in PubMed, EMBASE, and Scopus, and twenty-eight articles were included for data extraction. The studies indicate that obesogenic and energy-dense dietary patterns induce physiological changes in both the peripheral and central nervous systems, leading to neuronal, functional, and structural adaptations accompanied by biochemical, molecular, and behavioral changes. These adaptations appear to be associated with coordinated changes in gut microbiota composition, glucose and insulin metabolism, and bile acid signaling pathways. These findings support further investigation into strategies for the prevention and treatment of diet-related cognitive impairment. However, additional non-clinical and clinical studies are needed to better elucidate the mechanisms linking energy-dense dietary patterns and excessive caloric intake to these neural changes.

The online version contains supplementary material available at 10.1007/s12035-026-05816-w.