Effect of dietary fat intake on metabolic endotoxemia: Mechanisms and clinical insights

Abstract

Background and aims

Dietary fat intake is recognized as a key influencer of metabolic endotoxemia; however, the exact nature of this relationship is not fully understood. This review aims to critically evaluate the effect of dietary fat intake on metabolic endotoxemia and elucidate the mechanisms linking dietary fats, metabolic endotoxemia, and chronic low-grade inflammation.

Methods

A comprehensive literature search from 2007 to 2025 was undertaken using PubMed, Google Scholar, ScienceDirect, and the Cochrane Library. The keywords used were “metabolic endotoxemia,” “dietary fat,” “fat intake,” “high-fat diet,” and “lipopolysaccharide.” Relevant human, animal, and mechanistic studies were reviewed, while non-English, duplicate, or irrelevant publications were excluded. A critical analysis of study methodologies and evidence quality was conducted.

Results

High-fat diet could lead to increased lipopolysaccharide (LPS) levels, subsequently triggering low-grade inflammation and metabolic dysfunction. Increased LPS transport through chylomicrons, disruption of the gut barrier, and changes in the microbiota that support LPS-producing bacteria are the primary drivers of this impact. Moreover, the type of dietary fats plays a significant role in metabolic endotoxemia; polyunsaturated fats may offer protective effects, whereas saturated fat facilitates LPS translocation. Different results have been obtained from the ketogenic diet, suggesting it may have anti-inflammatory effects in some circumstances while aggravating endotoxemia in others.

Conclusions

Dietary fat intake and metabolic endotoxemia have a complex relationship that is affected by gut microbiota, hepatic LPS clearance, total caloric intake, and overall metabolic health. Future studies should focus on long-term, well-controlled trials to better understand these relationships and guide dietary recommendations.