Research
Hormonal
High-fat diets increase circulating lipopolysaccharide (LPS) levels ('metabolic endotoxemia'), which triggers systemic inflammation and insulin resistance via the TLR4 pathway.
High-fat meals can increase gut-derived toxins (LPS) in the blood, triggering inflammation that worsens insulin resistance. Reducing dietary fat, particularly saturated fats, may help lower this inflammatory burden.
GoodSupportsHIGH confidence
Cani et al. demonstrated that after 2–4 weeks of high-fat feeding the mice exhibited a significant increase in circulating LPS levels, which they called ‘metabolic endotoxemia’... LPS-infused animals developed the same phenotype as those on a high-fat diet, namely, obesity, insulin resistance, diabetes, hepatic steatosis and insulin resistance.
Why this rating
Strong mechanistic evidence in animals and correlational evidence in humans.
Source
Gut microbiota as a regulator of energy homeostasis and ectopic fat deposition: mechanisms and implications for metabolic disorders
Giovanni Musso et al. · Current Opinion in Lipidology · 2010
DOI 10.1097/mol.0b013e3283347ebb
narrative_reviewCited 186×
Read the paper DOI resolved against Crossref · corpus check 2026-06-10
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