Research
Hormonal
Ectopic lipid accumulation in the liver and skeletal muscle is a primary cause of insulin resistance, mediated by lipid metabolites like diacylglycerol (DAG) and ceramides which interfere with insulin signaling pathways.
Focus on reducing fat stored in your liver and muscles, not just overall weight. This can be achieved through modest weight loss, exercise, or specific medical treatments for conditions like NAFLD. Reducing intrahepatic triglycerides dramatically reverses insulin resistance.
GoodSupportsHIGH confidence
excess lipid content caused by obesity is a primary cause of insulin resistance and T2DM... ectopic lipid accumulation in peripheral tissues, especially in liver and skeletal muscle, can lead to more severe insulin resistance, even in the absence of visceral adiposity
Why this rating
Supported by extensive epidemiological data, animal models, and clinical observations of lipodystrophy.
Source
Insulin Resistance: From Mechanisms to Therapeutic Strategies
Shin-Hae Lee et al. · Diabetes & Metabolism Journal · 2021
DOI 10.4093/dmj.2021.0280
narrative_reviewCited 1,003×
Read the paper DOI resolved against Crossref · corpus check 2026-06-10
More from this paper
- Diacylglycerol (DAG) accumulation at the plasma membrane, specifically the sn-1,2 stereoisomer, activates Protein Kinase C (PKC) isoforms (PKCε in liver, PKCθ in muscle), which inhibits insulin signaling.Good
- Selective insulin resistance occurs in the liver where insulin fails to suppress hepatic glucose production (gluconeogenesis) but continues to stimulate lipogenesis (fat creation), leading to hyperglycemia and hepatic steatosis.Moderate
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