Research
Hormonal
Adipose tissue inflammation and macrophage infiltration cause insulin resistance by increasing lipolysis, which floods the liver with fatty acids and glycerol, driving gluconeogenesis and hyperglycemia independently of hepatic insulin signaling.
In obesity, inflamed fat tissue releases excess fatty acids and glycerol, which force the liver to produce more glucose and fat. Reducing adipose inflammation and lipolysis (via weight loss) improves liver function.
StrongSupportsHIGH confidence
Subsequent macrophage infiltration into white adipose tissue (WAT) leads to increased lipolysis, which further increases hepatic triglyceride synthesis and hyperlipidemia... Macrophage-induced WAT lipolysis also stimulates hepatic gluconeogenesis.
Why this rating
Supported by human and animal studies linking macrophage infiltration to lipolysis and hepatic outcomes.
Source
The pathogenesis of insulin resistance: integrating signaling pathways and substrate flux
Varman T. Samuel et al. · Journal of Clinical Investigation · 2016
DOI 10.1172/jci77812
narrative_reviewCited 1,398×
Read the paper DOI resolved against Crossref · corpus check 2026-06-10
More from this paper
- Ectopic lipid accumulation (specifically diacylglycerol) in skeletal muscle and liver directly causes insulin resistance by activating specific protein kinase C (PKC) isoforms (PKCθ in muscle, PKCε in liver), which impair insulin receptor signaling.Strong
- Hepatic insulin resistance is characterized by a 'selective' defect where insulin fails to suppress gluconeogenesis but continues to stimulate de novo lipogenesis, driven by substrate flux (fatty acids and glucose) rather than insulin signaling alone.Strong
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