Research
Hormonal
Downregulation of specific adipokines (e.g., adiponectin, Neuregulin 4) and batokines (e.g., 12-HEPE, 12,13-diHOME) in obesity contributes to systemic insulin resistance by failing to suppress hepatic lipogenesis and promote peripheral glucose uptake.
Maintaining healthy adipose tissue function involves not just storage capacity but also the secretion of beneficial hormones. Obesity suppresses these protective factors (like Nrg4 and adiponectin), worsening insulin resistance. Weight loss and exercise can help restore these beneficial secretions.
GoodSupportsHIGH confidence
Obesity can downregulate both protein and lipid factors secreted specifically by adipocytes that normally act to maintain normal systemic insulin sensitivity in the liver and skeletal muscle... thereby contributing to systemic glucose intolerance and insulin resistance.
Why this rating
Supported by knockout mouse studies (Nrg4 KO, 12-LOX KO) and human correlation data.
Source
Mechanisms of insulin resistance related to white, beige, and brown adipocytes
Michael Czech · Molecular Metabolism · 2020
DOI 10.1016/j.molmet.2019.12.014
narrative_reviewCited 248×
Read the paper DOI resolved against Crossref · corpus check 2026-06-10
More from this paper
- Obesity-induced dysfunction of white adipose tissue (WAT) lipid sequestration capacity drives systemic insulin resistance by allowing toxic lipid accumulation in the liver and skeletal muscle, thereby increasing hepatic glucose output and impairing peripheral glucose disposal.Good
- Brown and beige adipose tissue (BAT) enhances systemic glucose tolerance and insulin sensitivity through increased energy expenditure, glucose uptake, and secretion of beneficial factors (batokines), although their role in human insulin resistance resolution is complex and context-dependent.Moderate
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