Research
Hormonal
Obesity causes insulin resistance primarily through the expansion of adipose tissue mass, which acts as an endocrine organ secreting factors like TNF-alpha, FFAs, and leptin that impair insulin signaling in muscle and liver.
Focus on reducing central adiposity, as intra-abdominal fat is more metabolically harmful than peripheral fat. This involves addressing the endocrine function of fat tissue, not just weight loss, by managing factors like free fatty acid flux and inflammatory cytokines.
GoodSupportsHIGH confidence
the major basis for this link is the ability of obesity to engender insulin resistance... the past several years have witnessed an explosive increase in our understanding of what may now be referred to as the adipo-insulin axis.
Why this rating
The paper is a perspective/review summarizing decades of research, citing multiple animal models and human studies, but notes some mechanisms remain 'uncertain' or 'unproven'.
Source
Obesity and insulin resistance
Barbara B. Kahn et al. · Journal of Clinical Investigation · 2000
DOI 10.1172/jci10842
narrative_reviewCited 3,214×
Read the paper DOI resolved against Crossref · corpus check 2026-06-10
More from this paper
- Central (intra-abdominal) fat is significantly more strongly linked to insulin resistance and cardiovascular disease than peripheral (gluteal/subcutaneous) fat.Good
- Adipose tissue acts as an endocrine organ, secreting hormones like leptin and cytokines like TNF-alpha, which directly impair insulin signaling in peripheral tissues.Good
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