Hormonal
Obesity-associated insulin resistance is driven by the failure of adipose tissue expandability, which causes nutrient leakage and lipotoxicity in non-adipose organs, rather than by adipose mass alone.
Focus on improving adipose tissue health and capacity rather than just reducing total fat mass. Strategies that support safe lipid storage (e.g., through specific dietary patterns or medications that enhance adipose expandability) may be more effective for metabolic health than weight loss alone, which can sometimes exacerbate lipotoxicity if not managed correctly.
In states of overnutrition, the mere presence of excess adipose tissue mass alone is unlikely to be responsible for obesity-associated peripheral insulin resistance and metabolic disruption... the expansion of the adipose tissue and its storage capacity may be prefixed or limited... specific genetic profiles that were able to maintain the storage competence of the adipose tissue now fail to cope with the excessive demands.
Why this rating
Based on a thematic review of multiple rodent models and human genetic studies.
Source
Thematic review series: Adipocyte Biology. Adipose tissue function and plasticity orchestrate nutritional adaptation
Jaswinder K. Sethi et al. · Journal of Lipid Research · 2007
DOI 10.1194/jlr.r700005-jlr200
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