Hormonal
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.
In obesity, the failure of fat cells to store fat safely leads to fat spilling into the liver and muscles, causing insulin resistance. Restoring the ability of adipose tissue to sequester lipids (e.g., through weight loss or specific metabolic therapies) is critical for resolving systemic insulin resistance, not just treating the liver or muscle directly.
Obesity exerts deleterious effects on each of these adipocyte functions to cause insulin resistance... White adipocytes specialize in sequestering triglycerides away from the liver, muscle, and other tissues to limit toxicity... Obesity decreases the rates of white adipocyte glycerol 3-phosphate formation... and overall lipid metabolism enzymes are downregulated in obese, glucose-intolerant subjects.
Why this rating
The paper is a comprehensive review citing extensive literature, including knockout mouse models and human clinical observations, though it notes uncertainty on specific initiation mechanisms.
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
More from this paper
- 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.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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