Hormonal
Enhancing insulin signaling specifically in adipose tissue improves obesity-related metabolic disorders by promoting healthy fat expansion and preventing ectopic fat accumulation, whereas enhancing insulin signaling in the liver exacerbates metabolic dysfunction.
Treating obesity-related metabolic issues requires targeting the right tissue. Simply boosting insulin systemically can be harmful, particularly to the liver. Future therapies must distinguish between adipose tissue (where boosting insulin helps store fat safely) and the liver (where boosting insulin worsens fat accumulation). Current clinical focus remains on lifestyle changes and existing drugs that improve sensitivity, but the research highlights the need for tissue-specific drugs.
While an enhancement of insulin signaling in the liver increases hepatic fat accumulation and exacerbates dyslipidemia, enhancement of insulin signaling in adipose tissue protects against obesity-related dysfunction of various organs by increasing the capacity for fat accumulation in the adipose tissue and inhibiting ectopic fat accumulation.
Why this rating
Evidence is derived from multiple tissue-specific knockout/transgenic mouse models (e.g., Adipoq-Cre, Alb-Cre) rather than human clinical trials.
Source
Tissue-specific activation of insulin signaling as a potential target for obesity-related metabolic disorders
Hideyuki Okuma et al. · Pharmacology & Therapeutics · 2024
DOI 10.1016/j.pharmthera.2024.108699
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