Metabolic Regulation and Insulin Sensitivity in Obesity

Metabolic regulation encompasses the complex interplay of hormonal, cellular and molecular pathways that maintain energy homeostasis. Insulin plays a central role in facilitating glucose uptake into skeletal muscle, suppressing hepatic glucose production and promoting lipid storage in adipocytes. In obesity, chronic caloric excess and adipose tissue expansion lead to dysregulated insulin signalling, often manifesting as insulin resistance. This state of diminished cellular response to insulin is fuelled by ectopic lipid accumulation, low-grade inflammation in adipose depots and altered secretion of adipokines. The resulting hyperinsulinaemia initially compensates for impaired signalling but eventually exacerbates metabolic dysfunction, driving the progression to type 2 diabetes and increasing cardiovascular risk. Recent advances have elucidated the mechanisms by which adipose tissue inflammation, fibrotic remodelling and cross-talk with immune cells impair insulin action, while nutrient-sensing pathways such as AMPK and mTOR integrate energy status with insulin sensitivity. Understanding these mechanisms has global significance, underpinning strategies for therapeutic intervention, lifestyle modification and the development of precision medicine approaches to curb the obesity epidemic and its metabolic sequelae.

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Metabolic Regulation and Insulin Sensitivity in Obesity publication trend

The graph below shows the total number of articles in metabolic regulation and insulin sensitivity in obesity across all publications each year (not limited to Nature Index journals).

Technical terms

Insulin resistance: A state in which cells fail to respond effectively to insulin, leading to impaired glucose uptake and elevated blood glucose levels.

Hyperinsulinaemia: An abnormally high concentration of insulin in the bloodstream, often a compensatory response to insulin resistance.

Adipokine: A bioactive peptide or protein secreted by adipose tissue that modulates metabolic and inflammatory processes.

Inflammasome: A multiprotein complex that activates inflammatory cytokines in response to cellular stress, contributing to insulin resistance in adipose tissue.

References

1. Plasma endotrophin levels correlate with insulin resistance in people with obesity. Journal of Clinical Investigation (2025).
2. Insulin: too much of a good thing is bad. BMC Medicine (2020).
3. Oleanolic Acid Improves Obesity-Related Inflammation and Insulin Resistance by Regulating Macrophages Activation. Frontiers in Pharmacology (2021).