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The insulin resistant brain: impact on whole-body metabolism and body fat distribution – published online 16/02/2024

Heni graphical abstract

Martin Heni

Insulin exerts its actions not only on peripheral organs but also in the brain, where it impacts multiple brain functions. In this issue, Martin Heni ( provides a comprehensive overview of brain insulin’s role in human metabolism. After highlighting historical discoveries, the author describes how insulin passes into the human brain and summarises recent findings on brain insulin’s impact on whole-body metabolism, including effects on hepatic glucose production, insulin sensitivity and pancreatic insulin secretion. The effect of brain insulin on body weight and body fat distribution is also discussed, paying particular attention to brain insulin resistance and linking it to altered glucose metabolism, obesity and cognitive impairments. The author highlights that the work reviewed here provides the first indication of the potential involvement of brain insulin resistance in the pathogenesis of high-risk clusters of prediabetes and diabetes. Emerging treatment strategies for brain insulin resistance are also reviewed, highlighting their potential in addressing both metabolic and neurological disorders. The author concludes with future research perspectives and underscores the importance of further exploring brain insulin’s role in health and disease. The figures from this review are available as a downloadable slideset.

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