Cited by 169Regulation of Appetite and ObesityAdipokines, Inflammation, and Metabolic DiseasesDiet, Metabolism, and Disease

A causal role for hyperinsulinemia in obesity

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Templeman, Nicole M, Skovsø, Søs, Page, Melissa M, Lim, Gareth E, Johnson, James D·2017·Journal of Endocrinology

Abstract

Insulin modulates the biochemical pathways controlling lipid uptake, lipolysis and lipogenesis at multiple levels. Elevated insulin levels are associated with obesity, and conversely, dietary and pharmacological manipulations that reduce insulin have occasionally been reported to cause weight loss. However, the causal role of insulin hypersecretion in the development of mammalian obesity remained controversial in the absence of direct loss-of-function experiments. Here, we discuss theoretical considerations around the causal role of excess insulin for obesity, as well as recent studies employing mice that are genetically incapable of the rapid and sustained hyperinsulinemia that normally accompanies a high-fat diet. We also discuss new evidence demonstrating that modest reductions in circulating insulin prevent weight gain, with sustained effects that can persist after insulin levels normalize. Importantly, evidence from long-term studies reveals that a modest reduction in circulating insulin is not associated with impaired glucose homeostasis, meaning that body weight and lipid homeostasis are actually more sensitive to small changes in circulating insulin than glucose homeostasis in these models. Collectively, the evidence from new studies on genetic loss-of-function models forces a re-evaluation of current paradigms related to obesity, insulin resistance and diabetes. The potential for translation of these findings to humans is briefly discussed.

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Authors
Templeman, N. M., Skovsø, S., Page, M. M., Lim, G. E., & Johnson, J. D.
Affiliations
University of British Columbia (CA)
Venue
Journal of Endocrinology
Published
2017-03
Volume
232
Issue
3
Pages
R173-R183
ISSN
  • 0022-0795 (ISSN-L)
  • 1479-6805
OpenAlex
W2570569124
Cited by
168
References
125
Citations by year
2026: 7 · 2025: 16 · 2024: 10 · 2023: 19 · 2022: 29 · 2021: 23 · 2020: 19 · 2019: 20 · 2018: 13 · 2017: 12
FWCI
2.12
Type
journal article
Language
en
Open access
Locations
  • Journal of Endocrinology (publishedVersion)
  • PubMed (publishedVersion)
  • Digital Access to Libraries (Université catholique de Louvain (UCL), l'Université de Namur (UNamur) and the Université Saint-Louis (USL-B)) (submittedVersion)
Funders
  • University of Miami
  • Canadian Diabetes Association
  • University of Alberta
  • University of British Columbia
  • Canadian Institutes of Health Research
Topics
  • Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
  • Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diet, Metabolism, and Disease
Keywords
hyperinsulinemia, obesity, insulin resistance, high-fat diet, weight gain, glucose homeostasis, lipid homeostasis, insulin reduction, diabetes mellitus, insulin signaling
MeSH terms
Animals, Humans, Hyperinsulinism, Insulin, Insulin Resistance, Obesity, Diet, High-Fat

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