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

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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

DOI 10.1530/joe-16-0449

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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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Additional file 5 of Effects of hyperinsulinemia on pancreatic cancer development and the immune microenvironment revealed through single-cell transcriptomics
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Additional file 1 of Effects of hyperinsulinemia on pancreatic cancer development and the immune microenvironment revealed through single-cell transcriptomics
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Additional file 3 of Effects of hyperinsulinemia on pancreatic cancer development and the immune microenvironment revealed through single-cell transcriptomics
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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)
ORCID: Templeman, Nicole M
Skovsø, Søs
Page, Melissa M
Lim, Gareth E
Johnson, James D
Venue: Journal of Endocrinology
Publisher: Bioscientifica
Published: 2017-03
Volume: 232
Issue: 3
Pages: R173-R183
ISSN: 0022-0795 (ISSN-L)
1479-6805
DOI: 10.1530/joe-16-0449
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: bronze
doi.org
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 › Endocrinology, Diabetes and Metabolism › 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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A causal role for hyperinsulinemia in obesity

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