Long‐Term Dietary Restriction Has a Strong and Positive Effect on Both Hepatic and Peripheral Insulin Sensitivity, in an Age‐ and Diet‐Dependent Manner

Dietary restriction (DR) improves insulin sensitivity, however, it has not been tested in long-term interventions and with diet type as variable. Therefore, we exposed mice to either a low-fat (LF) or high-fat-sucrose (HFS) diet, either fed ad libitum (AL) or in a DR regimen from weaning till 2 years of age. Using an oral glucose tolerance test with [6,6-<sup>2</sup>H<sub>2</sub>]-labelled glucose, we found that DR markedly reduced plasma insulin concentrations and strongly elevated hepatic and peripheral insulin sensitivity when compared to AL cohorts. These effects of DR, however, appeared to depend on diet and age, with stable increases in hepatic and peripheral insulin sensitivities across all ages in the LF condition, while these became clearly less elevated in the HFS condition with advancing age.

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Publication Details

Journal
Aging Cell
Published
2025-11-10
DOI
https://doi.org/10.1111/acel.70285
Primary Topic
Genetics, Aging, and Longevity in Model Organisms
Type
article
Field-Weighted Citation Impact
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article

Long‐Term Dietary Restriction Has a Strong and Positive Effect on Both Hepatic and Peripheral Insulin Sensitivity, in an Age‐ and Diet‐Dependent Manner

Jean M. Fisher, Kaja Hribar, Marcel A. Vieira‐Lara, Jacky L. Snoep et al.
Aging Cell
Genetics, Aging, and Longevity in Model Organisms
article

Long‐Term Dietary Restriction Has a Strong and Positive Effect on Both Hepatic and Peripheral Insulin Sensitivity, in an Age‐ and Diet‐Dependent Manner

Jean M. Fisher, Kaja Hribar, Marcel A. Vieira‐Lara, Jacky L. Snoep, Dirk‐Jan Reijngoud, Aaffien C. Reijne, Barbara M. Bakker, Alžbeta Talarovičová, Gertjan van Dijk, David D. van Niekerk
article en

Abstract

Dietary restriction (DR) improves insulin sensitivity, however, it has not been tested in long-term interventions and with diet type as variable. Therefore, we exposed mice to either a low-fat (LF) or high-fat-sucrose (HFS) diet, either fed ad libitum (AL) or in a DR regimen from weaning till 2 years of age. Using an oral glucose tolerance test with [6,6-<sup>2</sup>H<sub>2</sub>]-labelled glucose, we found that DR markedly reduced plasma insulin concentrations and strongly elevated hepatic and peripheral insulin sensitivity when compared to AL cohorts. These effects of DR, however, appeared to depend on diet and age, with stable increases in hepatic and peripheral insulin sensitivities across all ages in the LF condition, while these became clearly less elevated in the HFS condition with advancing age.

Aging CellVol. 24(12)
University Medical Center Groningen (NL), University of Groningen (NL), Stellenbosch University (ZA), Delft University of Technology (NL)
National Research Foundation, Nederlandse Organisatie voor Wetenschappelijk Onderzoek, Ministerie van Economische Zaken en Klimaat
Openalex Percentile: Top 70%
Genetics, Aging, and Longevity in Model Organisms
DOIOpen Access PDFOpenAlex
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