Long-Term Dietary Restriction Has a Strong and Positive Effect on Both Hepatic and Peripheral Insulin Sensitivity, in an Age- and Diet-Dependent Manner
Joel C. Fisher (Stellenbosch University)
Aaffien C. Reijne (Rijksuniversiteit Groningen)
Kaja Hribar (University Medical Center Groningen)
Marcel A. Vieira-Lara (TU Delft - Applied Sciences)
Alzbeta Talarovicova (Rijksuniversiteit Groningen)
Dirk Jan Reijngoud (University Medical Center Groningen)
David D. van Niekerk (Stellenbosch University)
Jacky L. Snoep (Stellenbosch University)
Gertjan van Dijk (Rijksuniversiteit Groningen)
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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 [6,6-2H2]-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.