Genetic deletion of soluble 5′-nucleotidase II reduces body weight gain and insulin resistance induced by a high-fat diet
(2019) Molecular Genetics and Metabolism — Vol. 126, n° 4, p. 377-387 (2019)
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Rider, Mark H. 
- Abstract
- We previously investigated whether inhibition of AMP-metabolizing enzymes could enhance AMP-activated protein kinase (AMPK) activation in skeletal muscle for the treatment of type 2 diabetes. Soluble 5′-nucleotidase II (NT5C2) hydrolyzes IMP and its inhibition could potentially lead to a rise in AMP to activate AMPK. In the present study, we investigated effects of NT5C2 deletion in mice fed a normal-chow diet (NCD) or a high-fat diet (HFD). On a NCD, NT5C2 deletion did not result in any striking metabolic phenotype. On a HFD however, NT5C2 knockout (NT5C2−/−) mice displayed reduced body/fat weight gain, improved glucose tolerance, reduced plasma insulin, triglyceride and uric acid levels compared with wild-type (WT) mice. There was a tendency towards smaller and fewer adipocytes in epididymal fat from NT5C2−/− mice compared to WT mice, consistent with a reduction in triglyceride content. Differences in fat mass under HFD could not be explained by changes in mRNA expression profiles of epididymal fat from WT versus NT5C2−/− mice. However, rates of lipolysis tended to increase in epididymal fat pads from NT5C2−/− versus WT mice, which might explain reduced fat mass. In incubated skeletal muscles, insulin-stimulated glucose uptake and associated signalling were enhanced in NT5C2−/− versus WT mice on HFD, which might contribute towards improved glycemic control. In summary, NT5C2 deletion in mice protects against HFD-induced weight gain, adiposity, insulin resistance and associated hyperglycemia.
- Affiliations
Citations
Johanns, M., Kviklyté, S., Chuang, S.-J., Corbeels, K., Jacobs, R., Herinckx, G., Vertommen, D., Schakman, O., Duparc, T., Cani, P., Bouzin, C., Andersén, H., Bohlooly-Y, M., Van der Schueren, B., Oscarsson, J., & Rider, M. H. (2019). Genetic deletion of soluble 5′-nucleotidase II reduces body weight gain and insulin resistance induced by a high-fat diet. Molecular Genetics and Metabolism, 126(4), 377-387. https://doi.org/10.1016/j.ymgme.2019.01.017 (Original work published 2019)