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Wilson CH, Nikolic A, Kentish SJ, et al. Sex-specific alterations in glucose homeostasis and metabolic parameters during ageing of caspase-2-deficient mice. Cell Death Discov. 2016;2:16009doi: 10.1038/cddiscovery.2016.9.
Wilson, C. H., Nikolic, A., Kentish, S. J., Shalini, S., Hatzinikolas, G., Page, A. J., Dorstyn, L., & Kumar, S. (2016). Sex-specific alterations in glucose homeostasis and metabolic parameters during ageing of caspase-2-deficient mice. Cell death discovery, 216009. https://doi.org/10.1038/cddiscovery.2016.9
Wilson, C H, et al. "Sex-specific alterations in glucose homeostasis and metabolic parameters during ageing of caspase-2-deficient mice." Cell death discovery vol. 2 (2016): 16009. doi: https://doi.org/10.1038/cddiscovery.2016.9
Wilson CH, Nikolic A, Kentish SJ, Shalini S, Hatzinikolas G, Page AJ, Dorstyn L, Kumar S. Sex-specific alterations in glucose homeostasis and metabolic parameters during ageing of caspase-2-deficient mice. Cell Death Discov. 2016 Feb 29;2:16009. doi: 10.1038/cddiscovery.2016.9. eCollection 2016. PMID: 27551503; PMCID: PMC4979492.
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Cell Death Discov. 2016 Feb 29;2:16009. doi: 10.1038/cddiscovery.2016.9. eCollection 2016.

Sex-specific alterations in glucose homeostasis and metabolic parameters during ageing of caspase-2-deficient mice.

Cell death discovery

C H Wilson, A Nikolic, S J Kentish, S Shalini, G Hatzinikolas, A J Page, L Dorstyn, S Kumar

Affiliations

  1. Centre for Cancer Biology, University of South Australia , Adelaide, SA, Australia.
  2. Discipline of Medicine, University of Adelaide, Adelaide, SA, Australia; South Australian Health and Medical Research Institute, Adelaide, SA, Australia.
  3. Discipline of Medicine, University of Adelaide , Adelaide, SA, Australia.

PMID: 27551503 PMCID: PMC4979492 DOI: 10.1038/cddiscovery.2016.9

Abstract

Gender-specific differences are commonly found in metabolic pathways and in response to nutritional manipulation. Previously, we identified a role for caspase-2 in age-related glucose homeostasis and lipid metabolism using male caspase-2-deficient (Casp2 (-/-) ) mice. Here we show that the resistance to age-induced glucose tolerance does not occur in female Casp2 (-/-) mice and it appears to be independent of insulin sensitivity in males. Using fasting (18 h) as a means to further investigate the role of caspase-2 in energy and lipid metabolism, we identified sex-specific differences in the fasting response and lipid mobilization. In aged (18-22 months) male Casp2 (-/-) mice, a significant decrease in fasting liver mass, but not total body weight, was observed while in females, total body weight, but not liver mass, was reduced when compared with wild-type (WT) animals. Fasting-induced lipolysis of adipose tissue was enhanced in male Casp2 (-/-) mice as indicated by a significant reduction in white adipocyte cell size, and increased serum-free fatty acids. In females, white adipocyte cell size was significantly smaller in both fed and fasted Casp2 (-/-) mice. No difference in fasting-induced hepatosteatosis was observed in the absence of caspase-2. Further analysis of white adipose tissue (WAT) indicated that female Casp2 (-/-) mice may have enhanced fatty acid recycling and metabolism with expression of genes involved in glyceroneogenesis and fatty acid oxidation increased. Loss of Casp2 also increased fasting-induced autophagy in both male and female liver and in female skeletal muscle. Our observations suggest that caspase-2 can regulate glucose homeostasis and lipid metabolism in a tissue and sex-specific manner.

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