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

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dc.contributor.authorWilson, C.
dc.contributor.authorNikolic, A.
dc.contributor.authorKentish, S.
dc.contributor.authorShalini, S.
dc.contributor.authorHatzinikolas, G.
dc.contributor.authorPage, A.
dc.contributor.authorDorstyn, L.
dc.contributor.authorKumar, S.
dc.date.issued2016
dc.description.abstractGender-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.
dc.description.statementofresponsibilityCH Wilson, A Nikolic, SJ Kentish, S Shalini, G Hatzinikolas, AJ Page, L Dorstyn and S Kumar
dc.identifier.citationCell Death Discovery, 2016; 2(1):16009-1-16009-10
dc.identifier.doi10.1038/cddiscovery.2016.9
dc.identifier.issn2058-7716
dc.identifier.issn2058-7716
dc.identifier.orcidKentish, S. [0000-0002-5479-2643]
dc.identifier.orcidHatzinikolas, G. [0000-0001-5430-6396]
dc.identifier.orcidPage, A. [0000-0002-7086-5865]
dc.identifier.orcidKumar, S. [0000-0001-7126-9814]
dc.identifier.urihttp://hdl.handle.net/2440/103465
dc.language.isoen
dc.publisherSpringer Nature
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1021456
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1073771
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1091586
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1002863
dc.rights© 2016 Cell Death Differentiation Association. This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/ by/4.0/
dc.source.urihttps://doi.org/10.1038/cddiscovery.2016.9
dc.titleSex-specific alterations in glucose homeostasis and metabolic parameters during ageing of caspase-2-deficient mice
dc.typeJournal article
pubs.publication-statusPublished

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