title: Sex-specific alterations in glucose homeostasis and metabolic parameters during ageing of caspase-2-deficient mice.
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.
authors.affiliation: Centre for Cancer Biology, University of South Australia , Adelaide, SA, Australia.
authors.forename: C H
authors.initials: CH
authors.lastname: Wilson
authors.affiliation: Centre for Cancer Biology, University of South Australia , Adelaide, SA, Australia.
authors.forename: A
authors.initials: A
authors.lastname: Nikolic
authors.affiliation: Discipline of Medicine, University of Adelaide, Adelaide, SA, Australia; South Australian Health and Medical Research Institute, Adelaide, SA, Australia.
authors.forename: S J
authors.initials: SJ
authors.lastname: Kentish
authors.affiliation: Centre for Cancer Biology, University of South Australia , Adelaide, SA, Australia.
authors.forename: S
authors.initials: S
authors.lastname: Shalini
authors.affiliation: Discipline of Medicine, University of Adelaide , Adelaide, SA, Australia.
authors.forename: G
authors.initials: G
authors.lastname: Hatzinikolas
authors.affiliation: Discipline of Medicine, University of Adelaide, Adelaide, SA, Australia; South Australian Health and Medical Research Institute, Adelaide, SA, Australia.
authors.forename: A J
authors.initials: AJ
authors.lastname: Page
authors.affiliation: Centre for Cancer Biology, University of South Australia , Adelaide, SA, Australia.
authors.forename: L
authors.initials: L
authors.lastname: Dorstyn
authors.affiliation: Centre for Cancer Biology, University of South Australia , Adelaide, SA, Australia.
authors.forename: S
authors.initials: S
authors.lastname: Kumar