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aP2-Cre mediated ablation of GHS-R attenuates adiposity and improves insulin sensitivity during aging
Lin L.1; Lee J.H.1; Wang R.2; Wang R.3; Sheikh-Hamad D.1; Zang Q.S.5; Sun Y.1
2018-10-01
Source PublicationInternational Journal of Molecular Sciences
ISSN14220067 16616596
Volume19Issue:10
AbstractGhrelin via its receptor, the growth hormone secretagogue receptor (GHS-R), increases food intake and adiposity. The tissue-specific functions of GHS-R in peripheral tissues are mostly unknown. We previously reported that while GHS-R expression is very low in white and brown fat of young mice, expression increases during aging. To investigate whether GHS-R has cell-autonomous effects in adipose tissues, we generated aP2-Cre-mediated GHS-R knockdown mice (aP2-Cre/Ghsr). We studied young (5–6 months) and old (15–17 months) aP2-Cre/Ghsr mice and their age-matched controls. Interestingly, young aP2-Cre/Ghsr mice had normal body weight but reduced fat; old mice showed pronounced reductions of both body weight and body fat. Calorimetry analysis revealed that aP2-Cre/Ghsr mice had normal food intake and locomotor activity at both young and old age; but intriguingly, while energy expenditure was normal at young age, it was significantly increased at old age. Both young and old aP2-Cre/Ghsr mice exhibited improved insulin sensitivity and glucose tolerance. Importantly, old aP2-Cre/Ghsr mice maintained higher core body temperature at 4C, and showed higher expression of the thermogenic uncoupling protein 1 (UCP1) gene. The ex vivo studies further demonstrated that GHS-R deficient white adipocytes from old mice exhibit increased glucose uptake and lipolysis, promoting lipid mobilization. Despite the fact that the in vivo phenotypes of aP2-Cre/Ghsr mice may not be exclusively determined by GHS-R knockdown in adipose tissues, our data support that GHS-R has cell-autonomous effects in adipocytes. The anabolic effect of GHS-R in adipocytes is more pronounced in aging, which likely contributes to age-associated obesity and insulin resistance.
KeywordAdipose tissues Ghrelin GHS-R Thermogenesis Tissue-specific knockdown mice UCP1
DOI10.3390/ijms19103002
URLView the original
Language英語
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Document TypeJournal article
CollectionUniversity of Macau
Affiliation1.Baylor College of Medicine
2.Heilongjiang Academy of Medical Sciences
3.Shanghai University of Sport
4.Texas A and M University
5.UT Southwestern Medical School
6.Gachon University
7.Universidade de Macau
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Lin L.,Lee J.H.,Wang R.,et al. aP2-Cre mediated ablation of GHS-R attenuates adiposity and improves insulin sensitivity during aging[J]. International Journal of Molecular Sciences,2018,19(10).
APA Lin L..,Lee J.H..,Wang R..,Wang R..,Sheikh-Hamad D..,...&Sun Y..(2018).aP2-Cre mediated ablation of GHS-R attenuates adiposity and improves insulin sensitivity during aging.International Journal of Molecular Sciences,19(10).
MLA Lin L.,et al."aP2-Cre mediated ablation of GHS-R attenuates adiposity and improves insulin sensitivity during aging".International Journal of Molecular Sciences 19.10(2018).
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