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aP2-Cre mediated ablation of GHS-R attenuates adiposity and improves insulin sensitivity during aging
Lin L.1,2; Lee J.H.1,3; Wang R.4; Wang R.5; Sheikh-Hamad D.6; Zang Q.S.7; Sun Y.1,8
2018-10-01
Source PublicationInternational Journal of Molecular Sciences
ISSN14220067 16616596
Volume19Issue:10
Abstract

Ghrelin 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
Indexed BySCI
Language英语
WOS Research AreaBiochemistry & Molecular Biology ; Chemistry
WOS SubjectBiochemistry & Molecular Biology ; Chemistry, Multidisciplinary
WOS IDWOS:000448951000157
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Document TypeJournal article
CollectionInstitute of Chinese Medical Sciences
Affiliation1.Children’s Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA
2.State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau 999078, China
3.College of Pharmacy, Gachon University, Incheon 21936, Korea
4.Institute of Critical Care Medicine, Heilongjiang Academy of Medical Science, Heilongjiang 150081, China
5.Key Laboratory of Exercise and Health Sciences of Ministry of Education, Shanghai University of Sport, Shanghai 200438, China
6.Department of Medicine, Baylor College of Medicine, Houston, TX 77030, USA
7.Department of Surgery, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
8.Department of Nutrition and Food Science, Texas A&M University, College Station, TX 77843, USA
First Author AffilicationInstitute of Chinese Medical Sciences
Recommended Citation
GB/T 7714
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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