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/Ghsrf/f). We studied young (5–6 months) and old (15–17 months) aP2-Cre/Ghsrf/f mice and their age-matched controls. Interestingly, young aP2-Cre/Ghsrf/f 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/Ghsrf/f 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/Ghsrf/f mice exhibited improved insulin sensitivity and glucose tolerance. Importantly, old aP2-Cre/Ghsrf/f mice maintained higher core body temperature at 4◦C, 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/Ghsrf/f 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.
Original language | English (US) |
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Article number | 3002 |
Journal | International journal of molecular sciences |
Volume | 19 |
Issue number | 10 |
DOIs | |
State | Published - Oct 1 2018 |
Keywords
- Adipose tissues
- GHS-R
- Ghrelin
- Thermogenesis
- Tissue-specific knockdown mice
- UCP1
ASJC Scopus subject areas
- Catalysis
- Molecular Biology
- Spectroscopy
- Computer Science Applications
- Physical and Theoretical Chemistry
- Organic Chemistry
- Inorganic Chemistry