aP2-Cre mediated ablation of GHS-R attenuates adiposity and improves insulin sensitivity during aging

Ligen Lin, Jong Han Lee, Ruitao Wang, Ru Wang, David Sheikh-Hamad, Qun S. Zang, Yuxiang Sun

Research output: Contribution to journalArticle

1 Citation (Scopus)

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 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/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 languageEnglish (US)
Article number3002
JournalInternational Journal of Molecular Sciences
Volume19
Issue number10
DOIs
StatePublished - Oct 1 2018

Fingerprint

pituitary hormones
Ghrelin Receptor
insulin
Insulin
Hormones
Adiposity
Ablation
ablation
mice
Insulin Resistance
Aging of materials
sensitivity
Oils and fats
fats
food intake
Tissue
adipose tissues
Adipose Tissue
body weight
Fats

Keywords

  • Adipose tissues
  • Ghrelin
  • GHS-R
  • 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

Cite this

aP2-Cre mediated ablation of GHS-R attenuates adiposity and improves insulin sensitivity during aging. / Lin, Ligen; Lee, Jong Han; Wang, Ruitao; Wang, Ru; Sheikh-Hamad, David; Zang, Qun S.; Sun, Yuxiang.

In: International Journal of Molecular Sciences, Vol. 19, No. 10, 3002, 01.10.2018.

Research output: Contribution to journalArticle

Lin, Ligen ; Lee, Jong Han ; Wang, Ruitao ; Wang, Ru ; Sheikh-Hamad, David ; Zang, Qun S. ; Sun, Yuxiang. / aP2-Cre mediated ablation of GHS-R attenuates adiposity and improves insulin sensitivity during aging. In: International Journal of Molecular Sciences. 2018 ; Vol. 19, No. 10.
@article{d37cd12187b04dc4a59d2d6e4a6a12b4,
title = "aP2-Cre mediated ablation of GHS-R attenuates adiposity and improves insulin sensitivity during aging",
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.",
keywords = "Adipose tissues, Ghrelin, GHS-R, Thermogenesis, Tissue-specific knockdown mice, UCP1",
author = "Ligen Lin and Lee, {Jong Han} and Ruitao Wang and Ru Wang and David Sheikh-Hamad and Zang, {Qun S.} and Yuxiang Sun",
year = "2018",
month = "10",
day = "1",
doi = "10.3390/ijms19103002",
language = "English (US)",
volume = "19",
journal = "International Journal of Molecular Sciences",
issn = "1661-6596",
publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",
number = "10",

}

TY - JOUR

T1 - aP2-Cre mediated ablation of GHS-R attenuates adiposity and improves insulin sensitivity during aging

AU - Lin, Ligen

AU - Lee, Jong Han

AU - Wang, Ruitao

AU - Wang, Ru

AU - Sheikh-Hamad, David

AU - Zang, Qun S.

AU - Sun, Yuxiang

PY - 2018/10/1

Y1 - 2018/10/1

N2 - 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.

AB - 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.

KW - Adipose tissues

KW - Ghrelin

KW - GHS-R

KW - Thermogenesis

KW - Tissue-specific knockdown mice

KW - UCP1

UR - http://www.scopus.com/inward/record.url?scp=85054051541&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85054051541&partnerID=8YFLogxK

U2 - 10.3390/ijms19103002

DO - 10.3390/ijms19103002

M3 - Article

VL - 19

JO - International Journal of Molecular Sciences

JF - International Journal of Molecular Sciences

SN - 1661-6596

IS - 10

M1 - 3002

ER -