| Status | 已發表Published |
| AP2-Cre mediated ablation of GHS-R reduces adiposity and improves insulin sensitivity | |
Lin, L.  ; Saito, K.; Lee, J.; Pradhan, G.; Xu, Y.; Sun, Y.
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| 2015-05-31 | |
| Source Publication | Cold Spring Harbor-Asia Conference
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| Abstract | Ghrelin, via its receptor growth hormone secretagogue receptor (GHS-R), increases food intake and fat deposition. However, the tissue-specific functions, particularly in peripheral tissues are unknown. GHS-R expression in white and brown fat increases during aging. We previously reported global GHS-R deletion leads to leanness and improved insulin sensitivity in aging due to elevated thermogenesis. To investigate whether GHS-R has cell-autonomous effects in adipose tissues, we generated aP2-Cre mediated GHS-R knockout mice (aP2-Cre;Ghsrf/f). Our validation showed that GHS-R coding DNA was completely deleted in both white and brown fat, but not in muscle, pancreas and liver. aP2-Cre is known to have ectopic expression in hypothalamus and macrophages. Partial GHS-R gene deletion was detected in hypothalamus and macrophage-containing tissues. We characterized chow–fed young and aged aP2-Cre;Ghsrf/f mice and their controls. aP2-Cre;Ghsrf/f mice had normal body weight with reduced body fat at young age; interestingly, they exhibited reduced body weight and body fat at older age. Calorimetry analysis further revealed that aP2-Cre;Ghsrf/f mice had normal food intake and locomotor activity; had normal energy expenditure at young age, but increased energy expenditure at older age. Importantly, aP2-Cre;Ghsrf/f mice resisted cold, maintaining a higher core body temperature at 4oC, showing higher expression of key thermogenic gene UCP1. Consistently, ex vivo study of white fat revealed increased lipolysis and glucose uptake. Aged aP2-Cre;Ghsrf/f mice also exhibited improved insulin sensitive and glucose tolerance. Thus while ectopic expression of aP2-Cre makes the phenotype interpretation challenging, the new results suggest that GHS-R in adipose tissues, but not muscle and pancreas, likely mediates the effects of GHS-R on adiposity and insulin sensitivity. |
| Keyword | GHS-R obesity insulin sensitivity aP2-Cre thermogenesis |
| Language | 英語English |
| The Source to Article | PB_Publication |
| PUB ID | 29012 |
| Document Type | Conference paper |
| Collection | Institute of Chinese Medical Sciences |
| Corresponding Author | Lin, L. |
| Recommended Citation GB/T 7714 | Lin, L.,Saito, K.,Lee, J.,et al. AP2-Cre mediated ablation of GHS-R reduces adiposity and improves insulin sensitivity[C], 2015. |
| APA | Lin, L.., Saito, K.., Lee, J.., Pradhan, G.., Xu, Y.., & Sun, Y. (2015). AP2-Cre mediated ablation of GHS-R reduces adiposity and improves insulin sensitivity. Cold Spring Harbor-Asia Conference. |
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