| First Author | Lu C | Year | 2013 |
| Journal | J Biol Chem | Volume | 288 |
| Issue | 22 | Pages | 15725-35 |
| PubMed ID | 23595986 | Mgi Jnum | J:199614 |
| Mgi Id | MGI:5503284 | Doi | 10.1074/jbc.M113.460212 |
| Citation | Lu C, et al. (2013) Targeted deletion of growth hormone (GH) receptor in macrophage reveals novel osteopontin-mediated effects of GH on glucose homeostasis and insulin sensitivity in diet-induced obesity. J Biol Chem 288(22):15725-35 |
| abstractText | We investigated GH action on macrophage (MPhi) by creating a MPhi-specific GH receptor-null mouse model (MacGHR KO). On a normal diet (10% fat), MacGHR KO and littermate controls exhibited similar growth profiles and glucose excursions on intraperitoneal glucose (ipGTT) and insulin tolerance (ITT) tests. However, when challenged with high fat diet (HFD, 45% fat) for 18 weeks, MacGHR KO mice exhibited impaired ipGTT and ITT compared with controls. In MacGHR KO, adipose-tissue (AT) MPhi abundance was increased with skewing toward M1 polarization. Expression of pro-inflammatory cytokines (IL1beta, TNF-alpha, IL6, and osteopontin (OPN)) were increased in MacGHR KO AT stromal vascular fraction (SVF). In MacGHR KO AT, crown-like-structures were increased with decreased insulin-dependent Akt phosphorylation. The abundance of phosphorylated NF-kappaB and of OPN was increased in SVF and bone-marrow-derived MPhi in MacGHR KO. GH, acting via an NF-kappaB site in the distal OPN promoter, inhibited the OPN promoter. Thus in diet-induced obesity (DIO), lack of GH action on the MPhi exerts an unexpected deleterious effect on glucose homeostasis by accentuating AT inflammation and NF-kappaB-dependent activation of OPN expression. These novel results in mice support the possibility that administration of GH could have salutary effects on DIO-associated chronic inflammation and insulin resistance in humans. |
