期刊论文详细信息
Nutrition & Metabolism
Control of lipid metabolism by adipocyte FGFR1-mediated adipohepatic communication during hepatic stress
Yongde Luo5  Wallace L McKeehan5  Fen Wang1  Weimin He4  Chengliu Jin2  Min Ye1  Cong Wang3  Chaofeng Yang1 
[1] Center for Cancer and Stem Cell Biology, Institute of Biosciences and Technology, Texas A&M Health Science Center, 2121 W. Holcombe Blvd, Houston, TX, 77030-3303, USA;Department of Animal Resources, Georgia State University, Atlanta, GA, 30303, USA;School of Pharmaceutical Science, Wenzhou Medical College, Wenzhou, 325035, China;Center for Cardiovascular Diseases, Texas Southern University, Houston, TX, 77004, USA;IBT Proteomics and Nanotechnology Laboratory, Institute of Biosciences and Technology, Texas A&M Health Science Center, 2121 W. Holcombe Blvd, Houston, TX, 77030-3303, USA
关键词: Starvation;    Lipid metabolism;    Hepatic stress;    Hepatic steatosis;    FGFR;    Fibroblast growth factor receptor;    FGF;    Fibroblast growth factor;    Adipose tissue;   
Others  :  811863
DOI  :  10.1186/1743-7075-9-94
 received in 2012-08-07, accepted in 2012-10-25,  发布年份 2012
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【 摘 要 】

Background

Endocrine FGF19 and FGF21 exert their effects on metabolic homeostasis through fibroblast growth factor receptor (FGFR) and co-factor betaKlotho (KLB). Ileal FGF19 regulates bile acid metabolism through specifically FGFR4-KLB in hepatocytes where FGFR1 is not significant. Both FGF19 and FGF21 activate FGFR1-KLB whose function predominates in adipocytes. Recent studies using administration of FGF19 and FGF21 and genetic ablation of KLB or adipocyte FGFR1 indicate that FGFR1-KLB mediates the response of adipocytes to both FGF21 and FGF19. Here we show that adipose FGFR1 regulates lipid metabolism through direct effect on adipose tissue and indirect effects on liver under starvation conditions that cause hepatic stress.

Methods

We employed adipocyte-specific ablations of FGFR1 and FGFR2 genes in mice, and analyzed metabolic consequences in adipose tissue, liver and systemic parameters under normal, fasting and starvation conditions.

Results

Under normal conditions, the ablation of adipose FGFR1 had little effect on adipocytes, but caused shifts in expression of hepatic genes involved in lipid metabolism. Starvation conditions precipitated a concurrent elevation of serum triglycerides and non-esterified fatty acids, and increased hepatic steatosis and adipose lipolysis in the FGFR1-deficient mice. Little effect on glucose or ketone bodies due to the FGFR1 deficiency was observed.

Conclusions

Our results suggest an adipocyte-hepatocyte communication network mediated by adipocyte FGFR1 that concurrently dampens hepatic lipogenesis and adipocyte lipolysis. We propose that this serves overall to mete out and extend lipid reserves for neural fuels (glucose and ketone bodies), while at the same time governing extent of hepatosteatosis during metabolic extremes and other conditions causing hepatic stress.

【 授权许可】

   
2012 Yang et al.; licensee BioMed Central Ltd.

【 预 览 】
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