| Autor: |
Spitler KM; Department of Biochemistry, Fraternal Order of Eagles Diabetes Research Center, and Obesity Research and Education Initiative, University of Iowa, Iowa City, Iowa., Shetty SK; Department of Biochemistry, Fraternal Order of Eagles Diabetes Research Center, and Obesity Research and Education Initiative, University of Iowa, Iowa City, Iowa., Cushing EM; Department of Biochemistry, Fraternal Order of Eagles Diabetes Research Center, and Obesity Research and Education Initiative, University of Iowa, Iowa City, Iowa., Sylvers-Davie KL; Department of Biochemistry, Fraternal Order of Eagles Diabetes Research Center, and Obesity Research and Education Initiative, University of Iowa, Iowa City, Iowa., Davies BSJ; Department of Biochemistry, Fraternal Order of Eagles Diabetes Research Center, and Obesity Research and Education Initiative, University of Iowa, Iowa City, Iowa. |
| Abstrakt: |
Obesity is associated with dyslipidemia, ectopic lipid deposition, and insulin resistance. In mice, the global or adipose-specific loss of function of the protein angiopoietin-like 4 (ANGPTL4) leads to decreased plasma triglyceride levels, enhanced adipose triglyceride uptake, and protection from high-fat diet (HFD)-induced glucose intolerance. ANGPTL4 is also expressed highly in the liver, but the role of liver-derived ANGPTL4 is unclear. The goal of this study was to determine the contribution of hepatocyte ANGPTL4 to triglyceride and glucose homeostasis in mice during a high-fat diet challenge. We generated hepatocyte-specific ANGPTL4 deficient ( Angptl4 LivKO ) mice, fed them a 60% kcal/fat diet (HFD) for 6 mo and assessed triglyceride, liver, and glucose metabolic phenotypes. We also explored the effects of prolonged fasting on Angptl4 LivKO mice. The loss of hepatocyte-derived ANGPTL4 led to no major changes in triglyceride partitioning or lipoprotein lipase activity compared with control mice. Interestingly, although there was no difference in fasting plasma triglyceride levels after a 6 h fast, after an 18-h fast, normal chow diet-fed Angptl4 LivKO mice had lower triglyceride levels than control mice. On a HFD, Angptl4 LivKO mice initially showed no difference in glucose tolerance and insulin sensitivity, but improved glucose tolerance emerged in these mice after 6 mo on HFD. Our data suggest that hepatocyte ANGPTL4 does not directly regulate triglyceride partitioning, but that loss of liver-derived ANGPTL4 may be protective from HFD-induced glucose intolerance and influence plasma triglyceride (TG) metabolism during prolonged fasting. NEW & NOTEWORTHY 1 ) Angiopoietin-like 4 deficiency in hepatocytes ( Angptl4 LivKO ) does not improve triglyceride phenotypes during high-fat feeding. 2 ) Angptl4 LivKO mice have improved glucose tolerance after chronic high-fat diet. 3 ) Angptl4 LivKO mice have decreased fasting plasma triglyceride levels after an 18-h fast, but not after a 6-h fast. |
