These authors contributed equally to the work.
Steatohepatitis/Metabolic Liver Disease
Article first published online: 4 DEC 2012
Copyright © 2012 American Association for the Study of Liver Diseases
Volume 56, Issue 6, pages 2154–2162, December 2012
How to Cite
Lian, J., Wei, E., Wang, S. P., Quiroga, A. D., Li, L., Di Pardo, A., van der Veen, J., Sipione, S., Mitchell, G. A. and Lehner, R. (2012), Liver specific inactivation of carboxylesterase 3/triacylglycerol hydrolase decreases blood lipids without causing severe steatosis in mice. Hepatology, 56: 2154–2162. doi: 10.1002/hep.25881
Potential conflict of interest: Nothing to report.
The Lipid Analysis Core received financial support from the Women and Children Health Research Institute. A. D. P. was supported by a studentship from the Alberta Heritage Foundation for Medical Research. A. D. Q. was supported by a fellowship from the Heart and Stroke Foundation of Canada. S. S. and R.L. are a Scholar and a Scientist, respectively, of the Alberta Heritage Foundation for Medical Research. S. S. is a Canada Research Chair in Neurobiology of Huntington Disease. This work was supported by operating grants from the Canadian Institutes of Health Research (69043 to R. L., 111219 to S. S., and 221920 to G. A. M.) and the Canadian Diabetes Association (to J. v. d. V.) and a Pfizer CardioVascular Award (to R. L.).
- Issue published online: 4 DEC 2012
- Article first published online: 4 DEC 2012
- Accepted manuscript online: 18 JUN 2012 04:56AM EST
- Manuscript Accepted: 2 MAY 2012
- Manuscript Received: 8 NOV 2011
- Women and Children Health Research Institute
- Alberta Heritage Foundation
- Heart and Stroke Foundation of Canada
- Alberta Heritage Foundation for Medical Research
- Canada Research Chair in Neurobiology of Huntington Disease
- Canadian Institutes of Health Research. Grant Numbers: 69043, 111219, 221920
- Canadian Diabetes Association
- Pfizer CardioVascular Award
Carboxylesterase 3/triacylglycerol hydrolase (Ces3/TGH) participates in hepatic very low-density lipoprotein (VLDL) assembly and in adipose tissue basal lipolysis. Global ablation of Ces3/Tgh expression decreases serum triacylglycerol (TG) and nonesterified fatty acid levels and improves insulin sensitivity. To understand the tissue-specific role of Ces3/TGH in lipid and glucose homeostasis, we generated mice with a liver-specific deletion of Ces3/Tgh expression (L-TGH knockout [KO]). Elimination of hepatic Ces3/Tgh expression dramatically decreased plasma VLDL TG and VLDL cholesterol concentrations but only moderately increased liver TG levels in mice fed a standard chow diet. Significantly reduced plasma TG and cholesterol without hepatic steatosis were also observed in L-TGH KO mice challenged with a high-fat, high-cholesterol diet. L-TGH KO mice presented with increased plasma ketone bodies and hepatic fatty acid oxidation. Intrahepatic TG in L-TGH KO mice was stored in significantly smaller lipid droplets. Augmented hepatic TG levels in chow-fed L-TGH KO mice did not affect glucose tolerance or glucose production from hepatocytes, but impaired insulin tolerance was observed in female mice. Conclusion: Our data suggest that ablation of hepatic Ces3/Tgh expression decreases plasma lipid levels without causing severe hepatic steatosis. (HEPATOLOGY 2012;56:2154–2162)