Journal article
Chronic high-fat feeding and prolonged fasting in liver-specific ANGPTL4 knockout mice
American journal of physiology: endocrinology and metabolism, Vol.321(4), pp.E464-E478
10/01/2021
DOI: 10.1152/ajpendo.00144.2021
PMCID: PMC8560380
PMID: 34396783
Abstract
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.
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.
Details
- Title: Subtitle
- Chronic high-fat feeding and prolonged fasting in liver-specific ANGPTL4 knockout mice
- Creators
- Kathryn M. Spitler - University of IowaShwetha K. Shetty - University of IowaEmily M. Cushing - University of IowaKelli L. Sylvers-Davie - University of IowaBrandon S. J. Davies - University of Iowa
- Resource Type
- Journal article
- Publication Details
- American journal of physiology: endocrinology and metabolism, Vol.321(4), pp.E464-E478
- DOI
- 10.1152/ajpendo.00144.2021
- PMID
- 34396783
- PMCID
- PMC8560380
- ISSN
- 0193-1849
- eISSN
- 1522-1555
- Grant note
- DOI: 10.13039/100000050, name: HHS | NIH | National Heart, Lung, and Blood Institute, award: R01HL130146
- Language
- English
- Date published
- 10/01/2021
- Academic Unit
- Fraternal Order of Eagles Diabetes Research Center; Biochemistry and Molecular Biology; Health and Human Physiology
- Record Identifier
- 9984293084702771
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