Journal article
Liver Perilipin 5 Expression Worsens Hepatosteatosis But Not Insulin Resistance in High Fat-Fed Mice
Molecular endocrinology (Baltimore, Md.), Vol.29(10), pp.1414-1425
10/01/2015
DOI: 10.1210/me.2015-1069
PMCID: PMC4588733
PMID: 26296152
Abstract
Perilipin 5 (PLIN5) is a lipid droplet (LD) protein highly expressed in oxidative tissues, including the fasted liver. However, its expression also increases in nonalcoholic fatty liver. To determine whether PLIN5 regulates metabolic phenotypes of hepatosteatosis under nutritional excess, liver targeted overexpression of PLIN5 was achieved using adenoviral vector (Ad-PLIN5) in male C57BL/6J mice fed high-fat diet. Mice treated with adenovirus expressing green fluorescent protein (GFP) (Ad-GFP) served as control. Ad-PLIN5 livers increased LD in the liver section, and liquid chromatography with tandem mass spectrometry revealed increases in lipid classes associated with LD, including triacylglycerol, cholesterol ester, and phospholipid classes, compared with Ad-GFP liver. Lipids commonly associated with hepatic lipotoxicity, diacylglycerol, and ceramides, were also increased in Ad-PLIN5 liver. The expression of genes in lipid metabolism regulated by peroxisome proliferator-activated receptor-alpha was reduced suggestive of slower mobilization of stored lipids in Ad-PLIN5 mice. However, the increase of hepatosteatosis by PLIN5 overexpression did not worsen glucose homeostasis. Rather, serum insulin levels were decreased, indicating better insulin sensitivity in Ad-PLIN5 mice. Moreover, genes associated with liver injury were unaltered in Ad-PLIN5 steatotic liver compared with Ad-GFP control. Phosphorylation of protein kinase B was increased in Ad-PLIN5-transduced AML12 hepatocyte despite of the promotion of fatty acid incorporation to triacylglycerol as well. Collectively, our data indicates that the increase in liver PLIN5 during hepatosteatosis drives further lipid accumulation but does not adversely affect hepatic health or insulin sensitivity.
Details
- Title: Subtitle
- Liver Perilipin 5 Expression Worsens Hepatosteatosis But Not Insulin Resistance in High Fat-Fed Mice
- Creators
- Michelle B. Trevino - Eastern Virginia Medical SchoolDavid Mazur-Hart - Eastern Virginia Medical SchoolYui Machida - Eastern Virginia Medical SchoolTimothy King - Eastern Virginia Medical SchoolJoseph Nadler - Eastern Virginia Medical SchoolElena V. Galkina - Eastern Virginia Medical SchoolArjun Poddar - Old Dominion UniversitySucharita Dutta - Eastern Virginia Medical SchoolYumi Imai - Eastern Virginia Medical School
- Resource Type
- Journal article
- Publication Details
- Molecular endocrinology (Baltimore, Md.), Vol.29(10), pp.1414-1425
- Publisher
- Oxford Univ Press
- DOI
- 10.1210/me.2015-1069
- PMID
- 26296152
- PMCID
- PMC4588733
- ISSN
- 0888-8809
- eISSN
- 1944-9917
- Number of pages
- 12
- Grant note
- R01DK090490 / NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK) R01-DK090490; R01-DK090490-02W1 / National Institutes of Health; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA
- Language
- English
- Date published
- 10/01/2015
- Academic Unit
- Endocrinology and Metabolism; Internal Medicine
- Record Identifier
- 9984359918402771
Metrics
12 Record Views