Journal article
Mice lacking ARV1 have reduced signs of metabolic syndrome and non-alcoholic fatty liver disease
The Journal of biological chemistry, v 293(16), pp 5956-5974
20 Apr 2018
PMID: 29491146
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Metabolic syndrome (MetS) is a term used to characterize individuals having at least three of the following diseases: obesity, dyslipidemia, hyperglycemia, insulin resistance, hypertension, and nonalcoholic fatty liver disease (NAFLD). It is widespread, and the number of individuals with MetS is increasing. However, the events leading to the manifestation of MetS are not well-understood. Here, we show that loss of murine ARV1 (mARV1) results in resistance to acquiring diseases associated with MetS. Arv1−/− animals fed a high-fat diet were resistant to diet-induced obesity, had lower blood cholesterol and triglyceride levels, and retained glucose tolerance and insulin sensitivity. Livers showed no gross morphological changes, contained lower levels of cholesterol, triglycerides, and fatty acids, and showed fewer signs of NAFLD. Knockout animals had elevated levels of liver farnesol X receptor (FXR) protein and its target, small heterodimer protein (SHP). They also had decreased levels of CYP7α1, CYP8β1, and mature SREBP1 protein, evidence suggesting that liver FXR signaling was activated. Strengthening this hypothesis was the fact that peroxisome proliferator-activating receptor α (PPARα) protein was elevated, along with its target, fibroblast growth factor 21 (FGF21). Arv1−/− animals excreted more fecal cholesterol, free fatty acids, and bile acids. Their small intestines had 1) changes in bile acid composition, 2) an increase in the level of the intestinal FXR antagonist, tauromuricholic acid, and 3) showed signs of attenuated FXR signaling. Overall, we believe that ARV1 function is deleterious when consuming a high-fat diet. We further hypothesize that ARV1 is critical for initiating events required for the progression of diseases associated with MetS and NAFLD.
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Details
- Title
- Mice lacking ARV1 have reduced signs of metabolic syndrome and non-alcoholic fatty liver disease
- Creators
- Christina Gallo-Ebert - AnsysJamie Francisco - AnsysHsing-Yin Liu - AnsysRiley Draper - Hope CollegeKinnari Modi - AnsysMichael D. Hayward - AnsysBeverly K. Jones - AnsysOlesia Buiakova - AnsysVirginia McDonough - Hope CollegeJoseph T. Nickels - Rutgers, The State University of New Jersey
- Publication Details
- The Journal of biological chemistry, v 293(16), pp 5956-5974
- Publisher
- Elsevier
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Biochemistry and Molecular Biology
- Web of Science ID
- WOS:000430497300017
- Scopus ID
- 2-s2.0-85045854743
- Other Identifier
- 991021229987604721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Biochemistry & Molecular Biology