Journal article
Chronic Exposure to a High-Fat Diet Induces Hepatic Steatosis, Impairs Nitric Oxide Bioavailability, and Modifies the Mitochondrial Proteome in Mice
Antioxidants & redox signaling, Vol.15(2), pp.447-459
07/15/2011
DOI: 10.1089/ars.2010.3395
PMCID: PMC3118652
PMID: 20919931
Abstract
Obesity-related pathologies, such as nonalcoholic fatty liver disease, are linked to mitochondrial dysfunction and nitric oxide (NO) deficiency. Herein, we tested the hypothesis that a high-fat diet (HFD) modifies the liver mitochondrial proteome and alters proteins involved in NO metabolism, namely arginase 1 and endothelial NO synthase. Male C57BL/6 mice were fed a control or HID and liver mitochondria were isolated for proteornics and reactive oxygen species measurements. Steatosis and hepatocyte ballooning were present in livers of HFD mice, with no pathology observed in the controls. HFD mice had increased serum glucose and decreased adiponectin. Mitochondria] reactive oxygen species was increased after 8 weeks in the HFD mice, but decreased at 16 weeks compared with the control, which was accompanied by increased uncoupling protein 2. Using proteomics, 22 proteins were altered as a consequence of the HFD. This cohort consists of oxidative phosphorylation, lipid metabolism, sulfur amino acid metabolism, and chaperone proteins. We observed a HFD-dependent increase in arginase 1 and decrease in activated endothelial NO synthase. Serum and liver nitrate + nitrite were decreased by HFD. In summary, these data demonstrate that a HFD causes steatosis, alters NO metabolism, and modifies the liver mitochondrial proteome; thus, NO may play an important role in the processes responsible for nonalcoholic fatty liver disease. Antioxid. Redox Signal. 15,447-459.
Details
- Title: Subtitle
- Chronic Exposure to a High-Fat Diet Induces Hepatic Steatosis, Impairs Nitric Oxide Bioavailability, and Modifies the Mitochondrial Proteome in Mice
- Creators
- Heather B. Eccleston - University of Alabama at BirminghamKelly K. Andringa - University of Alabama at BirminghamAngela M. Betancourt - University of Alabama at BirminghamAdrienne L. King - University of Alabama at BirminghamSudheer K. Mantena - University of Alabama at BirminghamTelisha M. Swain - University of Alabama at BirminghamHeather N. Tinsley - University of Alabama at BirminghamRyan N. Nolte - University of Alabama at BirminghamTim R. Nagy - University of Alabama at BirminghamGary A. Abrams - Digestive & Liver Disease SpecialistsShannon M. Bailey - University of Alabama at Birmingham
- Resource Type
- Journal article
- Publication Details
- Antioxidants & redox signaling, Vol.15(2), pp.447-459
- Publisher
- Mary Ann Liebert, Inc
- DOI
- 10.1089/ars.2010.3395
- PMID
- 20919931
- PMCID
- PMC3118652
- ISSN
- 1523-0864
- eISSN
- 1557-7716
- Number of pages
- 13
- Grant note
- AA15172 / Research Supplement to Promote Diversity in Health-Related Research R01AA15172; R21DK73775; P30DK56336 / NIH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA P30AR050948 / UAB Skin Disease Research Center U54CA100949 / UAB Center for Nutrient-Gene Interaction in Cancer Prevention P30CA013148 / NATIONAL CANCER INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI) S10RR11329; S10RR13795 / NCRR; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Center for Research Resources (NCRR) P30CA13148 / UAB Comprehensive Cancer Center P50AT00477 / Purdue-UAB Botanicals Center for Age-Related Disease P50AT000477 / NATIONAL CENTER FOR COMPLEMENTARY &ALTERNATIVE MEDICINE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Center for Complementary & Alternative Medicine P30AR050948 / NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Arthritis & Musculoskeletal & Skin Diseases (NIAMS) P30DK074038 / 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) R01AA015172 / NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute on Alcohol Abuse & Alcoholism (NIAAA) P60DK79626 / UAB Diabetes Research and Training Center P30DK74038 / UAB Polycystic Kidney Disease Center S10RR011329 / NATIONAL CENTER FOR RESEARCH RESOURCES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Center for Research Resources (NCRR) UAB HSF General Endowment Fund
- Language
- English
- Date published
- 07/15/2011
- Academic Unit
- Orthopedics and Rehabilitation
- Record Identifier
- 9984548856602771
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