Nonalcoholic fatty liver disease (NAFLD) is the most common chronic fatty liver disease worldwide, particularly in obese and type 2 diabetic individuals. Currently, there are no therapies for NAFLD that have been approved by the US Food and Drug Administration. Herein, we examine the rationale for using ω3 polyunsaturated fatty acids (PUFAs) in NAFLD therapy. This focus is based on the finding that NAFLD severity is associated with a reduction of hepatic C ω3 PUFAs. Because C ω3 PUFAs are pleiotropic regulators of cell function, loss of C ω3 PUFAs has the potential to significantly impact hepatic function. We describe NAFLD prevalence and pathophysiology as well as current NAFLD therapies. We also present evidence from clinical and preclinical studies that evaluated the capacity of C ω3 PUFAs to treat NAFLD. Given the clinical and preclinical evidence, dietary C ω3 PUFA supplementation has the potential to decrease human NAFLD severity by reducing hepatosteatosis and liver injury.
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http://dx.doi.org/10.1146/annurev-nutr-061021-030223 | DOI Listing |
J Gerontol A Biol Sci Med Sci
November 2007
Department of Physiology, University of Granada, Granada, Spain.
This study investigates aging-related changes in lipid peroxidation and functionality in liver and skeletal-muscle mitochondria in rats fed a diet rich in polyunsaturated fatty acids (PUFA), depending on supplementation or not with coenzyme Q(10) (CoQ(10)). Two groups of rats were fed for 24 months on a PUFA-rich diet, differing in supplementation or not with CoQ(10). At 6 and 24 months mitochondria were analyzed for fatty acid profile; hydroperoxides; alpha-tocopherol; CoQ(9;) CoQ(10;) cytochromes b, c+c(1), and a+a(3) contents; cytochrome c oxidase activity; and catalase activity in cytosol.
View Article and Find Full Text PDFBiochemistry
July 2006
Department of Biochemistry and Biophysics, The Arrhenius Laboratories for Natural Sciences, Stockholm University, SE-106 91 Stockholm, Sweden.
The major proton-transfer pathway into the buried active site of cytochrome c oxidase (CcO) is the D-pathway that begins with the subunit I residue Asp-132 on the inner protein surface (the cytoplasmic surface of the aa3-type CcO of Rhodobacter sphaeroides). Asp-132 is surrounded by residues from both subunits I and III. In the absence of subunit III, CcO retains activity, but the functional characteristics of the D-pathway are significantly altered such that the transfer of protons from Asp-132 into the pathway becomes the rate-limiting step.
View Article and Find Full Text PDFBiochemistry
September 2005
Department of Biochemistry and Chemistry, University of Illinois at Urbana-Champaign, 600 South Mathews Avenue, Urbana, Illinois 61801, USA.
Cytochrome c oxidase uses the free energy of oxygen reduction to establish a transmembrane proton gradient. The proton-conducting D-channel in this enzyme is the major input pathway for protons which go to the binuclear center for water formation ("chemical protons") and likely the only input pathway for protons that get translocated across the lipid membrane ("pumped protons"). The D-channel starts at an acidic residue near the protein surface (D132, Rhodobacter sphaeroides numbering) and leads to another acidic residue near the binuclear center.
View Article and Find Full Text PDFJ Gerontol A Biol Sci Med Sci
August 2005
Institute of Nutrition and Food Technology, Department of Physiology, University of Granada, Spain.
Coenzyme Q(10) supplementation on age-related changes in oxidative stress and function of heart mitochondria in rats fed a polyunsaturated fatty acid (PUFA)-rich diet was investigated. Two groups of rats were fed for 24 months on a PUFA-rich diet, differing in supplementation or not with coenzyme Q(10). Animals were killed at 6, 12, or 24 months.
View Article and Find Full Text PDFFree Radic Biol Med
July 1999
Department of Biochemistry and Molecular Biology and C.N.R. Unit for the Study of Mitochondria and Bioenergetics, University of Bari, Italy.
Ischemia-reperfusion injury to cardiac myocytes involves membrane damage mediated by oxygen free radicals. Lipid peroxidation is considered a major mechanism of oxygen free radical toxicity in reperfused heart. Mitochondrial respiration is an important source of these reactive oxygen species and hence a potential contributor to reperfusion injury.
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