Altered Hepatic Lipid Metabolism Contributes to Nonalcoholic Fatty Liver Disease in Leptin-Deficient Ob/Ob Mice
Nonalcoholic fatty liver disease (NAFLD) is strongly linked to obesity, insulin resistance, and abnormal hepatic lipid metabolism; however, the precise regulation of these processes remains poorly understood. Here we examined genes and proteins involved in hepatic oxidation and lipogenesis in 14-wee...
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| Format: | Article |
| Language: | English |
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Wiley
2013-01-01
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| Series: | Journal of Obesity |
| Online Access: | http://dx.doi.org/10.1155/2013/296537 |
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| author | James W. Perfield Laura C. Ortinau R. Taylor Pickering Meghan L. Ruebel Grace M. Meers R. Scott Rector |
| author_facet | James W. Perfield Laura C. Ortinau R. Taylor Pickering Meghan L. Ruebel Grace M. Meers R. Scott Rector |
| author_sort | James W. Perfield |
| collection | DOAJ |
| description | Nonalcoholic fatty liver disease (NAFLD) is strongly linked to obesity, insulin resistance, and abnormal hepatic lipid metabolism; however, the precise regulation of these processes remains poorly understood. Here we examined genes and proteins involved in hepatic oxidation and lipogenesis in 14-week-old leptin-deficient Ob/Ob mice, a commonly studied model of obesity and hepatic steatosis. Obese Ob/Ob mice had increased fasting glucose, insulin, and calculated HOMA-IR as compared with lean wild-type (WT) mice. Ob/Ob mice also had greater liver weights, hepatic triglyceride (TG) content, and markers of de novo lipogenesis, including increased hepatic gene expression and protein content of acetyl-CoA carboxylase (ACC), fatty acid synthase (FAS), and stearoyl-CoA desaturase-1 (SCD-1), as well as elevated gene expression of PPARγ and SREBP-1c compared with WT mice. While hepatic mRNA levels for PGC-1α, PPARα, and TFAM were elevated in Ob/Ob mice, measures of mitochondrial function (β-HAD activity and complete (to CO2) and total mitochondrial palmitate oxidation) and mitochondrial OXPHOS protein subunits I, III, and V content were significantly reduced compared with WT animals. In summary, reduced hepatic mitochondrial content and function and an upregulation in de novo lipogenesis contribute to obesity-associated NAFLD in the leptin-deficient Ob/Ob mouse. |
| format | Article |
| id | doaj-art-dfd04a80b8ba4c819ca06bb83bc95b6c |
| institution | Kabale University |
| issn | 2090-0708 2090-0716 |
| language | English |
| publishDate | 2013-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Obesity |
| spelling | doaj-art-dfd04a80b8ba4c819ca06bb83bc95b6c2025-02-03T05:46:58ZengWileyJournal of Obesity2090-07082090-07162013-01-01201310.1155/2013/296537296537Altered Hepatic Lipid Metabolism Contributes to Nonalcoholic Fatty Liver Disease in Leptin-Deficient Ob/Ob MiceJames W. Perfield0Laura C. Ortinau1R. Taylor Pickering2Meghan L. Ruebel3Grace M. Meers4R. Scott Rector5Department of Nutrition and Exercise Physiology, University of Missouri, Columbia, MO 65211, USADepartment of Nutrition and Exercise Physiology, University of Missouri, Columbia, MO 65211, USADepartment of Nutrition and Exercise Physiology, University of Missouri, Columbia, MO 65211, USADivision of Gastroenterology and Hepatology, Department of Internal Medicine, University of Missouri, Columbia, MO 65211, USADivision of Gastroenterology and Hepatology, Department of Internal Medicine, University of Missouri, Columbia, MO 65211, USADepartment of Nutrition and Exercise Physiology, University of Missouri, Columbia, MO 65211, USANonalcoholic fatty liver disease (NAFLD) is strongly linked to obesity, insulin resistance, and abnormal hepatic lipid metabolism; however, the precise regulation of these processes remains poorly understood. Here we examined genes and proteins involved in hepatic oxidation and lipogenesis in 14-week-old leptin-deficient Ob/Ob mice, a commonly studied model of obesity and hepatic steatosis. Obese Ob/Ob mice had increased fasting glucose, insulin, and calculated HOMA-IR as compared with lean wild-type (WT) mice. Ob/Ob mice also had greater liver weights, hepatic triglyceride (TG) content, and markers of de novo lipogenesis, including increased hepatic gene expression and protein content of acetyl-CoA carboxylase (ACC), fatty acid synthase (FAS), and stearoyl-CoA desaturase-1 (SCD-1), as well as elevated gene expression of PPARγ and SREBP-1c compared with WT mice. While hepatic mRNA levels for PGC-1α, PPARα, and TFAM were elevated in Ob/Ob mice, measures of mitochondrial function (β-HAD activity and complete (to CO2) and total mitochondrial palmitate oxidation) and mitochondrial OXPHOS protein subunits I, III, and V content were significantly reduced compared with WT animals. In summary, reduced hepatic mitochondrial content and function and an upregulation in de novo lipogenesis contribute to obesity-associated NAFLD in the leptin-deficient Ob/Ob mouse.http://dx.doi.org/10.1155/2013/296537 |
| spellingShingle | James W. Perfield Laura C. Ortinau R. Taylor Pickering Meghan L. Ruebel Grace M. Meers R. Scott Rector Altered Hepatic Lipid Metabolism Contributes to Nonalcoholic Fatty Liver Disease in Leptin-Deficient Ob/Ob Mice Journal of Obesity |
| title | Altered Hepatic Lipid Metabolism Contributes to Nonalcoholic Fatty Liver Disease in Leptin-Deficient Ob/Ob Mice |
| title_full | Altered Hepatic Lipid Metabolism Contributes to Nonalcoholic Fatty Liver Disease in Leptin-Deficient Ob/Ob Mice |
| title_fullStr | Altered Hepatic Lipid Metabolism Contributes to Nonalcoholic Fatty Liver Disease in Leptin-Deficient Ob/Ob Mice |
| title_full_unstemmed | Altered Hepatic Lipid Metabolism Contributes to Nonalcoholic Fatty Liver Disease in Leptin-Deficient Ob/Ob Mice |
| title_short | Altered Hepatic Lipid Metabolism Contributes to Nonalcoholic Fatty Liver Disease in Leptin-Deficient Ob/Ob Mice |
| title_sort | altered hepatic lipid metabolism contributes to nonalcoholic fatty liver disease in leptin deficient ob ob mice |
| url | http://dx.doi.org/10.1155/2013/296537 |
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