دورية أكاديمية
The metabolic syndrome and the hepatic fatty acid drainage hypothesis.
| العنوان: | The metabolic syndrome and the hepatic fatty acid drainage hypothesis. |
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| المؤلفون: | Berge RK; Institute of Medicine, The Lipid Research Group, Haukeland University Hospital, University of Bergen, 5021 Bergen, Norway. rolf.berge@med.uib.no, Tronstad KJ, Berge K, Rost TH, Wergedahl H, Gudbrandsen OA, Skorve J |
| المصدر: | Biochimie [Biochimie] 2005 Jan; Vol. 87 (1), pp. 15-20. |
| نوع المنشور: | Journal Article; Review |
| اللغة: | English |
| بيانات الدورية: | Publisher: Editions Scientifiques Elsevier Country of Publication: France NLM ID: 1264604 Publication Model: Print Cited Medium: Print ISSN: 0300-9084 (Print) Linking ISSN: 03009084 NLM ISO Abbreviation: Biochimie Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Paris : Editions Scientifiques Elsevier Original Publication: Paris. |
| مواضيع طبية MeSH: | Fatty Acids/*metabolism , Liver/*physiopathology , Metabolic Syndrome/*physiopathology, Animals ; Fatty Acids, Nonesterified/blood ; Humans ; Metabolic Syndrome/prevention & control ; Mitochondria, Liver/metabolism ; Obesity/physiopathology ; Oxidation-Reduction ; PPAR alpha/physiology ; Signal Transduction ; Sulfides/pharmacology ; Triglycerides/blood |
| مستخلص: | Much data indicates that lowering of plasma triglyceride levels by hypolipidemic agents is caused by a shift in the liver metabolism towards activation of peroxisome proliferator activated receptor (PPAR)alpha-regulated fatty acid catabolism in mitochondria. Feeding rats with lipid lowering agents leads to hypolipidemia, possibly by increased channeling of fatty acids to mitochondrial fatty acid oxidation at the expense of triglyceride synthesis. Our hypothesis is that increased hepatic fatty acid oxidation and ketogenesis drain fatty acids from blood and extrahepatic tissues and that this contributes significantly to the beneficial effects on fat mass accumulation and improved peripheral insulin sensitivity. To investigate this theory we employ modified fatty acids that change the plasma profile from atherogenic to cardioprotective. One of these novel agents, tetradecylthioacetic acid (TTA), is of particular interest due to its beneficial effects on lipid transport and utilization. These hypolipidemic effects are associated with increased fatty acid oxidation and altered energy state parameters of the liver. Experiments in PPAR alpha-null mice have demonstrated that the effects hypolipidemic of TTA cannot be explained by altered PPAR alpha regulation alone. TTA also activates the other PPARs (e.g., PPAR delta) and this might compensate for deficiency of PPAR alpha. Altogether, TTA-mediated clearance of blood triglycerides may result from a lowered level of apo C-III, with a subsequently induction of hepatic lipoprotein lipase activity and (re)uptake of fatty acids from very low density lipoprotein (VLDL). This is associated with an increased hepatic capacity for fatty acid oxidation, causing drainage of fatty acids from the blood stream. This can ultimately be linked to hypolipidemia, anti-adiposity, and improved insulin sensitivity. |
| Number of References: | 34 |
| المشرفين على المادة: | 0 (Fatty Acids) 0 (Fatty Acids, Nonesterified) 0 (PPAR alpha) 0 (Sulfides) 0 (Triglycerides) 7ZU5I25S2O (1-(carboxymethylthio)tetradecane) |
| تواريخ الأحداث: | Date Created: 20050301 Date Completed: 20050628 Latest Revision: 20220311 |
| رمز التحديث: | 20221213 |
| DOI: | 10.1016/j.biochi.2004.11.011 |
| PMID: | 15733731 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 0300-9084 |
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| DOI: | 10.1016/j.biochi.2004.11.011 |