Overexpression of APOC1 in obob mice leads to hepatic steatosis and severe hepatic insulin resistance
| Autor: | Johannes A. Romijn, Peter J. Voshol, Anita M. van den Hoek, Martin Muurling, Ronald P. Mensink, Louis M. Havekes, T. Hanno Pijl |
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| Přispěvatelé: | Other departments, Gaubius Instituut TNO, Humane Biologie, RS: NUTRIM School of Nutrition and Translational Research in Metabolism |
| Jazyk: | angličtina |
| Rok vydání: | 2004 |
| Předmět: |
Lipid storage
Blood Glucose Biomedical Research Mouse Glucose transport medicine.medical_treatment Glucose blood level Gene Expression Gene Biochemistry Hepatic fat accumulation Animal tissue rosiglitazone chemistry.chemical_compound Gene overexpression Hyperinsulinemia Mice Endocrinology lipid metabolism Insulin APOC1 gene Fatty liver Fatty Acids Triacylglycerol blood level free fatty acid metabolism Cholesterol blood level Hyperlipidemia peroxisome proliferator-activated receptor-γ Insulin blood level Ketone bodies Free fatty acid metabolism Diacylglycerol Rosiglitazone medicine.drug medicine.medical_specialty Weight reduction Adipose tissue Hyperlipidemias Mice Transgenic QD415-436 Biology Triacylglycerol Insulin resistance Transgenic mouse Internal medicine Peroxisome proliferator activated receptor gamma Hyperinsulinism medicine Animals Humans Animal model Animal experiment Obesity Apolipoproteins C Peroxisome proliferator-activated receptor-γ Ketone body Apolipoprotein C-I Triglyceride Body Weight Gluconeogenesis Cell Biology medicine.disease Nonhuman Fatty Liver Lipid metabolism Glucose chemistry Fatty acid metabolism Hyperglycemia hepatic fat accumulation Steatosis Insulin Resistance Controlled study |
| Zdroj: | Journal of Lipid Research, Vol 45, Iss 1, Pp 9-16 (2004) Journal of lipid research, 45(1), 9-16. American Society for Biochemistry and Molecular Biology Inc. Journal of Lipid Research, 1, 45, 9-16 Journal of Lipid Research, 45(1), 9-16. American Society for Biochemistry and Molecular Biology, Inc. |
| ISSN: | 0022-2275 |
| Popis: | Obese obob mice with strong overexpression of the human apolipoprotein C1 (APOC1) exhibit excessive free fatty acid (FFA) and triglyceride (TG) levels and severely reduced body weight (due to the absence of subcutaneous adipose tissue) and skin abnormalities. To evaluate the effects of APOC1 overexpression on hepatic and peripheral insulin sensitivity in a less-extreme model, we generated obob mice with mild overexpression of APOC1 (obob/APOC1+/-) and performed hyperinsulinemic clamp analysis. Compared with obob littermates, obob/APOC1+/- mice showed reduced body weight (-25%) and increased plasma levels of TG (+632%), total cholesterol (+134%), FFA (+65%), glucose (+73%, and insulin (+49%). Hyperinsulinemic clamp analysis revealed severe whole-body and hepatic insulin resistance in obob/APOC1+/- mice and, in addition, increased hepatic uptake of FFA and hepatic TG content. Treatment of obob/APOC1+/- mice with rosiglitazone strongly improved whole-body insulin sensitivity as well as hepatic insulin sensitivity, despite a further increase of hepatic fatty acid (FA) uptake and a panlobular increase of hepatic TG accumulation. We conclude that overexpression of APOC1 prevents rosiglitazone-induced peripheral FA uptake leading to severe hepatic steatosis. Interestingly, despite rosiglitazone-induced hepatic steatosis, hepatic insulin sensitivity improves dramatically. We hypothesize that the different hepatic fat accumulation and/or decrease in FA intermediates has a major effect on the insulin sensitivity of the liver. Chemicals / CAS: glucose, 50-99-7, 84778-64-3; insulin, 9004-10-8; rosiglitazone, 122320-73-4, 155141-29-0; Apolipoprotein C-I; Apolipoproteins C; Blood Glucose; Fatty Acids; Insulin, 11061-68-0 |
| Databáze: | OpenAIRE |
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