Increased Hepatic CD36 Expression Contributes to Dyslipidemia Associated With Diet-Induced Obesity
| Autor: | Jason R.B. Dyck, Debby P.Y. Koonen, Martin E. Young, René L. Jacobs, Huy Ong, Carrie Lynn M Soltys, Maria Febbraio, Dennis E. Vance |
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| Rok vydání: | 2007 |
| Předmět: |
CD36 Antigens
medicine.medical_specialty Endocrinology Diabetes and Metabolism CD36 Palmitic Acid Type 2 diabetes Biology Mice Internal medicine Diabetes mellitus Internal Medicine medicine Animals Secretion Obesity Cells Cultured Dyslipidemias Mice Knockout chemistry.chemical_classification Glucose tolerance test medicine.diagnostic_test Fatty Acids nutritional and metabolic diseases Fatty acid Glucose Tolerance Test medicine.disease Mice Inbred C57BL Endocrinology Liver chemistry Hepatocytes biology.protein Energy Intake Dyslipidemia Lipoprotein |
| Zdroj: | Diabetes. 56:2863-2871 |
| ISSN: | 1939-327X 0012-1797 |
| Popis: | OBJECTIVE—The etiology of type 2 diabetes often involves diet-induced obesity (DIO), which is associated with elevated plasma fatty acids and lipoprotein associated triglycerides. Since aberrant hepatic fatty acid uptake may contribute to this, we investigated whether increased expression of a fatty acid transport protein (CD36) in the liver during DIO contributes to the dyslipidemia that precedes development of type 2 diabetes. RESEARCH DESIGN AND METHODS—We determined the effect DIO has on hepatic CD36 protein expression and the functional consequence of this in terms of hepatic triglyceride storage and secretion. In addition, in vivo adenoviral gene delivery of CD36 to the livers of lean mice was performed to determine if increased hepatic CD36 protein was sufficient to alter hepatic fatty acid uptake and triglyceride storage and secretion. RESULTS—During DIO, CD36 protein levels in the liver are significantly elevated, and these elevated levels correlate with increased hepatic triglyceride storage and secretion. These alterations in liver lipid storage and secretion were also observed upon forced expression of hepatic CD36 in the absence of DIO and were accompanied with a marked rise in hepatic fatty acid uptake in vivo, demonstrating that increased CD36 expression is sufficient to recapitulate the aberrant liver lipid handling observed in DIO. CONCLUSIONS—Increased expression of hepatic CD36 protein in response to DIO is sufficient to exacerbate hepatic triglyceride storage and secretion. As these CD36-mediated effects contribute to the dyslipidemia that often precedes the development of type 2 diabetes, increased hepatic CD36 expression likely plays a causative role in the pathogenesis of type 2 diabetes. |
| Databáze: | OpenAIRE |
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