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SHR Neuro Krebs Kardio Lipid Stoffw Microb

Wagner, EM; Kratky, D; Haemmerle, G; Hrzenjak, A; Kostner, GM; Steyrer, E; Zechner, R.
Defective uptake of triglyceride-associated fatty acids in adipose tissue causes the SREBP-1c-mediated induction of lipogenesis.
J LIPID RES. 2004; 45(2): 356-365. Doi: 10.1194/jlr.M300293-JLR200 [OPEN ACCESS]
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Co-Autor*innen der Med Uni Graz
Hrzenjak Andelko
Kostner Gerhard
Kratky Dagmar
Steyrer Ernst
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Abstract:
Lipoprotein lipase (LPL) is the only known enzyme in the capillary endothelium of peripheral tissues that hydrolizes plasma triglycerides and provides fatty acids (FAs) for their subsequent tissue uptake. Previously, we demonstrated that mice that express LPL exclusively in muscle develop essentially normal fat mass despite the absence of LPL and the deprivation of nutritionally derived FAs in adipose tissue (AT). Using this mouse model, we now investigated the metabolic response to LPL deficiency in AT that enables maintenance of normal AT mass. We show that the rate of FA production was 1.8-fold higher in LPL-deficient AT than in control AT. The levels of mRNA and enzymatic activities of important enzymes involved in FA and triglyceride biosynthesis were induced concomitantly. Increased plasma glucose clearing and (14)C-deoxyglucose uptake into LPL-deficient mouse fat pads indicated that glucose provided the carbon source for lipid synthesis. Leptin expression was decreased in LPL-deficient AT. Finally, the induction of de novo FA synthesis in LPL-deficient AT was associated with increased expression and processing of sterol regulatory element binding protein 1 (SREBP-1), together with an increase in INSIG-1 expression. These results suggest that in the absence of LPL in AT, lipogenesis is activated through increased SREBP-1 expression and processing triggered by decreased availability of nutrition-derived FAs, elevated insulin, and low leptin levels.
Find related publications in this database (using NLM MeSH Indexing)
Adipose Tissue - metabolism
Animals - metabolism
Animals, Genetically Modified - metabolism
CCAAT-Enhancer-Binding Proteins - genetics
DNA-Binding Proteins - genetics
Diet - genetics
Endothelium - metabolism
Fatty Acids - metabolism
Gene Expression Regulation, Enzymologic - physiology
Humans - physiology
Insulin - metabolism
Leptin - metabolism
Lipids - biosynthesis
Lipoprotein Lipase - genetics
Mice - genetics
Muscles - metabolism
Sterol Regulatory Element Binding Protein 1 - metabolism
Transcription Factors - metabolism
Triglycerides - metabolism

Find related publications in this database (Keywords)
fatty acid biosynthesis
lipoprotein lipase
lipogenic enzymes
sterol regulatory element binding protein
insulin-induced gene
leptin
polyunsaturated fatty acid
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