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Exploring the effects of FATP2 gene deletion on fatty acid‐responsive gene expression in liver
Author(s) -
Gabell Jeffrey T,
Perez Vincent,
Black Paul,
DiRusso Concetta
Publication year - 2019
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2019.33.1_supplement.488.5
Subject(s) - cd36 , lipotoxicity , biology , fatty acid , medicine , endocrinology , gene expression , adipocyte protein 2 , fatty acid binding protein , fatty liver , fatty acid metabolism , biochemistry , gene , insulin resistance , insulin , disease
Fatty Acid Transport Protein 2 (FATP2) is highly expressed in the small intestine, liver, kidney, pancreas, and placenta. FATP2 has two activities: [1] it facilitates the uptake of long chain fatty acids into the cell and [2] it activates very long chain fatty acids destined for incorporation into cellular lipids or β‐oxidation. Previous work from this laboratory implicates FATP2 activity in the promotion of lipotoxicity that may lead to cell death. The present studies employ mice lacking the FATP2 gene (FATP2 −/− ) to more fully understand the function and effects of FATP2‐dependent fatty acid uptake on liver metabolism and lipotoxic disease. We hypothesize a reduction in uptake and metabolism of fatty acids dependent upon FATP2 may lead to alterations in expression of genes that are responsive to exogenous fatty acids. Gene expression was measured in wild type and FATP2 −/− livers using quantitative PCR and validated using western blots to assess the impact of genotype, diet, and fasting period. Preliminary data shows that expression of FABP1, CD36, Cyp4A10, and ACOX are elevated in livers of FATP2 −/− mice independent of dietary fat levels. In contrast, expression of NPC1L1 was decreased. Differences between diets alone resulted in an increase in FABP2 and FABP4, FAS, Serpinb6 and ApoB expression, while FABP1, CD36, and ACOX expression was dependent on both genotype and diet. These results further suggest deletion of FATP2 increases PPAR a signaling, perhaps through increases in a native fatty acid ligand. Overall, these studies further demonstrate an important role for FATP2 in liver lipid homeostasis during high fat dietary challenge. This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .