title: Adipocyte-specific inactivation of Acyl-CoA synthetase fatty acid transport protein 4 (Fatp4) in mice causes adipose hypertrophy and alterations in metabolism of complex lipids under high fat diet.
abstract: Fatp4 exhibits acyl-CoA synthetase activity and is thereby able to catalyze the activation of fatty acids for further metabolism. However, its actual function in most tissues remains unresolved, and its role in cellular fatty acid uptake is still controversial. To characterize Fatp4 functions in adipocytes in vivo, we generated a mouse line with adipocyte-specific inactivation of the Fatp4 gene (Fatp4(A-/-)). Under standard conditions mutant mice showed no phenotypical aberrance. Uptake of radiolabeled palmitic and lignoceric acid into adipose tissue of Fatp4(A-/-) mice was unchanged. When exposed to a diet enriched in long chain fatty acids, Fatp4(A-/-) mice gained more body weight compared with control mice, although they were not consuming more food. Pronounced obesity was accompanied by a thicker layer of subcutaneous fat and greater adipocyte circumference, although expression of genes involved in de novo lipogenesis was not changed. However, the increase in total fat mass was contrasted by a significant decrease in various phospholipids, sphingomyelin, and cholesteryl esters in adipocytes. Livers of Fatp4-deficient animals under a high fat diet exhibited a higher degree of fatty degeneration. Nonetheless, no evidence for changes in insulin sensitivity and adipose inflammation was found. In summary, the results of this study confirm that Fatp4 is not crucial for fatty acid uptake into adipocytes. Instead, under the condition of a diet enriched in long chain fatty acids, adipocyte-specific Fatp4 deficiency results in adipose hypertrophy and profound alterations in the metabolism of complex lipids.
authors.affiliation: Department of Internal Medicine IV, University of Heidelberg, 69120 Heidelberg.
authors.forename: Lena-Solveig
authors.initials: LS
authors.lastname: Lenz
authors.affiliation: Department of Internal Medicine IV, University of Heidelberg, 69120 Heidelberg.
authors.forename: Jana
authors.initials: J
authors.lastname: Marx
authors.affiliation: Department of Internal Medicine IV, University of Heidelberg, 69120 Heidelberg.
authors.forename: Walee
authors.initials: W
authors.lastname: Chamulitrat
authors.affiliation: Department of Internal Medicine IV, University of Heidelberg, 69120 Heidelberg.
authors.forename: Iris
authors.initials: I
authors.lastname: Kaiser
authors.affiliation: Department of Cellular and Molecular Pathology, German Cancer Research Center, 69120 Heidelberg.
authors.forename: Hermann-Josef
authors.initials: HJ
authors.lastname: Gröne
authors.affiliation: Institute of Clinical Chemistry, University of Regensburg, 93042 Regensburg.
authors.forename: Gerhard
authors.initials: G
authors.lastname: Liebisch
authors.affiliation: Institute of Clinical Chemistry, University of Regensburg, 93042 Regensburg.
authors.forename: Gerd
authors.initials: G
authors.lastname: Schmitz
authors.affiliation: Department of Internal Medicine, St. Elisabeth Hospital, 46225 Dorsten.
authors.forename: Christoph
authors.initials: C
authors.lastname: Elsing
authors.affiliation: Department of General Pathology, Institute of Pathology, 69120 Heidelberg.
authors.forename: Beate K
authors.initials: BK
authors.lastname: Straub
authors.affiliation: Department of Internal Medicine IV, University of Heidelberg, 69120 Heidelberg.
authors.forename: Joachim
authors.initials: J
authors.lastname: Füllekrug
authors.affiliation: Department of Internal Medicine IV, University of Heidelberg, 69120 Heidelberg.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Stremmel
authors.affiliation: Department of Internal Medicine IV, University of Heidelberg, 69120 Heidelberg; Department of Internal Medicine I, Klinikum Idar-Oberstein, 55743 Idar-Oberstein, Germany. Electronic address: dr._thomas_herrmann@email.de.
authors.forename: Thomas
authors.initials: T
authors.lastname: Herrmann
mesh_terms: D017667:Adipocytes / Q000201:enzymology* / Q000473:pathology; D000273:Adipose Tissue / Q000201:enzymology* / Q000473:pathology; D000818:Animals; D004041:Dietary Fats / Q000009:adverse effects* / Q000494:pharmacology; D050612:Fatty Acid Transport Proteins / Q000235:genetics / Q000378:metabolism*; D005227:Fatty Acids / Q000235:genetics / Q000378:metabolism*; D006984:Hypertrophy; D050356:Lipid Metabolism / Q000187:drug effects* / Q000235:genetics; D008099:Liver / Q000201:enzymology / Q000473:pathology; D008107:Liver Diseases / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout
chemical_list: D004041:Dietary Fats; D050612:Fatty Acid Transport Proteins; D005227:Fatty Acids; C493572:Slc27a4 protein, mouse