title: Role of the fatty acid binding protein mal1 in obesity and insulin resistance.
abstract: The metabolic syndrome is a cluster of metabolic and inflammatory abnormalities including obesity, insulin resistance, type 2 diabetes, hypertension, dyslipidemia, and atherosclerosis. The fatty acid binding proteins aP2 (fatty acid binding protein [FABP]-4) and mal1 (FABP5) are closely related and both are expressed in adipocytes. Previous studies in aP2-deficient mice have indicated a significant role for aP2 in obesity-related insulin resistance, type 2 diabetes, and atherosclerosis. However, the biological functions of mal1 are not known. Here, we report the generation of mice with targeted null mutations in the mal1 gene as well as transgenic mice overexpressing mal1 from the aP2 promoter/enhancer to address the role of this FABP in metabolic regulation in the presence or absence of obesity. To address the role of the second adipocyte FABP in metabolic regulation in the presence and deficiency of obesity, absence of mal1 resulted in increased systemic insulin sensitivity in two models of obesity and insulin resistance. Adipocytes isolated from mal1-deficient mice also exhibited enhanced insulin-stimulated glucose transport capacity. In contrast, mice expressing high levels of mal1 in adipose tissue display reduced systemic insulin sensitivity. Hence, our results demonstrate that mal1 modulates adipose tissue function and contributes to systemic glucose metabolism and constitutes a potential therapeutic target in insulin resistance.
authors.affiliation: Division of Biological Sciences and Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts 02115, USA.
authors.forename: Kazuhisa
authors.initials: K
authors.lastname: Maeda
authors.forename: K Teoman
authors.initials: KT
authors.lastname: Uysal
authors.forename: Liza
authors.initials: L
authors.lastname: Makowski
authors.forename: Cem Z
authors.initials: CZ
authors.lastname: Görgün
authors.forename: Genichi
authors.initials: G
authors.lastname: Atsumi
authors.forename: Rex A
authors.initials: RA
authors.lastname: Parker
authors.forename: Jens
authors.initials: J
authors.lastname: Brüning
authors.forename: Ann Vogel
authors.initials: AV
authors.lastname: Hertzel
authors.forename: David A
authors.initials: DA
authors.lastname: Bernlohr
authors.forename: Gökhan S
authors.initials: GS
authors.lastname: Hotamisligil
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism*; D002352:Carrier Proteins; D003001:Cloning, Molecular; D003433:Crosses, Genetic; D004032:Diet; D050556:Fatty Acid-Binding Proteins; D005260:Female; D007333:Insulin Resistance / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009363:Neoplasm Proteins / Q000172:deficiency* / Q000235:genetics / Q000502:physiology*; D009765:Obesity / Q000097:blood / Q000235:genetics / Q000503:physiopathology*; D011401:Promoter Regions, Genetic; D020033:Protein Isoforms / Q000235:genetics
chemical_list: D001786:Blood Glucose; D002352:Carrier Proteins; C082667:Fabp5 protein, mouse; D050556:Fatty Acid-Binding Proteins; D009363:Neoplasm Proteins; D020033:Protein Isoforms