title: Brown Adipose Tissue Function Is Enhanced in Long-Lived, Male Ames Dwarf Mice.
abstract: Ames dwarf mice (Prop1df/df) are long-lived due to a loss of function mutation, resulting in deficiency of GH, TSH, and prolactin. Along with a marked extension of longevity, Ames dwarf mice have improved energy metabolism as measured by an increase in their oxygen consumption and heat production, as well as a decrease in their respiratory quotient. Along with alterations in energy metabolism, Ames dwarf mice have a lower core body temperature. Moreover, Ames dwarf mice have functionally altered epididymal white adipose tissue (WAT) that improves, rather than impairs, their insulin sensitivity due to a shift from pro- to anti-inflammatory cytokine secretion. Given the unique phenotype of Ames dwarf epididymal WAT, their improved energy metabolism, and lower core body temperature, we hypothesized that Ames dwarf brown adipose tissue (BAT) may function differently from that of their normal littermates. Here we use histology and RT-PCR to demonstrate that Ames dwarf mice have enhanced BAT function. We also use interscapular BAT removal to demonstrate that BAT is necessary for Ames dwarf energy metabolism and thermogenesis, whereas it is less important for their normal littermates. Furthermore, we show that Ames dwarf mice are able to compensate for loss of interscapular BAT by using their WAT depots as an energy source. These findings demonstrate enhanced BAT function in animals with GH and thyroid hormone deficiencies, chronic reduction of body temperature, and remarkably extended longevity.
authors.affiliation: Department of Internal Medicine (J.D., S.M., Y.F., J.A.H., C.Z., A.B.), Geriatric Research, and Department of Medical Microbiology, Immunology, and Cell Biology (J.D., A.B.), Southern Illinois University School of Medicine, Springfield, Illinois 62702; Institute of Cardiovascular Disease (C.Z.), Key Laboratory for Arteriosclerology of Hunan Province, University of South China, Hengyang 421001, People's Republic of China; and Department of Biology (L.Y.S.), University of Alabama at Birmingham, Birmingham, Alabama 35294.
authors.forename: Justin
authors.initials: J
authors.lastname: Darcy
authors.affiliation: Department of Internal Medicine (J.D., S.M., Y.F., J.A.H., C.Z., A.B.), Geriatric Research, and Department of Medical Microbiology, Immunology, and Cell Biology (J.D., A.B.), Southern Illinois University School of Medicine, Springfield, Illinois 62702; Institute of Cardiovascular Disease (C.Z.), Key Laboratory for Arteriosclerology of Hunan Province, University of South China, Hengyang 421001, People's Republic of China; and Department of Biology (L.Y.S.), University of Alabama at Birmingham, Birmingham, Alabama 35294.
authors.forename: Samuel
authors.initials: S
authors.lastname: McFadden
authors.affiliation: Department of Internal Medicine (J.D., S.M., Y.F., J.A.H., C.Z., A.B.), Geriatric Research, and Department of Medical Microbiology, Immunology, and Cell Biology (J.D., A.B.), Southern Illinois University School of Medicine, Springfield, Illinois 62702; Institute of Cardiovascular Disease (C.Z.), Key Laboratory for Arteriosclerology of Hunan Province, University of South China, Hengyang 421001, People's Republic of China; and Department of Biology (L.Y.S.), University of Alabama at Birmingham, Birmingham, Alabama 35294.
authors.forename: Yimin
authors.initials: Y
authors.lastname: Fang
authors.affiliation: Department of Internal Medicine (J.D., S.M., Y.F., J.A.H., C.Z., A.B.), Geriatric Research, and Department of Medical Microbiology, Immunology, and Cell Biology (J.D., A.B.), Southern Illinois University School of Medicine, Springfield, Illinois 62702; Institute of Cardiovascular Disease (C.Z.), Key Laboratory for Arteriosclerology of Hunan Province, University of South China, Hengyang 421001, People's Republic of China; and Department of Biology (L.Y.S.), University of Alabama at Birmingham, Birmingham, Alabama 35294.
authors.forename: Joshua A
authors.initials: JA
authors.lastname: Huber
authors.affiliation: Department of Internal Medicine (J.D., S.M., Y.F., J.A.H., C.Z., A.B.), Geriatric Research, and Department of Medical Microbiology, Immunology, and Cell Biology (J.D., A.B.), Southern Illinois University School of Medicine, Springfield, Illinois 62702; Institute of Cardiovascular Disease (C.Z.), Key Laboratory for Arteriosclerology of Hunan Province, University of South China, Hengyang 421001, People's Republic of China; and Department of Biology (L.Y.S.), University of Alabama at Birmingham, Birmingham, Alabama 35294.
authors.forename: Chi
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Department of Internal Medicine (J.D., S.M., Y.F., J.A.H., C.Z., A.B.), Geriatric Research, and Department of Medical Microbiology, Immunology, and Cell Biology (J.D., A.B.), Southern Illinois University School of Medicine, Springfield, Illinois 62702; Institute of Cardiovascular Disease (C.Z.), Key Laboratory for Arteriosclerology of Hunan Province, University of South China, Hengyang 421001, People's Republic of China; and Department of Biology (L.Y.S.), University of Alabama at Birmingham, Birmingham, Alabama 35294.
authors.forename: Liou Y
authors.initials: LY
authors.lastname: Sun
authors.affiliation: Department of Internal Medicine (J.D., S.M., Y.F., J.A.H., C.Z., A.B.), Geriatric Research, and Department of Medical Microbiology, Immunology, and Cell Biology (J.D., A.B.), Southern Illinois University School of Medicine, Springfield, Illinois 62702; Institute of Cardiovascular Disease (C.Z.), Key Laboratory for Arteriosclerology of Hunan Province, University of South China, Hengyang 421001, People's Republic of China; and Department of Biology (L.Y.S.), University of Alabama at Birmingham, Birmingham, Alabama 35294.
authors.forename: Andrzej
authors.initials: A
authors.lastname: Bartke
mesh_terms: D002001:Adipose Tissue, Brown / Q000378:metabolism*; D000818:Animals; D001823:Body Composition / Q000235:genetics; D001831:Body Temperature / Q000235:genetics; D002153:Calorimetry, Indirect; D004734:Energy Metabolism / Q000235:genetics*; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism; D007333:Insulin Resistance / Q000235:genetics*; D008136:Longevity / Q000235:genetics*; D008297:Male; D051379:Mice; D009154:Mutation; D022722:Thermogenesis / Q000235:genetics*
chemical_list: D018398:Homeodomain Proteins; C102134:Prophet of Pit-1 protein