title: The impact of ageing on adipose structure, function and vasculature in the B6D2F1 mouse: evidence of significant multisystem dysfunction.
abstract: The critical influence of the white adipose tissue (WAT) on metabolism is well-appreciated in obesity, but adipose tissue dysfunction as a mechanism underlying age-associated metabolic dysfunction requires elucidation. To explore this possibility, we assessed metabolism and measures of epididymal (e)WAT mitochondria and artery function in young (6.1 ± 0.4 months) and old (29.6 ± 0.2 months) B6D2F1 mice. There were no group differences in average daily oxygen consumption, fasted blood glucose or plasma free fatty acids, but fasted plasma insulin and the homeostatic model assessment of insulin resistance (HOMA-IR%) were higher in the old (∼50-85%, P < 0.05). Tissue mass (P < 0.05) and adipocyte area were lower (∼60%) (P < 0.01) and fibrosis was greater (sevenfold, P < 0.01) in eWAT with older age. The old also exhibited greater liver triglycerides (∼60%, P < 0.05). The mitochondrial respiratory oxygen flux after the addition of glutamate and malate (GM), adenosine diphosphate (d), succinate (S) and octanoyl carnitine (O) were one- to twofold higher in eWAT of old mice (P < 0.05). Despite no change in the respiratory control ratio, substrate control ratios of GMOd/GMd and GMOSd/GMd were ∼30-40% lower in old mice (P < 0.05) and were concomitant with increased nitrotyrosine (P < 0.05) and reduced expression of brown adipose markers (P < 0.05). Ageing reduced vascularity (∼50%, P < 0.01), angiogenic capacity (twofold, P < 0.05) and expression of vascular endothelial growth factor (∼50%, P < 0.05) in eWAT. Finally, endothelium-dependent dilation was lower (P < 0.01) in isolated arteries from eWAT arteries of the old mice. Thus, metabolic dysfunction with advancing age occurs in concert with dysfunction in the adipose tissue characterized by both mitochondrial and arterial dysfunction.
authors.affiliation: Division of Geriatrics, Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City, UT, USA Geriatrics Research Education and Clinical Center, Veteran's Affairs Medical Center-Salt Lake City, Salt Lake City, UT, USA Department of Exercise and Sports Science, University of Utah, Salt Lake City, UT, USA.
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Donato
authors.affiliation: Department of Exercise and Sports Science, University of Utah, Salt Lake City, UT, USA.
authors.forename: Grant D
authors.initials: GD
authors.lastname: Henson
authors.affiliation: Department of Exercise and Sports Science, University of Utah, Salt Lake City, UT, USA.
authors.forename: Corey R
authors.initials: CR
authors.lastname: Hart
authors.affiliation: Division of Geriatrics, Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City, UT, USA.
authors.forename: Gwenael
authors.initials: G
authors.lastname: Layec
authors.affiliation: Division of Geriatrics, Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City, UT, USA.
authors.forename: Joel D
authors.initials: JD
authors.lastname: Trinity
authors.affiliation: Division of Geriatrics, Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City, UT, USA.
authors.forename: R Colton
authors.initials: RC
authors.lastname: Bramwell
authors.affiliation: Division of Geriatrics, Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City, UT, USA.
authors.forename: Ryley A
authors.initials: RA
authors.lastname: Enz
authors.affiliation: Division of Geriatrics, Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City, UT, USA.
authors.forename: R Garrett
authors.initials: RG
authors.lastname: Morgan
authors.affiliation: Division of Geriatrics, Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City, UT, USA.
authors.forename: Kelly D
authors.initials: KD
authors.lastname: Reihl
authors.affiliation: Division of Geriatrics, Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City, UT, USA.
authors.forename: Sugata
authors.initials: S
authors.lastname: Hazra
authors.affiliation: Division of Geriatrics, Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City, UT, USA.
authors.forename: Ashley E
authors.initials: AE
authors.lastname: Walker
authors.affiliation: Division of Geriatrics, Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City, UT, USA Geriatrics Research Education and Clinical Center, Veteran's Affairs Medical Center-Salt Lake City, Salt Lake City, UT, USA Department of Exercise and Sports Science, University of Utah, Salt Lake City, UT, USA.
authors.forename: Russell S
authors.initials: RS
authors.lastname: Richardson
authors.affiliation: Division of Geriatrics, Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City, UT, USA Geriatrics Research Education and Clinical Center, Veteran's Affairs Medical Center-Salt Lake City, Salt Lake City, UT, USA Department of Exercise and Sports Science, University of Utah, Salt Lake City, UT, USA lisa.lesniewski@utah.edu.
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Lesniewski
mesh_terms: D000273:Adipose Tissue / Q000098:blood supply / Q000254:growth & development / Q000378:metabolism* / Q000502:physiology; D000375:Aging / Q000378:metabolism* / Q000502:physiology; D000818:Animals; D001158:Arteries / Q000378:metabolism / Q000502:physiology; D001835:Body Weight; D002331:Carnitine / Q000031:analogs & derivatives / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism; D008293:Malates / Q000378:metabolism; D008297:Male; D051379:Mice; D008928:Mitochondria / Q000378:metabolism; D018919:Neovascularization, Physiologic; D018384:Oxidative Stress; D010101:Oxygen Consumption; D019802:Succinic Acid / Q000378:metabolism; D014280:Triglycerides / Q000378:metabolism; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism; D014664:Vasodilation
chemical_list: D008293:Malates; D014280:Triglycerides; C002744:3-nitrotyrosine; D018698:Glutamic Acid; D014443:Tyrosine; C030298:malic acid; D019802:Succinic Acid; C008698:octanoylcarnitine; D002331:Carnitine