title: Effect of premature aging on murine adipose tissue.
abstract: To evaluate the effect of aging on adipose tissue development, subcutaneous (SC) and gonadal (GON) white and peri-aortic brown adipose tissues were analyzed of 10 and 30 week old mice deficient in the clock gene Bmal1 (brain and muscle arnt like protein 1) (Bmal1(-/-)) and wild-type littermates (Bmal1(+/+)) kept on a standard fat diet. At both ages, daily food intake was significantly decreased for Bmal1(-/-) mice, associated with reduced hypothalamic expression of PPARα. Between 10 and 30 weeks of age, the total body weight of Bmal1(+/+) mice increased significantly, but that of Bmal1(-/-) mice did not change. Whereas for Bmal1(+/+) mice, both SC and GON fat mass increased with age, these decreased for Bmal1(-/-) mice. This was associated with increased adipocyte size with age for Bmal1(+/+) but not for Bmal1(-/-) mice. Adipose tissue related angiogenesis was not affected by genotype or aging. Peri-aortic brown adipose tissue mass in 30 week old Bmal1(-/-) mice was significantly reduced as compared to age-matched Bmal1(+/+) mice. Comparison of gene expression profiles in SC and GON adipose tissues of both genotypes revealed very marked effects of Bmal1 gene deletion in itself on PAI-1 (4- to 13-fold downregulation), whereas the associated effect of premature aging was striking for leptin (90- to 130-fold downregulation). Thus, premature aging in Bmal1(-/-) mice kept on normal chow was associated with reduced adiposity.
authors.affiliation: Center for Molecular and Vascular Biology, Katholieke Universiteit Leuven, 3000 Leuven, Belgium.
authors.forename: Bianca
authors.initials: B
authors.lastname: Hemmeryckx
authors.forename: Marc F
authors.initials: MF
authors.lastname: Hoylaerts
authors.forename: H Roger
authors.initials: HR
authors.lastname: Lijnen
mesh_terms: D056930:ARNTL Transcription Factors / Q000172:deficiency / Q000235:genetics; D017667:Adipocytes / Q000473:pathology; D000273:Adipose Tissue / Q000098:blood supply / Q000254:growth & development* / Q000378:metabolism; D002001:Adipose Tissue, Brown / Q000098:blood supply / Q000254:growth & development* / Q000378:metabolism; D052436:Adipose Tissue, White / Q000098:blood supply / Q000254:growth & development* / Q000378:metabolism; D050154:Adiposity / Q000502:physiology; D000375:Aging / Q000378:metabolism / Q000502:physiology; D019588:Aging, Premature / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001808:Blood Vessels / Q000473:pathology; D048429:Cell Size; D004195:Disease Models, Animal; D004435:Eating / Q000502:physiology; D015870:Gene Expression; D020869:Gene Expression Profiling / Q000379:methods; D008055:Lipids / Q000097:blood; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D015430:Weight Gain / Q000502:physiology
chemical_list: D056930:ARNTL Transcription Factors; C538961:Bmal1 protein, mouse; D001786:Blood Glucose; D008055:Lipids