Effect of premature aging on murine adipose tissue

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.

► Reduced appetite in Bmal1−/− mice is associated with reduced expression of PPARα. ► Bmal1−/− mice do not show increased white and brown fat mass with aging. ► Adipocyte and blood vessel size and density are not affected by Bmal1 deficiency. ► Bmal1 gene deletion is associated with marked downregulation of PAI-1 in white fat. ► Premature aging induces marked downregulation of leptin in adipose tissues.