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UCP1 deficiency increases susceptibility to diet‐induced obesity with age

2005; Wiley; Volume: 4; Issue: 3 Linguagem: Inglês

10.1111/j.1474-9726.2005.00157.x

1474-9726

Yasuhide Kontani, Yifan Wang, Kazuhiro Kimura, Ken-ichi Inokuma, Masayuki Saito, T. Suzuki‐Miura, Z. Wang, Yoshifumi Sato, Naoki Mori, Hitoshi Yamashita,

Diet and metabolism studies

Summary Loss of nonshivering thermogenesis in mice by inactivation of the mitochondrial uncoupling protein gene ( Ucp1 −/– mice) causes increased sensitivity to cold and unexpected resistance to diet‐induced obesity at a young age. To clarify the role of UCP1 in body weight regulation throughout life and influence of UCP1 deficiency on longevity, we longitudinally analyzed the phenotypes of Ucp1 −/– mice maintained in a room at 23 °C. There was no difference in body weight and lifespan between genotypes under the standard chow diet condition, whereas the mutant mice developed obesity with age under the high‐fat (HF) diet condition. Compared with Ucp1 +/+ mice, Ucp1 −/– mice showed increased expression of genes related to thermogenesis and fatty acid metabolism, such as β3‐adrenergic receptor, in adipose tissues of the 3‐month‐old mutants; however, the augmented expression was reduced in Ucp1 +/+ mice in 11‐month‐old Ucp1 −/– mice fed the HF diet. Likewise, the increased levels of UCP3 and cAMP‐dependent protein kinase in the brown adipose tissue of Ucp1 −/– mice given the standard diet were decreased significantly in that of Ucp1 −/– mice fed the HF diet, which animals showed impaired norepinephrine‐induced lipolysis in their adipose tissues. These results suggest profound attenuation of β‐adrenergic responsiveness and fatty acid utilization in Ucp1 −/– mice fed the HF diet, bringing them to late‐onset obesity. Our findings provide evidence that UCP1 is neither essential for body weight regulation nor for longevity under conditions of standard diet and normal housing temperature, but deficiency increases susceptibility to obesity with age in combination with HF diet.