UCP1 deficiency increases susceptibility to diet‐induced obesity with age

Abstract

SummaryLoss 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 β β β β 3-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 cAMPdependent 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 β β 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.

Brown and beige fat: development, function and therapeutic potential

“…This is thought to conceal the effect of brown fat and Ucp1 on energy balance. Consistent with this idea, old Ucp1-deficient mice, which are larger and less cold sensitive than npg younger mice, become obese even at ambient temperature 57 . The marked impact of temperature on physiology has been overlooked by much of the rodent research community.…”

Effect of Nicotine and Ephedrine on the Accumulation of 18F-FDG in Brown Adipose Tissue

“…BAT is the main organ that produces diet-induced thermogenesis, and a lack of its function is considered to be one cause of obesity (18). Other reports have said that uncoupling protein 1 doubleknock-out mice displayed increased susceptibility to dietinduced obesity with age (19). Recently, BAT has also been found to be important in understanding the mechanism of glucose tolerance (20,21).…”

Role of sex hormones in modulation of brown adipose tissue activity

“…Indeed, an increased propensity for obesity has been found in both young (Feldmann et al 2009) and old mice (Kontani et al 2005) lacking UCP1 activity. Recent results from studies on genetically modified mice have consistently shown that an increased BAT amount protects from body weight gain and metabolic dysregulation induced by high fat feeding (Cederberg et al 2001, Seale et al 2011.…”