Differential regulation of uncoupling protein gene homologues in multiple tissues of hibernating ground squirrels

Abstract

Nonshivering thermogenesis in brown adipose tissue (BAT) provides heat through activation of a mitochondrial uncoupling protein (UCP1), which causes futile electron transport cycles without the production of ATP. Recent discovery of two molecular homologues, UCP2, expressed in multiple tissues, and UCP3, expressed in muscle, has resulted in investigation of their roles in thermoregulatory physiology and energy balance. To determine the expression pattern of Ucp homologues in hibernating mammals, we compared relative mRNA levels of Ucp1, -2, and -3 in BAT, white adipose tissue (WAT), and skeletal muscle of arctic ground squirrels ( Spermophilus parryii) hibernating at different ambient and body temperatures, with levels determined in tissues from ground squirrels not in hibernation. Here we report significant increases in mRNA levels for Ucp2 in WAT (1.6-fold) and Ucp3 in skeletal muscle (3-fold) during hibernation. These results indicate the potential for a role of UCP2 and UCP3 in thermal homeostasis during hibernation and indicate that parallel mechanisms and multiple tissues could be important for nonshivering thermoregulation in mammals.

Neuronal UCP1 expression suggests a mechanism for local thermogenesis during hibernation

“…Similar to thirteen-lined ground squirrels (their close relative), arctic ground squirrels may potentially rely on UCP1 to support the integrity and function of the nervous system during deep torpor. In this case, however, UCP1 expression should be seasonal, as shown here for the thirteen-lined ground squirrels, because an earlier study did not detect UCP1 transcripts in the brain of active arctic ground squirrels (42). It will be interesting, therefore, to evaluate the expression of UCP1 transcripts and protein in torpid animals.…”

Arousal from hibernation and BAT thermogenesis against cold: central mechanism and molecular basis

“…A partial list of changes in gene expression associated with hibernation includes: increased alpha-globulin mRNA and protein (Srere et al, 1992) and decreased hibernation-related proteins (Takamatsu et al, 1993) in liver, increased UCP-1 mRNA in BAT (Boyer et al, 1998;Liu et al, 1998;Hashimoto et al, 1999b), increased lipase and UCP-2 mRNA in white adipose tissue (Wilson et al, 1992;Boyer et al, 1998), increased glyceraldehyde-3-phosphate dehydrogenase and UCP-3 mRNA in skeletal muscle (Soukri et al, 1996;Boyer et al, 1998), increased pancreatic lipase mRNA and protein and pyruvate dehydrogenase kinase mRNA and protein in heart (Andrews et al, 1998), increased in early immediate genes and decreased prostaglandin synthase mRNA in brain (O'Hara et al, 1999) and increased c-Fos in SCN of the hypothalamus and neuropeptide Y mRNA in the arcuate nucleus (Bitting et al, 1994;El Ouezzani et al, 2001). …”

“…Changes of the level of expression of UCP-1 mRNA and homologues (UCP-2, UCP-3) in BAT during hibernation were measured in arctic ground squirrels (Boyer et al, 1998), in Daurian ground squirrels (Liu et al, 1998;Liu et al, 2001) and in golden hamsters (Fig.5) . In each species, UCP-1-mRNA levels in BAT removed from hibernating animals, with body temperatures near freezing, were increased relative to the summer active animals but were not significantly different from cold acclimated animals.…”

Biochemical aspects of the uncoupling proteins: View from the chair

“…The up regulation of UCP3 mRNA in muscle of hibernating ground squirrels suggests a role for UCP3 at low temperatures. 6 (9) Further research to answer the question whether development of obesity is associated with altered functioning of one or more of the UCPs.…”