Cold-Induced Changes in Gene Expression in Brown Adipose Tissue: Implications for the Activation of Thermogenesis

Abstract

Brown adipose tissue (BAT) is the site of heat production (thermogenesis). This unique function is performed by uncoupling protein 1 (UCP1) specifically expressed in mitochondria of BAT. UCP1 dissipates the driving force of ATP synthesis, and thus causes heat production followed by energy expenditure. The thermogenic function of BAT has the role of maintaining body temperature under cold conditions. When animals are exposed to cold, the expression of UCP1 gene is increased to activate thermogenesis. To date, functional analysis of BAT has been focused on UCP1, because it plays an indispensable role in thermogenesis. However, the gene expression of not only UCP1 but also that of other genes in BAT is expected to be regulated to achieve effective thermogenesis. Our previous investigations showed increased expression of genes that encode several energy metabolic enzymes in the BAT of rats kept in the cold. These changes in gene expression imply that the enhancement of energy metabolism is needed to activate thermogenesis. Furthermore, various reports from studies focused on genes whose expression is changed in response to cold stimulation have provided new insights into the function of BAT. In this review, to understand the thermogenic function of BAT systematically, we have provided an overview of previous findings on changes in the expression of genes thought to be related to the activation of thermogenesis in BAT.

Negative correlation between milk production and brown adipose tissue gene expression in lactating mice

“…Previous studies have shown that gene expression of Fabp3 in the BAT of non-breeding rats is induced by cold exposure and reduced at high ambient temperatures, closely resembling the expression profile of UCP1 (Watanabe et al, 2008;Yamashita et al, 2008). These changes in Fabp3 expression were confirmed at the protein level, indicating an essential role of Fabp3 in fatty acid transport and its oxidation through the activity of UCP1 in cold-induced thermogenesis (Yamashita et al, 2008).…”

Isoleucine or valine deprivation stimulates fat loss via increasing energy expenditure and regulating lipid metabolism in WAT

“…Alternatively, it may also be possible that valine deprivation has a direct effect on thermotaxic center. Thus, one of the adaptive changes occurs at this case is to increase UCP1 expression in BAT, thereby to maintain normal body temperature, as many studies reported for the function of UCP1 (Watanabe et al 2008;Enerback et al 1997). Both possibilities, however, will be investigated in the future.…”

Adipose triglyceride lipase expression and fasting regulation are differently affected by cold exposure in adipose tissues of lean and obese Zucker rats

“…Therefore, it would be expected that after a longer period of cold exposure, optimal adaptation to this environment would be achieved, and thus, an increase in food intake would be observed. Cold stimulus increases sympathetic activity, and the catecholamines released from sympathetic innervations, acting mainly through β3 adrenergic receptors, stimulate lipolysis (and fatty acid release) in WAT and BAT and thermogenesis in BAT [35,36]. Detailed in vivo and in vitro studies have suggested an important role of ATGL in lipid mobilization in response to cold stimuli and isoproterenol treatment [10,12].…”