The study reveals the mechanism by which Sirtuin 7 suppresses thermogenesis in mice



Mammals convert energy stored in adipose tissue into heat via a process known as thermogenesis. This process is regulated by a family of signaling proteins called sirtuins. A recent study by researchers from Kumamoto University revealed the mechanism by which the Sirtuin 7 protein suppresses thermogenesis in mice. These findings may pave the way for new therapies targeting diseases caused by metabolic disorders.

Mammals regulate their internal body temperature by converting energy stored as fat in adipose tissue into heat. Brown adipose tissue (BAT) plays an important role in this process, which is defined as tissue thermogenesis. Heat generation in BAT must be tightly regulated because heat production is beneficial in some circumstances, such as cold environments, but harmful in others, such as during hunger or sleep. The balance between suppressing and activating BAT thermogenesis also has long-term effects on factors such as BMI and glucose levels in adult humans. This fine regulation of thermogenesis in BAT is largely controlled by a family of signaling proteins called sirtuins. Previous literature has shown that sirtuins 1–6 (SIRT1–6) facilitate BAT thermogenesis, but to date, there has been little information about the role played by the seventh member of the family, sirtuin 7 (SIRT7).

Now, in a new study published in nature connections, The researchers revealed that SIRT7 suppresses BAT thermogenesis in mice. As part of their study, they bred multiple strains of “Sirt7 knockout mice,” that is, mice that had been genetically modified not to produce or to produce non-functional SIRT7. They found that mice knocked out of the Sirt7 diet showed higher body temperatures and higher energy expenditure than their counterparts with SIRT7. “Although several sirtuins are positively involved in regulating BAT functions, we revealed that SIRT7 plays an opposite role in BAT thermogenesis. Our results showed that SIRT7 deficiency in brown adipose cells (fat cells) results in increased energy expenditure in all From in vitro and in vivo., commented Professor Tatsuya Yoshizawa of Kumamoto University in Japan, lead author of the paper.

Mammals often go through phases of reduced activity, such as torpor or hibernation; A shorter version of hibernation lasts for hours when food is scarce. Mice’s body temperature drops dramatically during hibernation to conserve energy. However, in the study, SIRT7-knockout mice had significantly higher temperatures than wild-type mice during this stage. The results indicate that SIRT7 helps mice reduce energy loss during periods of regular activity, as well as periods of reduced metabolic activity.

The study also revealed that SIRT7 affects thermogenesis by reducing the production of another protein, non-duplex protein 1 (UCP1). UCP1 is a positive thermogenesis regulator that facilitates the conversion of energy into heat. The researchers noted that the out-of-control mice in the study had a much higher concentration of this protein than the wild-type mice. They also explored the molecular pathway by which SIRT7 repressed the expression of UCP1, which specifically involves an intermediate protein called insulin-like mRNA-binding protein 2 (IMP2).

Our findings reveal that SIRT7 demethylates IMP2. Degraded IMP2 binds much more strongly to Ucp1 mRNA, thus preventing its translation into UCP1 protein, and thus BAT thermogenesis. “

Professor Tatsuya Yoshizawa, Kumamoto University

BAT thermogenesis is generally accepted to have health benefits, particularly for individuals who consume nutrients in excess, or suffer from obesity or other metabolic disorders. Recent studies indicate that it also contributes to the development and progression of hypermetabolic conditions, such as cancer, burns, and infectious diseases. The results of this study, specifically with regard to SIRT7 as a key regulator of thermogenesis in BAT, will find application in the development of novel targets and therapies for the treatment of these diseases and disorders.

Source:

Journal reference:

Yoshizawa, T.; et al. (2022) SIRT7 inhibits energy expenditure and thermogenesis by regulating brown adipose tissue functions in mice. Nature Communications. doi.org/10.1038/s41467-022-35219-z.



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