Brown adipocytes have attracted much attention because of their capacity to counteract obesity and metabolic disease.
Wang et al from the lab of Prof. PEI Gang at Institute of Biochemistry and Cell Biology (SIBCB), Shanghai Institutes for Biological Sciences (SIBS), Chinese Academy of Sciences (CAS) found that β-arrestin-1 contributes to brown adipose tissue (BAT) function. Further studies showed that β-arrestin-1 directly interacts with PPARa/γ and modulates their transcriptional activities, providing potential regulatory pathway for BAT function. This work was published in Scientific Reports.
In contrast to white adipose tissue (WAT), which is specialized for the storage of excess energy, brown adipose tissue (BAT) contributes to energy expenditure and adaptive thermogenesis. Cold exposure leads to the stimulation of β-adrenergic receptors in brown adipocytes, resulting in the activation of oxidative phosphorylation and thermogenic activity. This process is facilitated by the increased expression of mitochondrial uncoupling protein-1 (UCP1), which uncouples substrate oxidation from ATP production so that heat is produced. New drugs or polypeptides that increase differentiation or activity of BAT in adult humans might offer new treatments for obesity and diabetes. As major regulators in metabolism, PPARs play critical regulatory roles in regulating brown fat adipogenesis and function.
β-arrestins function mainly by binding to diverse partners and play critical roles in various signaling pathways and physiological procedures. Under the guidance of Prof. PEI Gang, ZHAO Jian and ZHOU zhaocai, graduate student WANG Congcong found that β-arrestin-1 knock-out mice show enhanced cold tolerance and increased thermogenic gene expression. Moreover, by biolayer interferometry assay and nuclear magnetic resonance (NMR) spectroscopy analysis, the author found that β-arrestin-1 directly interacts with PPARa and PPARγ through a LXXXLXXXL motif. Further mechanistic studies showed that β-arrestin-1 promotes PPARa- but represses PPARγ-mediated transcriptional activities, suggesting a dual regulatory role of β-arrestin-1 for PPARs function in BAT adipogenesis. These findings provide potential therapy for obesity and metabolic disease.
This work was published in Scientific Reports entitled “β-arrestin-1 contributes to brown fat function and directly interacts with PPARa and PPARγ” on June 15, 2016.
The study was done in collaboration with Tongji University and Shanghai East Hospital.
The work was funded by the grants from the Science and Technology Commission of Shanghai Municipality and the National Natural Science Foundation of China.
AUTHOR CONTACT:
PEI Gang
Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences,
Shanghai 200031, P. R. China.
Phone: 86-21-54921371
E-mail: gpei@sibs.ac.cn
KEYWORDS:
Brown adipose tissue, β-arrestin-1, PPARa, PPARγ
NEWS ABSTRACT:
Recently, novel roles of β-arrestin-1 in brown adipose tissue have been found by Chinese researchers. A recent work by Prof. PEI Gang’s lab at Institute of Biochemistry and Cell Biology (SIBCB), Shanghai Institutes for Biological Sciences(SIBS), Chinese Academy of Sciences (CAS) and co-workers, revealed that genetic ablation of β-arrestin-1, a scaffold protein in diverse protein complexes, led to enhanced cold tolerance and increased thermogenic gene expression. By biolayer interferometry assay, the author found that β-arrestin-1 directly interacts with PPARa and PPARγ, critical regulators in metabolism, through a LXXXLXXXL motif. Moreover, D371 in PPARa and L311/N312/D380 in PPARγ are required for their interactions with β-arrestin-1 by nuclear magnetic resonance (NMR) spectroscopy analysis. Further mechanistic studies showed that β-arrestin-1 promotes PPARa- but represses PPARγ-mediated transcriptional activities, providing potential regulatory pathway for BAT function.
Figure: Model of β-arrestin-1 and PPARα/γ in brown fat adipogenesis. Binding of β-arrestin-1 to PPARα and PPARγ dually modulates transcriptional activities of PPARα and PPARγ and regulates brown fat adipogenesis and function.
(Image by Prof. PEI Gang’s group)
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