http://chineseinput.net/에서 pinyin(병음)방식으로 중국어를 변환할 수 있습니다.
변환된 중국어를 복사하여 사용하시면 됩니다.
- 中文 을 입력하시려면 zhongwen을 입력하시고 space를누르시면됩니다.
- 北京 을 입력하시려면 beijing을 입력하시고 space를 누르시면 됩니다.
RISS 인기검색어
- 검색키워드
- 저자 : Montminy, Marc (검색결과 3 건)
- 무료
- 기관 내 무료
- 유료
-
cAMP-inducible coactivator CRTC3 attenuates brown adipose tissue thermogenesis
Yoon, Young-Sil,Tsai, Wen-Wei,Van de Velde, Sam,Chen, Zhijiang,Lee, Kuo-Fen,Morgan, Donald A.,Rahmouni, Kamal,Matsumura, Shigenobu,Wiater, Ezra,Song, Youngsup,Montminy, Marc National Academy of Sciences 2018 PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF Vol.115 No.23
<P>In response to cold exposure, placental mammals maintain body temperature by increasing sympathetic nerve activity in brown adipose tissue (BAT). Triggering of beta-adrenergic receptors on brown adipocytes stimulates thermogenesis via induction of the cAMP/PKA pathway. Although cAMP response element-binding protein (CREB) and its coactivators-the cAMP-regulated transcriptional coactivators (CRTCs)-mediate transcriptional effects of cAMP in most tissues, other transcription factors such as ATF2 appear critical for induction of thermogenic genes by cAMP in BAT. Brown adipocytes arise from Myf5-positive mesenchymal cells under the control of PRDM16, a coactivator that concurrently represses differentiation along the skeletal muscle lineage. Here, we show that the CREB coactivator CRTC3 is part of an inhibitory feedback pathway that antagonizes PRDM16-dependent differentiation. Mice with a knockout of CRTC3 in BAT (BKO) have increased cold tolerance and reduced adiposity, whereas mice overexpressing constitutively active CRTC3 in adipose tissue are more cold sensitive and have greater fat mass. CRTC3 reduced sympathetic nerve activity in BAT by up-regulating the expression of miR-206, a microRNA that promotes differentiation along the myogenic lineage and that we show here decreases the expression of VEGFA and neurotrophins critical for BAT innervation and vascularization. Sympathetic nerve activity to BAT was enhanced in BKO mice, leading to increases in catecholamine signaling that stimulated energy expenditure. As reexpression of miR-206 in BAT from BKO mice reversed the salutary effects of CRTC3 depletion on cold tolerance, our studies suggest that small-molecule inhibitors against this coactivator may provide therapeutic benefit to overweight individuals.</P>
-
Yoon, Young-Sil,Lee, Min-Woo,Ryu, Dongryeol,Kim, Jeong Ho,Ma, Hui,Seo, Woo-Young,Kim, Yo-Na,Kim, Su Sung,Lee, Chul Ho,Hunter, Tony,Choi, Cheol Soo,Montminy, Marc R,Koo, Seung-Hoi National Academy of Sciences 2010 PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF Vol.107 No.41
<P>Fasting promotes hepatic gluconeogenesis to maintain glucose homeostasis. The cAMP-response element binding protein (CREB)-regulated transcriptional coactivator 2 (CRTC2) is responsible for transcriptional activation of gluconeogenic genes and is critical for conveying the opposing hormonal signals of glucagon and insulin in the liver. Here, we show that suppressor of MEK null 1 (SMEK1) and SMEK2 [protein phosphatase 4 (PP4) regulatory subunits 3a and 3b, respectively] are directly involved in the regulation of hepatic glucose metabolism in mice. Expression of hepatic SMEK1/2 is up-regulated during fasting or in mouse models of insulin-resistant conditions in a Peroxisome Proliferator-Activated Receptor-gamma Coactivator 1관 (PGC-1관)-dependent manner. Overexpression of SMEK promotes elevations in plasma glucose with increased hepatic gluconeogenic gene expression, whereas depletion of the SMEK proteins reduces hyperglycemia and enhances CRTC2 phosphorylation; the effect is blunted by S171A CRTC2, which is refractory to salt-inducible kinase (SIK)-dependent inhibition. Taken together, we would propose that mammalian SMEK/PP4C proteins are involved in the regulation of hepatic glucose metabolism through dephosphorylation of CRTC2.</P>
-
TORC2 Regulates Hepatic Insulin Signaling via a Mammalian Phosphatidic Acid Phosphatase, LIPIN1
Ryu, Dongryeol,Oh, Kyoung-Jin,Jo, Hee-Yeon,Hedrick, Susan,Kim, Yo-Na,Hwang, Yu-Jin,Park, Tae-Sik,Han, Joong-Soo,Choi, Cheol Soo,Montminy, Marc,Koo, Seung-Hoi Elsevier 2009 Cell metabolism Vol.9 No.3
<P><B>Summary</B></P><P>TORC2 is a major transcriptional coactivator for hepatic glucose production. Insulin impedes gluconeogenesis by inhibiting TORC2 via SIK2-dependent phosphorylation at Ser171. Interruption of this process greatly perturbs hepatic glucose metabolism, thus promoting hyperglycemia in rodents. Here, we show that hyperactivation of TORC2 would exacerbate insulin resistance by enhancing expression of LIPIN1, a mammalian phosphatidic acid phosphatase for diacylglycerol (DAG) synthesis. Diet-induced or genetic obesity increases <I>LIPIN1</I> expression in mouse liver, and TORC2 is responsible for its transcriptional activation. While overexpression of LIPIN1 disturbs hepatic insulin signaling, knockdown of LIPIN1 ameliorates hyperglycemia and insulin resistance by reducing DAG and PKCϵ activity in <I>db/db</I> mice. Finally, TORC2-mediated insulin resistance is partially rescued by concomitant knockdown of LIPIN1, confirming the critical role of LIPIN1 in the perturbation of hepatic insulin signaling. These data propose that dysregulation of TORC2 would further exaggerate insulin resistance and promote type 2 diabetes in a LIPIN1-dependent manner.</P>
연관 검색어 추천
이 검색어로 많이 본 자료
활용도 높은 자료
