inducible kinase 2 (SIK2) is expressed abundantly in adipose tissues and represses cAMP-response element-binding protein (CREB)-mediated gene expression by phosphorylating the coactivator transducer of regulated CREB activity (TORC2). Phosphorylation at Ser 587 of SIK2 diminishes its TORC2 phosphorylation activity. In 3T3-L1 white adipocytes, SIK2 downregulates lipogenic gene in response to nutritional stresses. To investigate the impact of SIK2 on the function of brown adipose tissue (BAT), we used T37i brown adipocytes, mice with diet-induced obesity, and SIK2 mutant (S587A) transgenic mice. When T37i adipocytes were treated with insulin, the levels of peroxisome proliferator-activated receptor-coactivator-1␣ (PGC-1␣) and uncoupling protein-1 (UCP-1) mRNA were increased, and the induction was inhibited by overexpression of SIK2 (S587A) mutant or dominant-negative CREB. Insulin enhanced SIK2 phosphorylation at Ser 587 , which was accompanied by decrease in phospho-TORC2. Similarly, the decrease in the level of SIK2 phosphorylation at Ser 587 was observed in the BAT of mice with diet-induced obesity, which was negatively correlated with TORC2 phosphorylation. To confirm the negative correlation between SIK2 phosphorylation at Ser 587 and TORC2 phosphorylation in BAT, SIK2 mutant (S587A) was overexpressed in adipose tissues by using the adipocyte fatty acid-binding protein 2 promoter. The expression of recombinant SIK2 (S587A) was restricted to BAT, and the levels of phospho-TORC2 were elevated in BAT of transgenic mice. Male transgenic mice developed high-fat diet-induced obesity, and their BAT expressed low levels of PGC-1␣
Ethnically divided societies often seek political cohesion by pursuing nationalizing policies. Latvia has had some experience of this, for example, with the notion that citizens should speak the national language and respect government institutions coincides with portrayals of ethnic minorities as a challenge to democracy. The focus on nation-state building has resulted in persistently low levels of political engagement and public confidence among the citizenry. Public survey data shows that many voters believe their concerns have been neglected by elected representatives, who have fixed their attention on ethnopolitical issues. While we see no demonstrable correlation between ethnicity and levels of political dejection, ethnonational politics explains unstable voter-representative relations and electoral volatility during the Saeima elections from 2010-2018. These unanticipated effects of nation-state building on Latvia's electoral politics invite a rethinking of the relationship between voters and their elected representatives in democratically consolidated, yet divided nations.
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