SUMOylation of AMPK alpha 1 by PIAS4 specifically regulates mTORC1 signalling

AMP-activated protein kinase (AMPK) inhibits several anabolic pathways such as fatty acid and protein synthesis, and identification of AMPK substrate specificity would be useful to understand its role in particular cellular processes and develop strategies to modulate AMPK activity in a substrate-specific manner. Here we show that SUMOylation of Z attenuates AMPK activation specifically towards mTORC1 signalling. SUMOylation is also important for rapid inactivation of AMPK, to allow prompt restoration of mTORC1 signalling. PIAS4 and its SUMO E3 ligase activity are specifically required for the AMPK alpha 1 SUMOylation and the inhibition of AMPK alpha 1 activity towards mTORC1 signalling. The activity of a SUMOylation-deficient AMPK alpha 1a mutant is higher than the wild type towards mTORC1 signalling when reconstituted in AMPKa-deficient cells. PIAS4 depletion reduced growth of breast cancer cells, specifically when combined with direct AMPK activator A769662, suggesting that inhibiting AMPK alpha 1 SUMOylation can be explored to modulate AMPK activation and thereby suppress cancer cell growth.Peer reviewe

Prolonged sleep restriction induces changes in pathways involved in cholesterol metabolism and inflammatory responses

Sleep loss and insufficient sleep are risk factors for cardiometabolic diseases, but data on how insufficient sleep contributes to these diseases are scarce. These questions were addressed using two approaches: an experimental, partial sleep restriction study (14 cases and 7 control subjects) with objective verification of sleep amount, and two independent epidemiological cohorts (altogether 2739 individuals) with questions of sleep insufficiency. In both approaches, blood transcriptome and serum metabolome were analysed. Sleep loss decreased the expression of genes encoding cholesterol transporters and increased expression in pathways involved in inflammatory responses in both paradigms. Metabolomic analyses revealed lower circulating large HDL in the population cohorts among subjects reporting insufficient sleep, while circulating LDL decreased in the experimental sleep restriction study. These findings suggest that prolonged sleep deprivation modifies inflammatory and cholesterol pathways at the level of gene expression and serum lipoproteins, inducing changes toward potentially higher risk for cardiometabolic diseases.Peer reviewe

Nordisk energisamarbeid : Sterkt i dag – sterkere i morgen

27. oktober 2015 vedtok Nordisk ministerråd for næring, energi og regionalpolitikk (MR-NER) å foreta en strategisk gjennomlysning av det nordiske samarbeidet om energi og hvordan det kan utvikles de neste 5–10 årene. Den strategiske gjennomlysningen er del av Nordisk ministerråds reformprosjekt, som ble initiert av generalsekretær Dagfinn Høybråten. Det er tidligere foretatt strategiske gjennomlysninger av samarbeid om utenriks- og sikkerhetspolitikk, helse og arbeidsmarked. Mandatet var å legge fram 10–15 konkrete forslag som ytterligere kunne styrke samarbeidet på områder der betydelige positive resultater er oppnådd i løpet av de siste to tiårene. Klimakonferansen i Paris i desember 2015 og EUs ambisjoner om å arbeide fram mot en europeisk energiunion gjør denne gjennomlysningen spesielt aktuell. Den er også basert på de enkelte nordiske landenes gjennomlysning av sin nasjonale klima- og energipolitikk. Det geopolitiske landskapet er for øyeblikket i endring – global handels- og klimapolitikk er under pres, og nasjonalistiske tendenser gjør seg gjeldende i mange land. Dette byr på en rekke utfordringer for det nordiske energisamarbeidet, som har oppnådd banebrytende resultater basert på samarbeid på tvers av grensene. En rekke studier har også vist at Norden har hentet tilsvarende dramatiske velferdsmessige gevinster. Nå er tiden inne for å vurdere hvordan de nordiske landene kan bygge videre på denne suksessen til tross for ugunstige internasjonale trender. Denne gjennomlysningen har som mål å identifisere disse utfordringene, legge fram forslag til hvordan de nordiske landene kan gå videre, og inspirere til ytterligere diskusjon og debatt

Nordic Energy Co-operation : Strong today – Stronger tomorrow

On 27 October 2015, the Nordic Council of Ministers for Business, Energy and Regional Policy (MR-NER) decided to carry out a strategic review of Nordic co-operation on energy and how it could be developed over the next 5–10 years. The strategic review is part of the Nordic Council of Ministers’ reform project initiated by its Secretary General, Dagfinn Høybråten. Strategic reviews have previously been conducted on foreign and security policy, health and labour-market co-operation. The remit was to present 10–15 concrete proposals that would further enhance co-operation in areas in which significant positive outcomes have been achieved over the past two decades. The Paris Climate Change Conference of December 2015 and the EU’s goal of working towards a European Energy Union make this review particularly timely. It is also based on the Nordic countries’ own reviews of their national climate and energy policies. The geopolitical landscape is currently in a state of flux – global trade and climate policies are under pressure, and nationalist tendencies are emerging in many countries. This presents many challenges to Nordic energy co-operation, which has achieved ground-breaking results based on cross-border co-operation. Various studies have also shown that the Nordic Region has made similarly dramatic gains in terms of welfare. The time has come to assess how the Nordic countries can build on this success, despite adverse international trends. This review seeks to identify these challenges, present proposals for how the Nordic countries can move forward, and inspire further discussion and debate

Pohjoismainen energiayhteistyö : Vahva tänään – vahvempi huomenna

Elinkeino-, energia- ja aluepolitiikan ministerineuvosto (MR-NER) päätti 27. lokakuuta 2015 toteuttaa strategiaselvityksen pohjoismaisesta energiayhteistyöstä ja sen kehittämismahdollisuuksista seuraavien 5–10 vuoden aikana. Selvitys on osa pääsihteeri Dagfinn Høybråtenin käynnistämää Pohjoismaiden ministerineuvoston uudistustyötä. Tätä ennen strategiaselvityksiä on tehty ulko- ja turvallisuuspolitiikan sekä terveys- ja työelämäalan yhteistyöstä. Toimeksiantona oli esitellä 10–15 konkreettista toimintaehdotusta energiayhteistyön lisäämiseksi aloilla, joilla on saavutettu merkittäviä myönteisiä tuloksia kahden viime vuosikymmenen aikana. Pariisissa joulukuussa 2015 pidetty ilmastokokous ja EU:n energiaunionitavoite tekevät selvityksestä erityisen ajankohtaisen. Selvitys nojautuu myös Pohjoismaiden omiin selvityksiin niiden kansallisista ilmasto- ja energiapolitiikoista. Geopoliittinen tilanne on parhaillaan murroksessa, kun kansainvälinen kauppa- ja ilmastopolitiikka on ahtaalla ja monissa maissa nationalistiset suuntaukset ovat nousussa. Tämä kohdistaa monia haasteita pohjoismaiseen energiayhteistyöhön, jossa on saavutettu uraauurtavia tuloksia rajat ylittävällä yhteistyöllä. Monet tutkimukset ovat myös osoittaneet, että Pohjoismaiden hyvinvointi on lisääntynyt yhtä merkittävästi. Nyt on aika arvioida, miten Pohjoismaat voivat jatkaa menestyksen tiellä epäsuotuisista kansainvälisistä suuntauksista huolimatta. Selvitys pyrkii tunnistamaan haasteet, esittelemään ehdotuksia Pohjoismaiden tulevasta suunnasta sekä tarjoamaan virikkeitä tulevaan keskusteluun