25 research outputs found

    SIRT6 Promotes Hepatic Beta-Oxidation via Activation of PPARα

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    The pro-longevity enzyme SIRT6 regulates various metabolic pathways. Gene expression analyses in SIRT6 heterozygotic mice identify significant decreases in PPARα signaling, known to regulate multiple metabolic pathways. SIRT6 binds PPARα and its response element within promoter regions and activates gene transcription. Sirt6+/− results in significantly reduced PPARα-induced β-oxidation and its metabolites and reduced alanine and lactate levels, while inducing pyruvate oxidation. Reciprocally, starved SIRT6 transgenic mice show increased pyruvate, acetylcarnitine, and glycerol levels and significantly induce β-oxidation genes in a PPARα-dependent manner. Furthermore, SIRT6 mediates PPARα inhibition of SREBP-dependent cholesterol and triglyceride synthesis. Mechanistically, SIRT6 binds PPARα coactivator NCOA2 and decreases liver NCOA2 K780 acetylation, which stimulates its activation of PPARα in a SIRT6-dependent manner. These coordinated SIRT6 activities lead to regulation of whole-body respiratory exchange ratio and liver fat content, revealing the interactions whereby SIRT6 synchronizes various metabolic pathways, and suggest a mechanism by which SIRT6 maintains healthy liver

    Pedunculated hepatic focal nodular hyperplasia

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    Potassium Level Variation Following Packed Cell Transfusion in Critically Ill Adult Patients—How Alert Should We Be?

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    One of the most clinically important effects following the administration of packed cell transfusion (PCT) is hyperkalemia, which can cause severe life-threatening cardiac arrhythmias. This retrospective population-based cohort study included adults hospitalized between January 2007 and December 2019 in a general intensive care unit for 24 h or more, with normal levels of serum potassium on admission. We assessed changes in serum potassium levels after administration of one unit of packed cells and sought to identify clinical parameters that may affect these changes. We applied adjusted linear mixed models to assess changes in serum potassium. The mean increase in serum potassium was 0.09 mEq/L (C.U 0.04–0.14, p-value < 0.001) among the 366 patients who were treated with a single PCT compared to those not treated with PCT. Increased serum potassium levels were also found in patients who required mechanical ventilation, and to a lesser degree in those treated with vasopressors. Hypertension, the occurrence of a cerebrovascular accident, and increased creatinine levels were all associated with reduced serum potassium levels. Due to the small rise in serum potassium levels following PCT, we do not suggest any particular follow-up measures for critically ill patients who receive PCT
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