The peroxisome proliferator-activated receptor (PPAR) family of nuclear receptors is central to the pathophysiology and treatment of metabolic disease through the receptors' ability to regulate the expression of genes involved in glucose homeostasis, adipogenesis, and lipid metabolism. However, the mechanism by which PPAR is regulated remains incompletely understood. We generated a transgenic mouse strain (ZFP-TG) that overexpressed Zfp407 primarily in muscle and heart. Transcriptome analysis by RNA-Seq identified 1,300 differentially expressed genes in the muscle of ZFP-TG mice, among which PPAR target genes were significantly enriched. Among the physiologically important PPARγ target genes, Glucose transporter (Glut)-4 mRNA and protein levels were increased in heart and muscle. The increase in Glut4 and other transcriptional effects of Zfp407 overexpression together decreased body weight and lowered plasma glucose, insulin, and HOMA-IR scores relative to control littermates. When placed on high-fat diet, ZFP-TG mice remained more glucose tolerant than their wild-type counterparts. Cell-based assays demonstrated that Zfp407 synergistically increased the transcriptional activity of all PPAR subtypes, PPARα, PPARγ, and PPARδ. The increased PPAR activity was not associated with increased PPAR mRNA or protein levels, suggesting that Zfp407 posttranslationally regulates PPAR activity. Collectively, these results demonstrate that Zfp407 overexpression improved glucose homeostasis. Thus, Zfp407 represents a new drug target for treating metabolic disease.
Background:
Various cardiac complications such as cardiomyopathy and sudden cardiac death have been associated with Coronavirus disease 2019 (COVID-19) pandemic. We present a case of late pericardial effusion after resolution of takotsubo cardiomyopathy in COVID-19.
Case Report:
A 46-year-old male presented with acute hypoxic respiratory failure secondary to COVID-19 pneumonia. His left ventricular ejection fraction (LVEF) was 55% at admission. Over the next two days, his condition worsened requiring mechanical ventilation and inotropic support. A repeat echocardiogram revealed severe biventricular systolic dysfunction with basal hypercontractility and a drop in LVEF to 25%. Cardiac catheterization showed clean coronaries, elevated filling pressures, and reduced cardiac index (CI:1.44L/min/m
2
); hence cardiogenic shock secondary to viral myocarditis/takotsubo cardiomyopathy was suspected and an impella was placed. His condition improved with high-dose steroids, diuretics, and heart failure medication. He was subsequently weaned off circulatory and inotropic support and LVEF improved to 60% in four days, hence a provisional diagnosis of takotsubo cardiomyopathy was made. However, three days post-Impella removal he became tachycardic and hypotensive and a repeat echocardiogram showed moderate pericardial effusion with purulent material and Right Ventricle (RV) free wall diastolic collapse(image). He underwent emergent pericardiocentesis draining 800 ml of purulent fluid with pericardial drain placement. Pericardial fluid cultures returned negative. Thereafter, his condition significantly improved and he was discharged on hospital day 15.
Conclusion:
Symptomatic pericardial effusion can occur late in the clinical course even after other cardio-pulmonary symptoms have improved. This case highlights the importance of clinician awareness of the various cardiac complications in COVID-19 and their timely diagnosis and management.
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