Pyruvate dehydrogenase kinase 4 promotes ubiquitin-proteasome system-dependent muscle atrophy.

Background: Muscle atrophy, leading to muscular dysfunction and weakness, is an adverse outcome of sustained period of glucocorticoids usage. However, the molecular mechanism underlying this detrimental condition is currently unclear. Pyruvate dehydrogenase kinase 4 (PDK4), a central regulator of cellular energy metabolism, is highly expressed in skeletal muscle and has been implicated in the pathogenesis of several diseases.

Pyruvate dehydrogenase kinase 1 and 2 deficiency reduces high-fat diet-induced hypertrophic obesity and inhibits the differentiation of preadipocytes into mature adipocytes.

Obesity is now recognized as a disease. This study revealed a novel role for pyruvate dehydrogenase kinase (PDK) in diet-induced hypertrophic obesity. Mice with global or adipose tissue-specific PDK2 deficiency were protected against diet-induced obesity.

Therapeutic effect of dichloroacetate against atherosclerosis via hepatic FGF21 induction mediated by acute AMPK activation.

Dyslipidemia-induced atherosclerosis, which has a risk of high morbidity and mortality, can be alleviated by metabolic activation associated with mitochondrial function. The effect of dichloroacetate (DCA), a general pyruvate dehydrogenase kinase (PDK) inhibitor, on in vivo energy expenditure in ApoE mice fed a western diet (WD) has not yet been investigated. WD-fed ApoE mice developed atherosclerotic plaques and hyperlipidemia along with obesity, which were significantly ameliorated by DCA administration.

Phenylbutyrate Ameliorates High-Fat Diet-Induced Obesity via Brown Adipose Tissue Activation.

Obesity, which is characterized by an excessive accumulation of body fat, is one of the critical factors causing metabolic syndrome. Many studies have been performed to identify appropriate agents to control obesity, but toxicity remains a problem. Herein, we identified that phenylbutyrate (PBA), which has been used to treat urea cycle disorder with very low toxicity for a long time, efficiently inhibited high fat-induced body weight gain in a diet-induced obesity mouse model (DIO model).

Pyruvate Dehydrogenase Kinase Is a Metabolic Checkpoint for Polarization of Macrophages to the M1 Phenotype.

Metabolic reprogramming during macrophage polarization supports the effector functions of these cells in health and disease. Here, we demonstrate that pyruvate dehydrogenase kinase (PDK), which inhibits the pyruvate dehydrogenase-mediated conversion of cytosolic pyruvate to mitochondrial acetyl-CoA, functions as a metabolic checkpoint in M1 macrophages. Polarization was not prevented by PDK2 or PDK4 deletion but was fully prevented by the combined deletion of PDK2 and PDK4; this lack of polarization was correlated with improved mitochondrial respiration and rewiring of metabolic breaks that are characterized by increased glycolytic intermediates and reduced metabolites in the TCA cycle.

Recent advances in the pathogenesis of microvascular complications in diabetes.

Millions of people worldwide have diabetes, which is diagnosed by fasting blood glucose levels exceeding 126 mg/dL. Regardless of the type of diabetes, prolonged hyperglycemia is damaging to several organs including eyes, kidneys, nerve, and/or heart. The damages are associated with a high risk of morbidity and mortality.

Feasibility and safety of EUS-guided selective portal vein embolization with a coil and cyanoacrylate in a live porcine model.

Background And Objectives: Preoperative portal vein (PV) embolization using the percutaneous transhepatic approach has been performed in patients with hepatobiliary malignancy before extensive liver resection. The aim of this study is to evaluate the technical feasibility and initial safety of EUS-guided selective PV embolization using a coil and cyanoacrylate in a live porcine model.

Methods: EUS-guided selective intrahepatic PV embolization with a coil and cyanoacrylate was performed in 9 pigs.

Endoscopic ultrasonography-guided placement of a transhepatic portal vein stent in a live porcine model.

Background And Objectives: Percutaneous portal vein (PV) stent placement is used to manage PV occlusion or stenosis caused by malignancy. The use of endoscopic ultrasonography (EUS) has expanded to include vascular interventions. The aim of this study was to examine the technical feasibility and safety of EUS-guided transhepatic PV stent placement in a live porcine model.

Dimethylfumarate suppresses adipogenic differentiation in 3T3-L1 preadipocytes through inhibition of STAT3 activity.

The excessive accumulation of adipocytes contributes to the development of obesity and obesity-related diseases. The interactions of several transcription factors, such as C/EBPβ, PPARγ, C/EBPα, Nrf2, and STAT3, are required for adipogenic differentiation. Dimethylfumarate (DMF), an immune modulator and antioxidant, may function as an inhibitor of STAT3 and an activator of Nrf2.