Michel van Weeghel

Metabolic dependency of malonate protection against cardiac ischemia–reperfusion injury

Qian Wang, Xin Hu, Yang Xiao, Rianne Nederlof et autres

Malonate, an inhibitor of mitochondrial succinate dehydrogenase (SDH), protects against ischemia-reperfusion injury (IRI) when given at early reperfusion, making it a promising therapeutic agent for acute myocardial infarct (AMI) and stroke patients. Prior to clinical studies, it is essential to identify potential …

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Glutamine-driven mTORC1 activity enforces glycolytic bias, hyperactivation and aberrant proliferation in T cells in chronic B-cell leukemia

Nienke B. Goedhart, Elena Camerini, Gaspard Cretenet, Anita E. Grootemaat et autres

Summary T-cell metabolic dysfunction is increasingly recognized as a hallmark of poor antitumor responses. Still, how distinct metabolic states shape T-cell function and which signaling pathways sustain them remains unclear. Here, we show that T cells from patients with chronic lymphocytic leukemia …

nl, de, us, fr, es (code pays fourni par la source)

Hepatocyte-specific Cas9-mediated editing of G6pc and Slc37a4 elicits comparable biochemical and regulatory responses between glycogen storage disease (GSD) type Ia and Ib mice

Kishore Alagere Krishnamurthy, Ruiqi Xiao, Martijn G. S. Rutten, Trijnie Bos et autres

BACKGROUND/OBJECTIVE: Glycogen storage disease type I (GSD I) is an autosomal recessive inborn error of carbohydrate metabolism. Patients with GSD type Ia and Ib exhibit overlapping and distinct symptoms and complications. Notably, GSD Ia patients show more severe hypertriglyceridemia and higher risk …

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Mitochondrial carrier SLC25A34 links clock, diet, and temperature control of interorganellar lipid cycling

Юлия Караваева, Astrid Linde Basse, Samuel A.J. Trammell, Mohammed Faiz Hussain et autres

Abstract Adipocyte lipid metabolism is coordinated by circadian rhythms, diet, and environmental temperature. Yet how these diverse signals are molecularly integrated remains unknown. Here we show that clock, diet, and temperature cues converge on the orphan mitochondrial transporter, SLC25A34, to orchestrate thermogenic …

dk, ca, us, de, nl, gb, at (code pays fourni par la source)

Changes in cardiac myosin acetylation disrupt the super-relaxed state in genotype-negative hypertrophic cardiomyopathy with type 2 diabetes

E E Nollet, Chahida Chaami, Helena Bogdanovic Keleman, Elise Gerlach Melhedegaard et autres

BACKGROUND: Patients with hypertrophic cardiomyopathy (HCM) and type 2 diabetes (T2D) have a more severe cardiac phenotype and worse clinical course than non‑diabetic patients. To identify how T2D aggravates the disease and whether the most abundant cardiac protein, myosin, is involved, we …

dk, nl, us, gb, cn (code pays fourni par la source)

Human whole-blood NAD+ levels do not vary with age or lifestyle interventions

Maria M. Trętowicz, Angelique M. L. Scantlebery, Bauke V. Schomakers, Kaan D. Eroğlu et autres

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The early metabolic cardiac targets of empagliflozin during the development of heart failure, independent of SGLT2 inhibition

Sha Chen, Xin Hu, Qian Wang, Diane Bakker et autres

Background & purpose Cardiac metabolic changes are known early drivers of heart failure (HF). Recent preclinical research showed that protection against HF by sodium glucose transporter 2 inhibitors (SGLT2i) is independent of SGLT2 inhibition. Here, we unravel the SGLT2-independent metabolic effects of …

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Targeting phospholipase Pla2g15 reduces long-chain BMP phospholipids abundance and senescence in kidney cells

Sanne van der Rijt, Simone W. Denis, Loes M. Butter, Bauke V. Schomakers et autres

Chronic kidney disease (CKD), a major age-related pathology, is driven by the accumulation of chronic senescent proximal tubular epithelial cells (TECs), promoting fibrosis and functional decline.Although senescence involves metabolic reprogramming, the role of complex lipid metabolism in TECs senescence remains poorly understood.Here, …

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Nicotinamide riboside prevents mitochondrial dysfunction in nemaline myopathy type 6

R. Baelde, Leander A. Vonk, Edgar E. Nollet, Ricardo Andres Galli et autres

Nemaline Myopathy type 6 (NEM6) is a congenital myopathy caused by variants in Kelch-repeat-and-BTB-(POZ)-Domain-Containing-13 (KBTBD13). The majority of the NEM6 patients harbor the Dutch founding variant KBTBD13R408C (c.1222C > T, p.Arg408Cys) and experience skeletal muscle weakness and sarcomere-based hypercontractility. Histological characterization of …

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