Leucine Supplementation Improves Diastolic Function in HFpEF by HDAC4 Inhibition DOI Creative Commons
Paula Ketilly Nascimento Alves, Antje Schauer,

Antje Augstein

et al.

Cells, Journal Year: 2023, Volume and Issue: 12(21), P. 2561 - 2561

Published: Nov. 2, 2023

Heart failure with preserved ejection fraction (HFpEF) is a complex syndrome associated high morbidity and mortality rate. Leucine supplementation has been demonstrated to attenuate cardiac dysfunction in animal models of cachexia heart reduced (HFrEF). So far, no data exist on leucine function HFpEF. Thus, the current study aimed investigate effect myocardial key signaling pathways an established HFpEF rat model. Female ZSF1 rats were randomized into three groups: Control (untreated lean rats), obese HFpEF_Leu (obese receiving standard chow enriched 3% leucine). started at 20 weeks age after was confirmed rats. In all animals, assessed by echocardiography baseline throughout experiment. At 32 weeks, hemodynamics measured invasively, tissue collected for assessment mitochondrial histological molecular analyses. had already improved diastolic 4 treatment. This accompanied stiffness, as well left ventricular fibrosis hypertrophy. Cardiac respiratory without alteration content. Lastly, suppressed expression nuclear localization HDAC4 Protein kinase A activation. Our show that improves decreases remodeling processes model Beneficial effects HDAC4/TGF-β1/Collagenase downregulation indicate potential use treatment

Language: Английский

Impaired skeletal muscle regeneration in diabetes: From cellular and molecular mechanisms to novel treatments DOI Creative Commons
Ever Espino‐Gonzalez, Emilie Dalbram, Rémi Mounier

et al.

Cell Metabolism, Journal Year: 2024, Volume and Issue: 36(6), P. 1204 - 1236

Published: March 14, 2024

Diabetes represents a major public health concern with considerable impact on human life and healthcare expenditures. It is now well established that diabetes characterized by severe skeletal muscle pathology limits functional capacity quality of life. Increasing evidence indicates also one the most prevalent disorders impaired regeneration, yet underlying mechanisms therapeutic treatments remain poorly established. In this review, we describe cellular molecular alterations currently known to occur during regeneration in people animal models diabetes, including its associated comorbidities, e.g., obesity, hyperinsulinemia, insulin resistance. We role myogenic non-myogenic cell types conditions or without diabetes. Therapies for gaps our knowledge are discussed, while proposing future directions field.

Language: Английский

Citations

24
Skeletal muscle mitochondrial remodeling in heart failure: An update on mechanisms and therapeutic opportunities DOI Creative Commons
Jiayu Lv, Yumeng Li,

Shuqing Shi

et al.

Biomedicine & Pharmacotherapy, Journal Year: 2022, Volume and Issue: 155, P. 113833 - 113833

Published: Oct. 7, 2022

Patients with heart failure (HF) usually present skeletal muscle diseases of varying severity, ranging from early fatigue on exercise to sarcopenia, sarcopenic obesity or cachexia, and frailty, which are significant predictors HF prognosis. Abnormal mitochondrial metabolism has been identified as one the earliest signs injury in is associated pathological alterations muscle, manifested wasting, myocyte atrophy apoptosis, fiber type shift, impaired contractile coupling, fat infiltration. In this review, we update evidence for remodeling patients animal models, including impairments ultrastructure, oxidative metabolism, electron transport chain (ETC), phosphorylation apparatus, phosphotransfer system, quality control. We also focus molecular regulatory mechanisms upstream mitochondria, circulating factors (e.g., RAAS, TNF-α IL-6, IGF-1, GH, ghrelin, adiponectin, NO) signals within myocytes PGC-1α, PPARs, AMPK, SIRT1/3, ROS, MuRF1). Besides therapies targeting signaling pathways mentioned above, such AdipoRon elamipretide, further summarize other potential pharmacological approaches like inhibitors sodium-glucose cotransporter 2 (SGLT2) dipeptidyl peptidase-4 (DPP-4), well some natural products, may have beneficial effects improving function HF. Targeting biogenesis, phosphorylation, reduction stress promising future opportunities prevention management myopathy

Language: Английский

Citations

46
Targeting MuRF1 by small molecules in a HFpEF rat model improves myocardial diastolic function and skeletal muscle contractility DOI
Volker Adams, Antje Schauer,

Antje Augstein

et al.

Journal of Cachexia Sarcopenia and Muscle, Journal Year: 2022, Volume and Issue: 13(3), P. 1565 - 1581

Published: March 17, 2022

Language: Английский

Citations

41
Ubiquitin-proteasome pathway in skeletal muscle atrophy DOI Creative Commons
Xiangsheng Pang, Peng Zhang, Xiaoping Chen

et al.

Frontiers in Physiology, Journal Year: 2023, Volume and Issue: 14

Published: Nov. 17, 2023

Skeletal muscles underpin myriad human activities, maintaining an intricate balance between protein synthesis and degradation crucial to muscle mass preservation. Historically, disruptions in this balance—where overshadows synthesis—have marked the onset of atrophy, a condition diminishing life quality and, grave instances, imperiling itself. While multiple pathways exist—including autophagy-lysosome, calcium-dependent calpain, cysteine aspartate protease systems—the ubiquitin-proteasome pathway emerges as especially cardinal avenue for intracellular degradation, wielding pronounced influence over atrophy trajectory. This paper ventures panoramic view predominant types, accentuating pathway’s role therein. Furthermore, by drawing from recent scholarly advancements, we draw associations specific pathological conditions linked atrophy. Our exploration seeks shed light on significance skeletal dynamics, aiming pave way innovative therapeutic strategies against affiliated disorders.

Language: Английский

Citations

29
Autophagy protects mitochondrial health in heart failure DOI

Yating Tang,

Wenlong Xu,

Yu Liu

et al.

Heart Failure Reviews, Journal Year: 2023, Volume and Issue: 29(1), P. 113 - 123

Published: Oct. 12, 2023

Language: Английский

Citations

17
Post‐translational modifications in diabetic cardiomyopathy DOI Creative Commons
Zhi Li, Jie Chen, Hailong Huang

et al.

Journal of Cellular and Molecular Medicine, Journal Year: 2024, Volume and Issue: 28(7)

Published: March 17, 2024

The increasing attention towards diabetic cardiomyopathy as a distinctive complication of diabetes mellitus has highlighted the need for standardized diagnostic criteria and targeted treatment approaches in clinical practice. Ongoing research is gradually unravelling pathogenesis cardiomyopathy, with particular emphasis on investigating various post-translational modifications. These modifications dynamically regulate protein function response to changes internal external environment, their disturbance homeostasis holds significant relevance development chronic ailments. This review provides comprehensive overview common involved initiation progression including O-GlcNAcylation, phosphorylation, methylation, acetylation ubiquitination. Additionally, discusses drug strategies targeting key modification targets, such agonists, inhibitors PROTAC (proteolysis chimaera) technology that targets E3 ubiquitin ligases.

Language: Английский

Citations

5
The Aging Heart in Focus: The Advanced Understanding of Heart Failure with Preserved Ejection Fraction DOI

Zhe-Wei Zhang,

Yibin Wang, Xiangqi Chen

et al.

Ageing Research Reviews, Journal Year: 2024, Volume and Issue: 101, P. 102542 - 102542

Published: Oct. 12, 2024

Language: Английский

Citations

5
Empagliflozin Preserves Skeletal Muscle Function in a HFpEF Rat Model DOI Open Access
Ephraim B. Winzer, Antje Schauer,

Erik Langner

et al.

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(19), P. 10989 - 10989

Published: Sept. 20, 2022

Besides structural alterations in the myocardium, heart failure with preserved ejection fraction (HFpEF) is also associated molecular and physiological of peripheral skeletal muscles (SKM) contributing to exercise intolerance often seen HFpEF patients. Recently, use Sodium-Glucose-Transporter 2 inhibitors (SGLT2i) clinical studies provided evidence for a significant reduction combined risk cardiovascular death or hospitalization HFpEF. The present study aimed further elucidate impact Empagliflozin (Empa) on: (1) SKM function metabolism (2) mitochondrial an established rat model. At age 24 weeks, obese ZSF1 rats were randomized either receiving standard care Empa drinking water. lean animals served as healthy controls. After 8 weeks treatment, echocardiography contractility performed. Mitochondrial was assessed saponin skinned fibers tissue snap frozen analyses. evident when compared lean—increased E/é left ventricular fraction. treatment significantly improved resulted reduced intramuscular lipid content. Better (mainly complex IV) only minor modulation atrophy-related proteins after treatment. results clearly documented beneficial effect on These effects accompanied by positive possibly modulating function.

Language: Английский

Citations

22
Targeting E3 ubiquitin ligases and their adaptors as a therapeutic strategy for metabolic diseases DOI Creative Commons

Yelin Jeong,

Ah‐Reum Oh, Young Hoon Jung

et al.

Experimental & Molecular Medicine, Journal Year: 2023, Volume and Issue: 55(10), P. 2097 - 2104

Published: Oct. 2, 2023

Abstract Posttranslational modification of proteins via ubiquitination determines their activation, translocation, dysregulation, or degradation. This process targets a large number cellular proteins, affecting all biological pathways involved in the cell cycle, development, growth, and differentiation. Thus, aberrant regulation is likely associated with several diseases, including various types metabolic diseases. Among ubiquitin enzymes, E3 ligases are regarded as most influential enzymes due to ability selectively bind recruit target substrates for ubiquitination. Continued research on regulatory mechanisms adaptors diseases will further stimulate discovery new accelerate development therapeutic options In this review, based recent discoveries, we summarize insights into roles pathogenesis by highlighting evidence obtained both human animal model studies.

Language: Английский

Citations

13
Emerging Mechanisms of Skeletal Muscle Homeostasis and Cachexia: The SUMO Perspective DOI Creative Commons
Bushra Khan,

Luis Vincens Gand,

Mamta Amrute‐Nayak

et al.

Cells, Journal Year: 2023, Volume and Issue: 12(4), P. 644 - 644

Published: Feb. 17, 2023

Mobility is an intrinsic feature of the animal kingdom that stimulates evolutionary processes and determines biological success animals. Skeletal muscle primary driver voluntary movements. Besides, skeletal muscles have immense impact on regulating glucose, amino acid, lipid homeostasis. Muscle atrophy/wasting conditions are accompanied by a drastic effect function disrupt steady-state physiology. Cachexia complex multifactorial wasting syndrome characterized extreme loss mass, resulting in dramatic decrease life quality reported mortality more than 30% patients with advanced cancers. The lack directed treatments to prevent or relieve indicates our inadequate knowledge molecular mechanisms involved cell organization etiology cancer-induced cachexia (CIC). This review highlights latest regulatory maintaining their deregulation syndromes, particularly cachexia. Recently, protein posttranslational modification small ubiquitin-like modifier (SUMO) has emerged as key mechanism implications for different aspects physiology diseases. We also atypical association SUMO-mediated pathways this context deliberate potential treatment strategies alleviate atrophy.

Language: Английский

Citations

11