Striking Cardioprotective Effects of an Adiponectin Receptor Agonist in an Aged Mouse Model of Duchenne Muscular Dystrophy.

Adiponectin (ApN) is a hormone with potent effects on various tissues. We previously demonstrated its ability to counteract Duchenne muscular dystrophy (DMD), a severe muscle disorder. However, its therapeutic use is limited.

Challenging Sarcopenia: Exploring AdipoRon in Aging Skeletal Muscle as a Healthspan-Extending Shield.

Sarcopenia, characterized by loss of muscle mass, quality, and function, poses significant risks in aging. We previously demonstrated that long-term treatment with AdipoRon (AR), an adiponectin receptor agonist, alleviated myosteatosis and muscle degeneration in middle-aged obese mice. This study aimed to determine if a shorter AR treatment could effectively offset sarcopenia in older mice.

Administration of adiponectin receptor agonist AdipoRon relieves cancer cachexia by mitigating inflammation in tumour-bearing mice.

Background: Cancer cachexia is a life-threatening, inflammation-driven wasting syndrome that remains untreatable. Adiponectin, the most abundant adipokine, plays an important role in several metabolic processes as well as in inflammation modulation. Our aim was to test whether administration of AdipoRon (AR), a synthetic agonist of the adiponectin receptors, prevents the development of cancer cachexia and its related muscle atrophy.

The Adiponectin Receptor Agonist, ALY688: A Promising Therapeutic for Fibrosis in the Dystrophic Muscle.

Duchenne muscular dystrophy (DMD) is one of the most devastating myopathies, where severe inflammation exacerbates disease progression. Previously, we demonstrated that adiponectin (ApN), a hormone with powerful pleiotropic effects, can efficiently improve the dystrophic phenotype. However, its practical therapeutic application is limited.

Inhibiting the inflammasome with MCC950 counteracts muscle pyroptosis and improves Duchenne muscular dystrophy.

Background: Duchenne muscular dystrophy (DMD) is the most common inherited human myopathy. Typically, the secondary process involving severe inflammation and necrosis exacerbate disease progression. Previously, we reported that the NLRP3 inflammasome complex plays a crucial role in this disorder.

Histological Methods to Assess Skeletal Muscle Degeneration and Regeneration in Duchenne Muscular Dystrophy.

Duchenne muscular dystrophy (DMD) is a progressive disease caused by the loss of function of the protein dystrophin. This protein contributes to the stabilisation of striated cells during contraction, as it anchors the cytoskeleton with components of the extracellular matrix through the dystrophin-associated protein complex (DAPC). Moreover, absence of the functional protein affects the expression and function of proteins within the DAPC, leading to molecular events responsible for myofibre damage, muscle weakening, disability and, eventually, premature death.

AdipoRon enhances healthspan in middle-aged obese mice: striking alleviation of myosteatosis and muscle degenerative markers.

Background: Obesity among older adults has increased tremendously. Obesity accelerates ageing and predisposes to age-related conditions and diseases, such as loss of endurance capacity, insulin resistance and features of the metabolic syndrome. Namely, ectopic lipids play a key role in the development of nonalcoholic fatty liver disease (NAFLD) and myosteatosis, two severe burdens of ageing and metabolic diseases.

Walking down Skeletal Muscle Lane: From Inflammasome to Disease.

Over the last decade, innate immune system receptors and sensors called inflammasomes have been identified to play key pathological roles in the development and progression of numerous diseases. Among them, the nucleotide-binding oligomerization domain (NOD-), leucine-rich repeat (LRR-) and pyrin domain-containing protein 3 (NLRP3) inflammasome is probably the best characterized. To date, NLRP3 has been extensively studied in the heart, where its effects and actions have been broadly documented in numerous cardiovascular diseases.

Adiponectin and Its Mimics on Skeletal Muscle: Insulin Sensitizers, Fat Burners, Exercise Mimickers, Muscling Pills … or Everything Together?

Adiponectin (ApN) is a hormone abundantly secreted by adipocytes and it is known to be tightly linked to the metabolic syndrome. It promotes insulin-sensitizing, fat-burning, and anti-atherosclerotic actions, thereby effectively counteracting several metabolic disorders, including type 2 diabetes, obesity, and cardiovascular diseases. ApN is also known today to possess powerful anti-inflammatory/oxidative and pro-myogenic effects on skeletal muscles exposed to acute or chronic inflammation and injury, mainly through AdipoR1 (ApN specific muscle receptor) and AMP-activated protein kinase (AMPK) pathway, but also via T-cadherin.

AdipoRon, a new therapeutic prospect for Duchenne muscular dystrophy.

Background: Adiponectin (ApN) is a hormone known to exhibit insulin-sensitizing, fat-burning, and anti-inflammatory properties in several tissues, including the skeletal muscle. Duchenne muscular dystrophy (DMD) is a devastating disease characterized by dystrophin deficiency with subsequent chronic inflammation, myofiber necrosis, and impaired regeneration. Previously, we showed that transgenic up-regulation of ApN could significantly attenuate the dystrophic phenotype in mdx mice (model of DMD).

Metallothionein 1 negatively regulates glucose-stimulated insulin secretion and is differentially expressed in conditions of beta cell compensation and failure in mice and humans.

Aims/hypothesis: The mechanisms responsible for beta cell compensation in obesity and for beta cell failure in type 2 diabetes are poorly defined. The mRNA levels of several metallothionein (MT) genes are upregulated in islets from individuals with type 2 diabetes, but their role in beta cells is not clear. Here we examined: (1) the temporal changes of islet Mt1 and Mt2 gene expression in mouse models of beta cell compensation and failure; and (2) the role of Mt1 and Mt2 in beta cell function and glucose homeostasis in mice.

Downregulation of the NLRP3 inflammasome by adiponectin rescues Duchenne muscular dystrophy.

Background: The hormone adiponectin (ApN) exerts powerful anti-inflammatory effects on skeletal muscle and can reverse devastating myopathies, like Duchenne muscular dystrophy (DMD), where inflammation exacerbates disease progression. The NLRP3 inflammasome plays a key role in the inflammation process, and its aberrant activation leads to several inflammatory or immune diseases. Here we investigated the expression of the NLRP inflammasome in skeletal muscle and its contribution to DMD.

Potential Therapeutic Action of Adiponectin in Duchenne Muscular Dystrophy.

Adiponectin (ApN) is a hormone that exhibits anti-inflammatory effects on skeletal muscle exposed to acute and chronic inflammation. We have previously tested the implication of ApN in Duchenne muscular dystrophy (DMD) using mdx mice, a model of DMD, and by generating transgenic mdx mice overexpressing ApN. We showed that ApN can act as a preventive agent and delay disease progression by reducing muscle inflammation/injury and improving force/myogenesis.

New targets to alleviate skeletal muscle inflammation: role of microRNAs regulated by adiponectin.

Muscle inflammation worsens metabolic disorders as well as devastating myopathies. The hormone adiponectin (ApN) has emerged has a master regulator of inflammation/immunity in several tissues including the skeletal muscle. In this work, we explore whether microRNAs regulated by ApN may represent novel mechanisms for controlling muscle inflammation.

Involvement of adiponectin in the pathogenesis of dystrophinopathy.

Background: The hormone adiponectin (ApN) is decreased in the metabolic syndrome, where it plays a key pathogenic role. ApN also exerts some anti-inflammatory effects on skeletal muscles in mice exposed to acute or chronic inflammation. Here, we investigate whether ApN could be sufficiently potent to counteract a severe degenerative muscle disease, with an inflammatory component such as Duchenne muscular dystrophy (DMD).

Adiponectin and skeletal muscle: pathophysiological implications in metabolic stress.

Upregulation of muscular adiponectin could act as a local protective mechanism to counteract cellular damage in obesity by weakening inflammation, oxidative stress, and apoptosis. To test this hypothesis, adiponectin-knockout (KO) and wild-type (WT) mice were fed a Western diet (WD). WT mice under WD conditions displayed 63% higher adiponectin expression in myocytes than those under standard laboratory diet (SLD) conditions (P = 0.

NF-κB regulates protein quality control after heat stress through modulation of the BAG3-HspB8 complex.

We previously found that the NF-κB transcription factor is activated during the recovery period after heat shock; moreover, we demonstrated that NF-κB is essential for cell survival after heat shock by activating autophagy, a mechanism that probably helps the cell to cope with hyperthermic stress through clearance of damaged proteins. In this study, we analyze the involvement of NF-κB in basal and heat-stress-induced protein quality control, by comparing the level of multiubiquitylated and/or aggregated proteins, and proteasome and autophagic activity in NF-κB-competent and NF-κB-incompetent cells. We show that NF-κB has only a minor role in basal protein quality control, where it modulates autophagosome maturation.