fiber-type-subcellular-specific-analysis-lipid-droplet-content

Fiber Type and Subcellular-Specific Analysis of Lipid Droplet Content in Skeletal Muscle

Skeletal muscle lipid infiltration, known as myosteatosis, increases with obesity and ageing. Myosteatosis has also recently been discovered as a negative ...

Université catholique de Louvain

Obesity in childhood is associated with an increased mortality due to cardiovascular (CV) diseases in adulthood, independent of adult weight. Recent studies in children indicate that the atherosclerosis process starts at an early age and is linked to obesity.

Determinants of early atherosclerosis in obese children and adolescents.

Evaluation of the relationship between GPR43 and adiposity in human.

Persistent inflammation exacerbates the progression of Duchenne muscular dystrophy (DMD). The hormone, adiponectin (ApN), which is decreased in the metabolic syndrome, exhibits anti-inflammatory properties on skeletal muscle and alleviates the dystrophic phenotype of mdx mice. Here, we investigate whether ApN retains its anti-inflammatory action in myotubes obtained from DMD patients. We unravel the underlying mechanisms by studying the secretome and the early events of ApN.

Skeletal muscle secretome in Duchenne muscular dystrophy: a pivotal anti-inflammatory role of adiponectin.

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. Herein, we took an opposite approach and crossed mdx mice with ApN knockout mice, to obtain mdx mice with ApN depletion. The aims were to test whether ApN deficiency could worsen the mdx phenotype and whether ApN supplementation can reverse several muscle abnormalities once the disease is settled. mdx-knockout mice exhibited lower muscle force/endurance as well as increased muscle damage when compared to regular mdx mice. Local administration of the ApN gene significantly reduced the expression of several oxidative stress/inflammatory markers and increased the expression of myogenic markers in the skeletal muscle. Finally, the presence of ApN markedly reduced the activity of NF-κB, a key player in muscle inflammation and myogenesis. ApN proves to be a powerful protector of the skeletal muscle capable of reversing the disease progression, thus making it a potential therapeutic agent for DMD.

Potential Therapeutic Action of Adiponectin in Duchenne Muscular Dystrophy.

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.

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

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). Recently, an orally active ApN receptor agonist, AdipoRon, has been identified. This synthetic small molecule has the advantage of being more easily produced and administrable than ApN. The aim of this study was to investigate the potential effects of AdipoRon on the dystrophic muscle.

AdipoRon, a new therapeutic prospect for Duchenne muscular dystrophy.

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. In this review, we will report all the beneficial and protective properties that ApN can exert, specifically on the skeletal muscle as a target tissue. We will highlight its effects and mechanisms of action, first in healthy skeletal muscle including exercised muscle, and second in diseased muscle from a variety of pathological conditions. In the end, we will go over some of AdipoRs agonists that can be easily produced and administered, and which can greatly mimic ApN. These interesting and newly identified molecules could pave the way towards future therapeutic approaches to potentially prevent or combat not only skeletal muscle disorders but also a plethora of other diseases with sterile inflammation or metabolic dysfunction.

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

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. However, little is still known about NLRP3 implications in muscle disorders affecting non-cardiac muscles. In this review, we summarize and present the current knowledge regarding the function of NLRP3 in diseased skeletal muscle, and discuss the potential therapeutic options targeting the NLRP3 inflammasome in muscle disorders.

Article	Year
Determinants of early atherosclerosis in obese children and adolescents. The Journal of clinical endocrinology and metabolism\| PubMed ID: 17519311	2007
Evaluation of the relationship between GPR43 and adiposity in human. Nutrition & metabolism\| PubMed ID: 23327542	2013
Skeletal muscle secretome in Duchenne muscular dystrophy: a pivotal anti-inflammatory role of adiponectin. Cellular and molecular life sciences : CMLS\| PubMed ID: 28188344	2017
Potential Therapeutic Action of Adiponectin in Duchenne Muscular Dystrophy. The American journal of pathology\| PubMed ID: 28463682	2017
Downregulation of the NLRP3 inflammasome by adiponectin rescues Duchenne muscular dystrophy. BMC biology\| PubMed ID: 29558930	2018
AdipoRon, a new therapeutic prospect for Duchenne muscular dystrophy. Journal of cachexia, sarcopenia and muscle\| PubMed ID: 31965757	2020
Adiponectin and Its Mimics on Skeletal Muscle: Insulin Sensitizers, Fat Burners, Exercise Mimickers, Muscling Pills … or Everything Together? International journal of molecular sciences\| PubMed ID: 32283840	2020
Walking down Skeletal Muscle Lane: From Inflammasome to Disease. Cells\| PubMed ID: 34831246	2021

Sonia M. Brichard

Biography

JoVE Journal Publications

Other Publications