Circulating myostatin as a biomarker of muscle mass and strength in individuals with cancer or obesity.

Background & Aims: Our study aims to determine whether myostatin (MSTN) is associated with muscle mass and strength in individuals with cancer or obesity, as well as with cancer cachexia (CC) or sarcopenic obesity (SO).

Methods: The ACTICA study included individuals with CC (n = 70) or without CC (NC, n = 73). The MYDIASECRET study included individuals with obesity evaluated before (T0) and 3 months (T3) after bariatric surgery (n = 62).

Unlocking liver health: Can tackling myosteatosis spark remission in metabolic dysfunction-associated steatotic liver disease?

Myosteatosis is highly prevalent in metabolic dysfunction-associated steatotic liver disease (MASLD) and could reciprocally impact liver function. Decreasing muscle fat could be indirectly hepatoprotective in MASLD. We conducted a review to identify interventions reducing myosteatosis and their impact on liver function.

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.

Tumoral acidosis promotes adipose tissue depletion by fostering adipocyte lipolysis.

Objective: Tumour progression drives profound alterations in host metabolism, such as adipose tissue depletion, an early event of cancer cachexia. As fatty acid consumption by cancer cells increases upon acidosis of the tumour microenvironment, we reasoned that fatty acids derived from distant adipose lipolysis may sustain tumour fatty acid craving, leading to the adipose tissue loss observed in cancer cachexia.

Methods: To evaluate the pro-lipolytic capacities of acid-exposed cancer cells, primary mouse adipocytes from subcutaneous and visceral adipose tissue were exposed to pH-matched conditioned medium from human and murine acid-exposed cancer cells (pH 6.

Myosteatosis: Diagnosis, pathophysiology and consequences in metabolic dysfunction-associated steatotic liver disease.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is associated with an increased risk of multisystemic complications, including muscle changes such as sarcopenia and myosteatosis that can reciprocally affect liver function. We conducted a systematic review to highlight innovative assessment tools, pathophysiological mechanisms and metabolic consequences related to myosteatosis in MASLD, based on original articles screened from PUBMED, EMBASE and COCHRANE databases. Forty-six original manuscripts (14 pre-clinical and 32 clinical studies) were included.

A Cross-sectional Real-life Study of the Prevalence, Severity, and Determinants of Metabolic Dysfunction-associated Fatty Liver Disease in Type 2 Diabetes Patients.

Background And Aims: Most data on liver assessment in type 2 diabetes mellitus (T2DM) patients are from retrospective cohorts with selection bias. We aimed at appraising the feasibility, results, and benefits of an outpatient systematic noninvasive screening for metabolic dysfunction-associated fatty liver disease (MAFLD) severity and determinants in T2DM patients.

Methods: We conducted a 50-week cross-sectional study enrolling adult T2DM outpatients from a diabetes clinic.

Identification of myokines susceptible to improve glucose homeostasis after bariatric surgery.

Importance And Objective: The identification of myokines susceptible to improve glucose homeostasis following bariatric surgery could lead to new therapeutic approaches for type 2 diabetes.

Methods: Changes in the homeostasis model assessment (HOMA) test were assessed in patients before and 3 months after bariatric surgery. Changes in myokines expression and circulating levels were assessed using real-time quantitative polymerase chain reaction (RT-qPCR) and enzyme-linked immunosorbent assay (ELISA).

EDA2R-NIK signalling promotes muscle atrophy linked to cancer cachexia.

Skeletal muscle atrophy is a hallmark of the cachexia syndrome that is associated with poor survival and reduced quality of life in patients with cancer. Muscle atrophy involves excessive protein catabolism and loss of muscle mass and strength. An effective therapy against muscle wasting is currently lacking because mechanisms driving the atrophy process remain incompletely understood.

Distalization of Standard Roux-en-Y Gastric Bypass: Indications, Technique, and Long-Term Results.

Introduction: Weight loss failure or weight regain after primary Roux-en-Y gastric bypass (RYGB) is a challenge for bariatric surgeons. Failure to achieve a body mass index (BMI) <35 kg/m after RYGB occurs in up to 40.0%.

Activin A Causes Muscle Atrophy through MEF2C-Dependent Impaired Myogenesis.

Activin A (ActA) is considered to play a major role in cancer-induced cachexia (CC). Indeed, circulating ActA levels are elevated and predict survival in patients with CC. However, the mechanisms by which ActA mediates CC development and in particular skeletal muscle (SM) atrophy in humans are not yet fully understood.

Serum metabolite profiling yields insights into health promoting effect of A. muciniphila in human volunteers with a metabolic syndrome.

Reduction of relative abundance in the gut microbiota is a widely accepted signature associated with obesity-related metabolic disorders. Using untargeted metabolomics profiling of fasting plasma, our study aimed at identifying metabolic signatures associated with beneficial properties of alive and pasteurized when administrated to a cohort of insulin-resistant individuals with metabolic syndrome. Our data highlighted either shared or specific alterations in the metabolome according to the form of administered with respect to a control group.

p21-Activated Kinase 1 Is Permissive for the Skeletal Muscle Hypertrophy Induced by Myostatin Inhibition.

Skeletal muscle, the most abundant tissue in the body, plays vital roles in locomotion and metabolism. Understanding the cellular processes that govern regulation of muscle mass and function represents an essential step in the development of therapeutic strategies for muscular disorders. Myostatin, a member of the TGF-β family, has been identified as a negative regulator of muscle development.

is a newly isolated human commensal bacterium preventing diet-induced obesity and metabolic disorders in mice.

Objective: To investigate the abundance and the prevalence of J115, a novel butyrate-producing bacterium isolated from the human gut both in the general population and in subjects with metabolic syndrome. To study the impact of this bacterium on host metabolism using diet-induced obese and diabetic mice.

Design: We analysed the presence and abundance of the bacterium in 11 984 subjects using four human cohorts (ie, Human Microbiome Project, American Gut Project, Flemish Gut Flora Project and Microbes4U).

Beneficial Effects of Are Not Associated with Major Changes in the Circulating Endocannabinoidome but Linked to Higher Mono-Palmitoyl-Glycerol Levels as New PPARα Agonists.

is considered as one of the next-generation beneficial bacteria in the context of obesity and associated metabolic disorders. Although a first proof-of-concept of its beneficial effects has been established in the context of metabolic syndrome in humans, mechanisms are not yet fully understood. This study aimed at deciphering whether the bacterium exerts its beneficial properties through the modulation of the endocannabinoidome (eCBome).

Linking the Endocannabinoidome with Specific Metabolic Parameters in an Overweight and Insulin-Resistant Population: From Multivariate Exploratory Analysis to Univariate Analysis and Construction of Predictive Models.

The global obesity epidemic continues to rise worldwide. In this context, unraveling new interconnections between biological systems involved in obesity etiology is highly relevant. Dysregulation of the endocannabinoidome (eCBome) is associated with metabolic complications in obesity.

Inflammation-induced cholestasis in cancer cachexia.

Background: Cancer cachexia is a debilitating metabolic syndrome contributing to cancer death. Organs other than the muscle may contribute to the pathogenesis of cancer cachexia. This work explores new mechanisms underlying hepatic alterations in cancer cachexia.

Marked Increased Production of Acute Phase Reactants by Skeletal Muscle during Cancer Cachexia.

Loss of skeletal muscle mass in cancer cachexia is recognized as a predictor of mortality. This study aimed to characterize the changes in the muscle secretome associated with cancer cachexia to gain a better understanding of the mechanisms involved and to identify secreted proteins which may reflect this wasting process. The changes in the muscle proteome of the C26 model were investigated by label-free proteomic analysis followed by a bioinformatic analysis in order to identify potentially secreted proteins.

Link between gut microbiota and health outcomes in inulin -treated obese patients: Lessons from the Food4Gut multicenter randomized placebo-controlled trial.

Background: The gut microbiota is altered in obesity and is strongly influenced by nutrients and xenobiotics. We have tested the impact of native inulin as prebiotic present in vegetables and added as a supplement on gut microbiota-related outcomes in obese patients. Metformin treatment was analyzed as a potential modulator of the response.

Supplementation with Akkermansia muciniphila in overweight and obese human volunteers: a proof-of-concept exploratory study.

Metabolic syndrome is characterized by a constellation of comorbidities that predispose individuals to an increased risk of developing cardiovascular pathologies as well as type 2 diabetes mellitus. The gut microbiota is a new key contributor involved in the onset of obesity-related disorders. In humans, studies have provided evidence for a negative correlation between Akkermansia muciniphila abundance and overweight, obesity, untreated type 2 diabetes mellitus or hypertension.

Twist1 Activation in Muscle Progenitor Cells Causes Muscle Loss Akin to Cancer Cachexia.

Cancer cachexia is characterized by extreme skeletal muscle loss that results in high morbidity and mortality. The incidence of cachexia varies among tumor types, being lowest in sarcomas, whereas 90% of pancreatic ductal adenocarcinoma (PDAC) patients experience severe weight loss. How these tumors trigger muscle depletion is still unfolding.

Increased gut permeability in cancer cachexia: mechanisms and clinical relevance.

Intestinal disorders often occur in cancer patients, in association with body weight loss, and this alteration is commonly attributed to the chemotherapy. Here, using a mouse model of cancer cachexia induced by ectopic transplantation of C26 cancer cells, we discovered a profound alteration in the gut functions (gut permeability, epithelial turnover, gut immunity, microbial dysbiosis) independently of any chemotherapy. These alterations occurred independently of anorexia and were driven by interleukin 6.

Biomarkers of cancer cachexia.

Cachexia is a complex multifactorial syndrome, characterized by loss of skeletal muscle and fat mass, which affects the majority of advanced cancer patients and is associated with poor prognosis. Interestingly, reversing muscle loss in animal models of cancer cachexia leads to prolong survival. Therefore, detecting cachexia and maintaining muscle mass represent a major goal in the care of cancer patients.

Circulating Activin A predicts survival in cancer patients.

Background: Several experimental evidences pinpoint the possible role of Activin A (ActA) as a driver of cancer cachexia. Supporting this hypothesis, we showed recently that human cancer cachexia is associated with high ActA levels. Moreover, ActA levels were correlated with body weight loss and skeletal muscle density, two prognostic factors in cancer patients.

A purified membrane protein from Akkermansia muciniphila or the pasteurized bacterium improves metabolism in obese and diabetic mice.

Obesity and type 2 diabetes are associated with low-grade inflammation and specific changes in gut microbiota composition. We previously demonstrated that administration of Akkermansia muciniphila to mice prevents the development of obesity and associated complications. However, the underlying mechanisms of this protective effect remain unclear.

Role of IGF-I in follistatin-induced skeletal muscle hypertrophy.

Follistatin, a physiological inhibitor of myostatin, induces a dramatic increase in skeletal muscle mass, requiring the type 1 IGF-I receptor/Akt/mTOR pathway. The aim of the present study was to investigate the role of IGF-I and insulin, two ligands of the IGF-I receptor, in the follistatin hypertrophic action on skeletal muscle. In a first step, we showed that follistatin increases muscle mass while being associated with a downregulation of muscle IGF-I expression.