Emilie Montastier

Context: Hyperphagia, overweight, and obesity are frequent in people with rare neurodevelopmental disorders (NDDs). Prader-Willi syndrome (PWS) is a rare NDD with hyperphagia and hyperghrelinemia. Objectives: To measure ghrelin levels, hyperphagia and caregiver burden in rare NDDs patients to understand pathophysiology and improve care. Design: A single-visit, noninterventional, national, multicenter, cross-sectional study. Setting: Seven French reference centers for rare NDDs participated. Patients: A total of 130 patients (43% children) with a rare genetic NDD (27 distinct conditions) were included. Their median age was 19.8 years. Three control groups were used for comparison: “PWS” (n = 153), “Obese” (n = 49), and “Lean” (n = 31) groups. Main outcome measure(s): The primary endpoint was ghrelin level (total, acylated, unacylated). The first secondary endpoint was hyperphagia questionnaire (HQ) scores. Results: Median total ghrelin levels were 76.7 (22.2-1110.9) pg/mL; median acylated levels were 33.7 (8.0-754.3) pg/mL; and median unacylated levels were 44.2 (11.5-356.6) pg/mL, which were lower than the PWS group (P < .001) and no different from the Obese group. The mean HQ total score was 26.3 (10-46) for children and 24.0 (11-52) for adults. The HQ total score was statistically higher in children with NDDs and lower in adults compared to PWS. The mean Zarit Burden Interview score was 37.8 (6-74) in children and 37.6 (2-76) in adults, and was positively correlated with the HQ total score. Conclusion: Ghrelin levels were normal in our study population. Hyperghrelinemia is a biomarker of PWS. Hyperphagia is more prevalent and severe in children with NDDs compared with PWS.

Type 2 diabetes (T2D) and obesity are strongly associated with low natriuretic peptide (NP) plasma levels and a down-regulation of NP guanylyl cyclase receptor-A (GCA) in skeletal muscle and adipose tissue. However, no study has so far provided evidence for a causal link between atrial NP (ANP)/GCA deficiency and T2D pathogenesis. Here, we show that both systemic and skeletal muscle ANP/GCA deficiencies in mice promote metabolic disturbances and prediabetes. Skeletal muscle insulin resistance is further associated with altered mitochondrial function and impaired endurance running capacity. ANP/GCA-deficient mice exhibit increased proton leak and reduced content of mitochondrial oxidative phosphorylation proteins. We further show that GCA is related to several metabolic traits in T2D and positively correlates with markers of oxidative capacity in human skeletal muscle. Together, these results indicate that ANP/GCA signaling controls muscle mitochondrial integrity and oxidative capacity in vivo and plays a causal role in the development of prediabetes.

The 5/6 nephrectomy and adenine-induced nephropathy mouse models have been extensively used to study Chronic Kidney Disease (CKD)-related cachexia. One common caveat of these CKD models is the cross-sectional nature of comparisons made versus controls. We here performed a comprehensive longitudinal assessment of body composition and energy metabolism in both models. The most striking finding is that weight loss is largely driven by reduced food intake which promotes rapid loss of lean and fat mass. However, in both models, mice catch up weight and lean mass a few days after the surgery or when they are switched back to standard chow diet. Muscle force and mass are fully recovered and no sign of cachexia is observed. Our data demonstrate that the time-course of kidney failure and weight loss are unrelated in these common CKD models. These data highlight the need to reconsider the relative contribution of direct and indirect mechanisms to muscle wasting observed in CKD.

The European hidradenitis suppurativa (HS) guidelines recommend a multidisciplinary approach for patients with HS and management of comorbidities. We aimed to describe the organization of a multidisciplinary HS program and characterize the patient population. We conducted a retrospective study of patients with HS undergoing prospectively defined multidisciplinary work-up including examinations by a dermatologist, plastic surgeon, smoking specialist, and nutritionist in our outpatient unit between October 2015 and January 2017. The study included 49 patients with a sex ratio of 1:1. A total of 73.4% of patients were smokers, 20.4% were overweight, 48.9% were obese, and 30.6% had symptoms of depression. The mean Sartorius score was 30.4 (±17.6). The outcome of plastic surgery consultation was as follows: 16 patients had operations, 5 were excluded based on medical history, 9 refused surgery, and 16 remained undecided. The refusal rates for consulting with the smoking cessation and nutrition specialists were 55.8% and 69.5%, respectively. Twelve patients received antibiotics, 9 received biologics, 9 underwent medico-surgical treatment, 9 underwent surgery, and 10 were lost to follow-up. The mean visual analogue scale score for satisfaction was 8.3 (±1.6; n = 28). An integrated multidisciplinary care model for HS is associated with high patient satisfaction. Adherence to the proposed comorbidity management was higher in female patients and related to empathetic interactions with physicians.

We hypothesized that skeletal muscle contraction produces a cellular stress signal, triggering adipose tissue lipolysis to sustain fuel availability during exercise. The present study aimed at identifying exercise-regulated myokines, also known as exerkines, able to promote lipolysis. Human primary myotubes from lean healthy volunteers were submitted to electrical pulse stimulation (EPS) to mimic either acute intense or chronic moderate exercise. Conditioned media (CM) experiments with human adipocytes were performed. CM and human plasma samples were analyzed using unbiased proteomic screening and/or ELISA. Real-time qPCR was performed in cultured myotubes and muscle biopsy samples. CM from both acute intense and chronic moderate exercise increased basal lipolysis in human adipocytes. Growth and differentiation factor 15 (GDF15) gene expression and secretion increased rapidly upon skeletal muscle contraction. GDF15 protein was upregulated in CM from both acute and chronic exercise–stimulated myotubes. We further showed that physiological concentrations of recombinant GDF15 protein increased lipolysis in human adipose tissue, while blocking GDF15 with a neutralizing antibody abrogated EPS CM-mediated lipolysis. We herein provide the first evidence to our knowledge that GDF15 is a potentially novel exerkine produced by skeletal muscle contraction and able to target human adipose tissue to promote lipolysis.

We report the case of a woman with myotonic dystrophy type 1, followed for 8 years after a Roux-en-Y gastric bypass. Weigh loss was substantial (53% of initial body weight) with functional improvement in spite of the natural course of the pathology. Five other cases have been published and have reported a relatively positive benefit/risk ratio. Precautions are to be taken at the time of anesthesia and follow-up in order to detect possible degradation of muscle function.

This brief communication suggests that in patients who had bariatric surgery and in whom protein intake is lower than 60 g/d, the use of an application is likely to improve protein intake.