ESPE Yearbook of Paediatric Endocrinology

Brief summary: Villanueva-Carmona et al. identified succinate as a mediating metabolite in leptin secretion. Its action is mediated by the succinate receptor SUCNR in adipocytes via the circadian clock in an AMPK/JNK-C/EBPa-dependent manner.Although the regulatory circuits of leptin action on hunger and satiety are well understood, the pathways that mediate acute leptin production in the adipose tissue are less investigated. To investigate how a...

Brief summary: This collaborative study identified 13 monoallelic rare loss-of-function (LoF) variants in the serotonin 2C receptor (HTR2C) gene in 19 unrelated individuals with hyperphagia, severe early-onset obesity, and some degree of maladaptive behaviour. The authors used exome sequencing in 2548 individuals with severe obesity and 1117 control individuals without obesity. They found that HTR2C variants cause monogenic obesity by demonstrating t...

Brief summary: In this double-blind, randomized, placebo-controlled trial, bempedoic acid (Nexletol) reduced the incidence of a composite cardiovascular.Comment: Bempedoic acid is an ATP citrate lyase inhibitor. ATP citrate lyase catalyses the conversion of citrate to acetyl-CoA, the fundamental substrate required for the synthesis of cholesterol and fatty acids. By inhibiting the cholesterol synthesis pathway, bempedoic acid reduces intra-hepatic LDL-C....

Brief Summary: This study provides evidence for the role of miR-137/325 in obesity-induced hypogonadism (OIH) and metabolic dysfunction.Obesity is associated with different forms of gonadal and reproductive dysfunction, including central male hypogonadism (1, 2). Although weight loss is the ideal therapeutic strategy for patients with OIH, significant weight loss is usually difficult to achieve only with lifestyle changes. Hence, androgen administration ...

Brief Summary: This single-centre retrospective cohort study offers valuable insights into the trajectory of weight gain in a paediatric craniopharyngioma cohort over a mean follow-up period of 10.4 years, reinforcing the necessity for targeted interventions to address this issue.Craniopharyngioma poses a substantial clinical challenge in paediatric patients, primarily due to the risk of hypothalamic involvement. A particularly severe long-term consequen...

Brief Summary: These authors performed exhaustive saturation genome editing (SGE) of BAP1 (BRCA1-associated protein 1), the disruption of which is linked to tumorigenesis and altered neurodevelopment. 18,108 unique variants were characterized, of which 6,196 were found to have abnormal functions. These were then used to evaluate phenotypic associations in the UK Biobank. BAP1 variants were also characterized in a large population-ascertained tumor collection,...

Short summary: This study examined ex vivo the function of the sperm-specific CatSper-channel in almost 2300 men undergoing investigation for infertility. In 9 infertile men with normal semen analysis but pathologic sperm motility, biallelic variants in genes forming the CatSper-channel were found, either in CATSPER2 or CATSPERE. These men and their partners failed to conceive naturally and medically assisted reproduction (MAR) was successful only via intracytoplasmic...

Brief Summary:This study in mice and humans shows how paternal overweight at conception affects the metabolism of their offspring. Sperm-borne mt-sncRNAs (mitochondrial encoded or derived small non-coding RNAs) are altered by a 2-week high fat diet (HFD) challenge in mice, likely through specific upregulation of mt-tsRNAs (mitochondrial transfer RNAs) caused by mitochondrial dysfunction. In humans, mt-tsRNAs in spermatozoa correlate with body mass index. Genetically engineered...

In Brief This phase 3 trial including 966 adults with biopsy-confirmed non-alcoholic steatohepatitis (NASH) with fibrosis were randomly assigned (1:1:1 ratio) to once-daily resmetirom 80 mg or 100 mg or placebo. Resmetirom, both 80 and 100 mg daily, were superior to placebo with respect to NASH resolution and improvement in liver fibrosis.NASH resolution occurred more frequently in patients on 80-mg (25.9%) and 100-mg resmetirom (29.9%) than on placebo (...

In Brief: The authors perform a population intervention effects analysis of 33 longitudinal cohorts (total 83 671 children, 662 763 measurements), from 15 low- and middle-income counties (LMICs). They estimate that improving maternal anthropometry and child condition at birth would increase population mean length-for-age z-scores by up to 0.40 and weight-for-length z -scores by up to 0.15 by 24 months of age.This is 1 of 3 full articles publishe...