ESPE Yearbook of Paediatric Endocrinology

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...

To read the full abstract: Diabetes Care. 2017;40:1249-1255Children and adolescents who present in ketoacidosis at manifestation of the disease might represent a subgroup of patients that may have less resilience factors in their families, less adherence to medical advice, might be less attentive to medical symptoms and might be less knowledgeable of medical issues. In addition, they may carry biolog...

Mol Cell Endocrinol. 2021 May 1;527:111218. doi: 10.1016/j.mce.2021.111218. PMID: 33636254This study used a high fat and high sucrose diet to generate obese mice. The offspring of these mice showed activation of the unfolding protein response and the heat-shock response in the hypothalamus as early as weaning. This was associated with malformed paraventricular nucleus axonal projections ...

To read the full abstract: Endocrinology vol. 161,2 (2020): bqz041. doi: https://academic.oup.com/endo/article/161/2/bqz041/5698115This mouse study demonstrates the influence of maternal nutrition during lactation on offspring gut microbiota and its consequences on metabolism and puberty timing. Childhood obesity is a risk factor for the deve...

Brief Summary: IGF1R signaling in cells expressing Kiss1 gene affects energy balance, food intake, and physical activity in a sex-specific manner. Female IGF1RKiss1 mice showed lower body weight and food intake plus higher energy expenditure and physical activity. This phenotype was associated with higher proopiomelanocortin (POMC) expression. The additional deletion of insulin receptor (IR) in Kiss1-expressing cells reversed the lean phenotype seen in female IGF1R<...

Brief summary: The authors used data from the Global Burden of Disease 2019 to examine the incidence, disability adjusted life years and mortality of early onset type 2 diabetes T2D) in those 15–39 years of age. This showed that early onset T2D is a growing global health problem in adolescents and young adults, particularly in low-middle- and middle-income countries.Early onset of type 2 diabetes (T2D) is associated with longer lifetime exposure hyp...

Cell Stem Cell. 2022 Feb 3;29(2):328-343.e5. doi: 10.1016/j.stem.2021.11.009. PMID: 34879244.Brief Summary: By applying single-cell RNA sequencing (scRNA-seq) to 112,376 cells of human hypothalamus ranging from 7–20 gestational weeks (GW7–20), the authors produced a spatiotemporal transcriptome atlas of human hypothalamus development and revealed critical regulatory genes control...

Brief summary: In this experimental study, pancreas-derived mesenchymal stem cells (PMSCs) were implanted into the kidney capsule of mice with streptozotocin (STZ)-induced diabetes. PMSCs led to increased levels of IL-6 in T-helper 1 and T-helper 17 cells, which transiently activated tumor necrosis factor-alpha (TNF-α) and interferon-gamma (IFN-γ), which in turn decreased levels of interleukin-17. This was associated with exocrine pancreas regeneration and rescue of ...

Brief Summary: This study performed long-read genome sequencing (lr-GS) using PacBio HiFi on several members of a four-generation family presenting with autosomal dominant (AD) 46,XY differences of sexual development (DSD). This family had undergone a lengthy molecular diagnostic process with no conclusive results. Lr-GS offers enhanced mapping capabilities in highly repetitive, homologous, and low-complexity regions, providing better assessment of structural variations and co...

Nat Metab. 2022 Feb;4(2):284-299. https://pubmed.ncbi.nlm.nih.gov/35228745/Brief Summary: This study used three high-throughput single-cell technologies to generate a pancreatic islet cell atlas from 24 organ donors with type 1 diabetes (T1D), autoantibody positive and healthy donors. The most remarkable finding was that a subset of exocrine ductal cells appears to acquire a signature of to...