ESPE Yearbook of Paediatric Endocrinology

Cell Rep. 2022 Jan 25;38(4):110298. doi: 10.1016/j.celrep.2022.110298Brief Summary: This study describes the cryo-EM structure of human ATP Binding Cassette Subfamily G Member 1 (ABCG1) in complex with cholesterol. The authors propose a structural mechanism whereby cholesterol is recruited from cell membranes by sphingomyelin and loaded on nascent HDL particles.ABC...

To read the full abstract: Cell Stem Cell vol. 26,2 (2020): 262–276.e4. doi: https://www.sciencedirect.com/science/article/pii/S1934590919305235?via%3DihubThis paper describes a transcriptional analysis of human spermatogonial stem cells during puberty and the involvement of testosterone in Sertoli cell maturation.The...

To read the full abstract: N Engl J Med 2017;377:633-643Proprotein convertase subtilisin/kexin type 9 (PCSK9) regulates levels of plasma LDL-C by interacting with the LDL receptor. After binding and internalization, PCSK9 directs the LDL receptor to lysosomal degradation and inhibits its recycling to the cell surface, and thus accelerates the degradation of hepatic LDL receptors. This reduces the ...

In Brief: These authors studied liver-specific SIRT2 knockout mice to examine how loss of hepatocyte SIRT2 (Sirtuin 2) prevents bone loss in aged mice. Hepatocyte SIRT2 deficiency led to upregulation of Leucine rich α2 glycoprotein (LRG1) in hepatocyte-derived small extracellular vesicles (sEVs) which inhibited osteoclastogenesis in bone marrow.Commentary: Liver-bone communication has been implicated in bone homeostasis. P...

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: The authors developed a model to estimate the worldwide prevalence of Type 1 diabetes (T1D) in 2040. Compared to 2021, when an estimated 8.4 million individuals had T1D (including 18% < 20 years), the prevalent cases are expected to increase to 13.5–17.4 million in 2040, with the largest relative increase taking place in low- and middle-income countries.This model, using published data (available from only 97 countries worldwide) ...

Brief Summary: This study examined the pulsatile secretion of TSH and its regulatory role in thyroid hormone (TH) synthesis in mice. Using a novel ultra-sensitive ELISA for mouse TSH, it shows that TSH pulsatility plays a critical role in regulating thyroid function.In addition to mapping the normal TSH secretion pattern in healthy mice, and the secretion pattern in a mouse model of disease (mouse made hypothyroid by an iodine-deficient diet enriched wit...

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...

To read the full abstract: Science 2019;365:386–392.By genetically engineering mice, the authors deleted the enzyme dihydroceramide desaturase 1 (DES1), which normally inserts a conserved double bond into the backbone of ceramides. Ablation of DES1 from whole animals or tissue-specific deletion in the liver and/or adipose tissue resolved hepatic steatosis and insulin resistance in mice caused by leptin deficiency or obesogenic diets<p c...

To read the full abstract: Nature 2017;550:255-259Loss of appetite, and even aversion to food, is a common experience during periods of illness (e.g. infection and pyrexia) and/or treatment (e.g. chemotherapy). This responses is distinct from the body’s homeostatic mechanisms (the hypothalamic leptin receptor-AGRP-POMC-MC4R axis), which normally regulate appetite and weight gain in ch...