Nature Reviews Endocrinology

Biomineralization is the process by which organisms produce mineralized tissues. This crucial process makes possible the rigidity and flexibility that the skeleton needs for ambulation and protection of vital organs, and the hardness that teeth require to tear and grind food. The skeleton also serves as a source of mineral in times of short supply, and the intestines absorb and the kidneys reclaim or excrete minerals as needed. This Review focuses on physiological and pathological aspects of the hormonal regulation of biomineralization. We discuss the roles of calcium and inorganic phosphate, dietary intake of minerals and the delicate balance between activators and inhibitors of mineralization. We also highlight the importance of tight regulation of serum concentrations of calcium and phosphate, and the major regulators of biomineralization: parathyroid hormone (PTH), the vitamin D system, vitamin K, fibroblast growth factor 23 (FGF23) and phosphatase enzymes. Finally, we summarize how developmental stresses in the fetus and neonate, and in the mother during pregnancy and lactation, invoke alternative hormonal regulatory pathways to control mineral delivery, skeletal metabolism and biomineralization.

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Lipid and glucose metabolism in white adipocytes: pathways, dysfunction and therapeutics

Pauline Morigny, Jeremie Boucher, Peter Arner & Dominique Langin

doi : 10.1038/s41574-021-00471-8

Nature Reviews Endocrinology volume 17, pages276–295 (2021)

In mammals, the white adipocyte is a cell type that is specialized for storage of energy (in the form of triacylglycerols) and for energy mobilization (as fatty acids). White adipocyte metabolism confers an essential role to adipose tissue in whole-body homeostasis. Dysfunction in white adipocyte metabolism is a cardinal event in the development of insulin resistance and associated disorders. This Review focuses on our current understanding of lipid and glucose metabolic pathways in the white adipocyte. We survey recent advances in humans on the importance of adipocyte hypertrophy and on the in vivo turnover of adipocytes and stored lipids. At the molecular level, the identification of novel regulators and of the interplay between metabolic pathways explains the fine-tuning between the anabolic and catabolic fates of fatty acids and glucose in different physiological states. We also examine the metabolic alterations involved in the genesis of obesity-associated metabolic disorders, lipodystrophic states, cancers and cancer-associated cachexia. New challenges include defining the heterogeneity of white adipocytes in different anatomical locations throughout the lifespan and investigating the importance of rhythmic processes. Targeting white fat metabolism offers opportunities for improved patient stratification and a wide, yet unexploited, range of therapeutic opportunities.

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The importance of the RET gene in thyroid cancer and therapeutic implications

Domenico Salvatore, Massimo Santoro & Martin Schlumberger

doi : 10.1038/s41574-021-00470-9

Nature Reviews Endocrinology volume 17, pages296–306 (2021)

Since the discovery of the RET receptor tyrosine kinase in 1985, alterations of this protein have been found in diverse thyroid cancer subtypes. RET gene rearrangements are observed in papillary thyroid carcinoma, which result in RET fusion products. By contrast, single amino acid substitutions and small insertions and/or deletions are typical of hereditary and sporadic medullary thyroid carcinoma. RET rearrangements and mutations of extracellular cysteines facilitate dimerization and kinase activation, whereas mutations in the RET kinase coding domain drive dimerization-independent kinase activation. Thus, RET kinase inhibition is an attractive therapeutic target in patients with RET alterations. This approach was initially achieved using multikinase inhibitors, which affect multiple deregulated pathways that include RET kinase. In clinical practice, use of multikinase inhibitors in patients with advanced thyroid cancer resulted in therapeutic efficacy, which was associated with frequent and sometimes severe adverse effects. However, remarkable progress has been achieved with the identification of novel potent and selective RET kinase inhibitors for the treatment of advanced thyroid cancer. Although expanded clinical validation in future trials is needed, the sustained antitumoural activity and the improved safety profile of these novel compounds is opening a new exciting era in precision oncology for RET-driven cancers.

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High resolution 3D structures of mineralized tissues in health and disease

Steve Weiner, Emeline Raguin & Ron Shahar

doi : 10.1038/s41574-021-00479-0

Nature Reviews Endocrinology volume 17, pages307–316 (2021)

A thorough knowledge of the structures of healthy mineralized tissues, such as bone or cartilage, is key to understanding the pathological changes occurring during disease. Such knowledge enables the underlying mechanisms that are responsible for pathology to be pinpointed. One high-resolution 3D method in particular — focused ion beam-scanning electron microscopy (FIB-SEM) — has fundamentally changed our understanding of healthy vertebrate mineralized tissues. FIB-SEM can be used to study demineralized matrix, the hydrated components of tissue (including cells) using cryo-fixation and even untreated mineralized tissue. The latter requires minimal sample preparation, making it possible to study enough samples to carry out studies capable of detecting statistically significant differences — a pre-requisite for the study of pathological tissues. Here, we present an imaging and characterization strategy for tissue structures at different length scales, describe new insights obtained on healthy mineralized tissues using FIB-SEM, and suggest future research directions for both healthy and diseased mineralized tissues.

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Late dumping syndrome or postprandial reactive hypoglycaemic syndrome after bariatric surgery

Frederique Van de Velde & Bruno Lapauw

doi : 10.1038/s41574-021-00473-6

Nature Reviews Endocrinology volume 17, page317 (2021)

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Reply to: Late dumping syndrome or postprandial reactive hypoglycaemic syndrome after bariatric surgery

Emidio Scarpellini, Joris Arts, Tim Vanuytsel & Jan Tack

doi : 10.1038/s41574-021-00474-5

Nature Reviews Endocrinology volume 17, pages317–318 (2021)

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