Reviews & Analysis

This article reviews advances in incretin-based pharmacotherapy, including the latest glucagon-like peptide 1 (GLP1) receptor agonists (GLP1RAs), ‘GLP1 plus’ agents, which combine the benefits of these agonists with the activity of additional hormones, and oral GLP1RAs, which promise to extend the benefits of GLP1 therapy.

This Review summarizes cellular processes and regulation of protein tyrosine phosphatase 1B (PTP1B), discussing evidence from in vivo preclinical and human studies. PTP1B inhibitors, which are being developed for type 2 diabetes mellitus, obesity, rare diseases (such as Rett syndrome) and some cancers, are also discussed.

The acid-labile subunit (ALS) of the insulin-like growth factor (IGF) binding protein complex regulates the endocrine transport and bioavailability of IGF-1 and IGF-2 and therefore influences postnatal growth and metabolism. This Review addresses the endocrine physiology and pathology of ALS, discusses the emerging cellular roles for ALS and outlines its involvement in disease states.

The skeleton is a metabolically active organ, with bone formation and maintenance relying on highly anabolic, nutrient-consuming processes. Here, the authors describe the current understanding of fuel selection and intermediary metabolic pathways in bone cells during bone formation and discuss how metabolic dysfunction can contribute to skeletal disease.

This Review discusses the effect of antibiotic-induced perturbations of the gut microbiome on host metabolic health. The authors outline factors that might influence the response to antibiotic use and highlight prebiotic strategies that could improve microbial composition and modulate microbial recovery.

This Review highlights how cryo-electron microscopy has revolutionized our understanding of G protein-coupled receptor (GPCR) functions. Specific examples are outlined that provide insights into GPCR biology and drug discovery in endocrinology and metabolism.

The current increasing rates of obesity are paralleled by a rise in the prevalence of chronic kidney disease. This Review outlines the potential mechanisms by which obesity might influence kidney function, but also presents evidence for the regulation of body weight by the kidney.

COVID-19 has been linked to an increase in thyroid dysfunction among current and past patients. This Review discusses and evaluates the evidence for COVID-19 causing thyroid dysfunction, including after COVID-19 vaccination and during long COVID.

Sarcopenic obesity is a growing clinical problem because of ageing populations and the increasing prevalence of obesity. This Review highlights the new consensus definition and diagnostic criteria for sarcopenic obesity, and provides an overview of the pathogenesis, clinical outcomes, and management of this syndrome.

Iatrogenic adrenal insufficiency (IAI) is the most common form of adrenal insufficiency in adult patients. This comprehensive Review aims to aid clinicians in identifying who is at risk of IAI, how to approach screening of at-risk populations and how to treat patients with IAI.

The protein complex mTORC1 is a key regulator of cellular metabolism in response to energy availability. This Review discusses the role of mTORC1 in regulating energy expenditure and the implications for the development and treatment of obesity.

In this Review, the emerging cellular and molecular mechanisms by which obesity impairs key aspects of immunity are discussed, including changes in the abundance of key hormones, dysregulation of adipose-tissue-derived extracellular vesicles and dysregulation of polyunsaturated fatty acid metabolism.

This Review describes a promising, bidirectional role for ghrelin in the interaction between circadian rhythms and metabolism. The authors explore how ghrelin affects outputs of circadian rhythm — including neuronal activity, circulating growth hormone levels, locomotor activity and eating behaviour — and discuss how circadian rhythms influence ghrelin expression.

This Review describes the luteal phase of natural menstrual cycles and in vitro fertilization (IVF) cycles. The authors highlight the need for luteal phase support during IVF, outlining various luteal phase support regimens, mechanisms for luteal phase deficiency and potential biomarkers of endometrial receptivity.

This Review discusses notable discoveries in pituitary stem cell function and highlights important areas for current and future research, including the use of pituitary organoids for the advancement of pituitary stem cell biology and pituitary organogenesis as well as potential therapeutic approaches.

Key papers on the role of nutrition and metabolic cues in puberty timing were published in 1963, and there have been many advances in this field in the subsequent 60 years. This Review discusses the latest advances in basic and translational sciences underlying the nutritional and metabolic control of pubertal development.

Genomic data from patients with thyroid cancer, combined with information on mutation-specific mechanisms from experimental models, is transforming the thyroid cancer research field. This Review summarizes the genetic alterations involved in follicular cell-derived thyroid cancer initiation and progression and their biological and clinical implications.

Thyroid hormones have key functions throughout the body. However, thyroid function declines with age and thyroid diseases increase in prevalence. This Review outlines our current knowledge about how thyroid function changes with age and the implications for patient care.

This Review discusses the current understanding of adipose tissue macrophages and T cells. Discussion of these cells is used as an example of how metabolic tissue niches can dictate immune cell function in unique ways that diverge from the classic understanding of leukocyte biology.

Inter-organ crosstalk is increasingly understood as an important mechanism contributing to insulin resistance and β-cell failure, the key features of type 2 diabetes mellitus. This Review discusses mediators of inter-organ crosstalk in type 2 diabetes mellitus, its pathogenesis and its related complications.