People of South Asian ancestry are more likely to develop type 2 diabetes mellitus (T2DM) at a younger age and lower BMI than people of European ancestry. The reasons for this fact are poorly understood, as the majority of genetic research on T2DM has been performed in white European populations. Now, a study in Nature Medicine has used partitioned polygenic risk scores (pPS) to uncover the genetic

Research siloes slow the translation of scientific discovery to patient care and limit progress in improving treatments for Cushing disease to incremental advances. Facilitating collaborative efforts that study the complexity of pituitary neuroendocrine tumours would advance the development of targeted treatments for patients who experience a low quality of life for years owing to this rare and understudied

Correction to: Nature Reviews Endocrinology https://doi.org/10.1038/s41574-024-01052-1, published online 13 November 2024.

Several new clinical studies provide evidence for the potential of specific intermittent and periodic fasting interventions to decrease adiposity and HbA1c in patients with obesity and/or type 2 diabetes mellitus, while also reducing drug use, adverse effects and risk factors for other diseases.

In 2024, new insights identified a cluster of leptin-targeted neurons and integrative networks that link sensory inputs (heat and food perception) with feeding centres and peripheral systems. Key findings revealed hypothalamic site-specific adaptive mechanisms, in which nutritional state-dependent remodelling of extracellular compounds and neuropeptide transmission calibrate appetite via the arcuate

Established antiresorptive treatments for osteoporosis only slow down bone loss, and available osteoanabolic therapies — although more effective — have broad limitations. Recent insights into sex-specific systemic regulation of skeletal mass, an enhanced understanding of the cellular complexity of bone marrow and innovative options such as senolytics have fuelled the development of potentially transformative

Advances in islet cell biology over the past few years highlight a fundamental role for intra-islet endocrine cell interactions and δ-cells in the regulation of glycaemia. New insights into how cellular heterogeneity and individual-level heterogeneity effect hormone secretion have also emerged.

The year 2024 brought continuing research in the crucial field of adiposity-related health and polycystic ovary syndrome (PCOS). Although PCOS is considered a heterogeneous condition with regards to diagnostic criteria, complications and management, current research is advancing our understanding of the presentation and metabolic features of PCOS, as well as the benefits of lifestyle management.

In humans, weight loss as a result of lifestyle interventions, pharmacotherapy or bariatric surgery is often followed by weight regain. It is thought that cells retain an obesogenic memory that predisposes the body to return to the previous level of adiposity; however, the mechanisms that underlie this effect have been unclear. A new study has now demonstrated that adipocytes in humans and mice retain

It is well known that neuropeptides have a key role in regulating feeding behaviour. However, many aspects of the mechanisms behind neuropeptide control of satiety and hunger are unclear. A recent study in mice demonstrates that two neuropeptides, neuropeptide Y and αMSH, exert opposing effects on cAMP signalling in MC4R-expressing neurons in the paraventricular nucleus of the hypothalamus (PVHMC4R

Correction to: Nature Reviews Endocrinology https://doi.org/10.1038/s41574-024-01052-1, published online 13 November 2024.

A patient with longstanding type 1 diabetes mellitus has achieved insulin independence for at least 1 year after transplantation of autologous stem cell islets. These cells were differentiated from inducible pluripotent stem cells from adipose tissue and were transplanted into the rectus sheath of the abdominal wall.

Engineering pancreatic tissue transplants to treat diabetes mellitus will require knowledge of how different cell types regulate pancreatic development. A study in Cell Stem Cell characterizes the nuclear transcriptome in the second-trimester human fetal pancreas and shows that macrophages support pancreatic endocrine cell differentiation, proliferation and survival in vitro. To investigate whether

This October, the first joint meeting between the Irish Endocrine Society (IES) and the British Society for Endocrinology (SfE) was held in Belfast. On the opening morning, Miguel Debono (University of Sheffield) spoke to a packed room about the challenges of managing mild autonomous cortisol secretion. He discussed whether conservative management or adrenalectomy provided the best outcome for patients

The immune system is known to have a circadian rhythm; however, how circadian rhythms might affect immune homeostasis and physiology more broadly is unclear. A new paper now provides evidence that γδ T cells (a type of innate T cell) produce IL-17 in a rhythmic fashion, which is essential for de novo lipogenesis in adipose tissue and influences whole-body homeostasis. To confirm that IL-17A and IL-17F

Mammalian cellular machinery has evolved to function best at ~37 °C, making maintenance of core body temperature (at ~37 °C) critical for optimal organ function. The physiological importance of thermoregulation has been appreciated for many years, but our mechanistic understanding of the diversity and functioning of thermogenic mechanisms has advanced considerably in the past century. A brief analysis

Liothyronine treatment for some patients with hypothyroidism has preoccupied academics, clinicians and patients for decades, and is a controversial topic in thyroidology. Persistent symptoms are at the heart of this discourse and, contrary to scientific evidence, liothyronine use is increasingly common. Aetiologies and interventions beyond thyroid dysregulation and pharmacological approaches must be

Calorie restriction is known to extend lifespan in a wide range of species; however, the effects are variable and findings from animal models are often not applicable to humans, as the calorie restriction regimes are generally difficult to adhere to in the real world. Now, a paper has explored the effects and underlying mechanisms of several different methods of calorie restriction and dietary restriction

Insulin-like growth factor 1 (IGF1) is a key protein that contributes to control of an organism’s size after birth and during development, whereas IGF2 is the main regulator of growth and body size during fetal development. A study in Cell Reports describes a mechanism by which a microRNA produced from Igf2 regulates IGF1 to suppress growth in mice. The researchers then assessed the effect of miR-483

Efferent nerves from the dorsal motor nucleus of the vagus (DMV) connect to the gastrointestinal system and are thought to regulate digestion. The mechanisms by which the DMV controls nutrient absorption are under active investigation. A study published in Nature shows that a subpopulation of DMV neurons controls intestinal dietary fat absorption by modulating microvillus length in the jejunum. The

Atherosclerosis-related cardiovascular diseases are a major cause of death globally, and are expected to increase in prevalence with the rising incidence of obesity and type 2 diabetes mellitus. Despite being very common, there are still large knowledge gaps in our understanding of how atherosclerosis develops. Furthermore, most animal models for atherosclerosis rely on the use of a continuous high-fat

Multiple sclerosis (MS) targets the myelin sheath of central nervous system (CNS) neurons. MS is initiated by autoreactive CD4+ T cells, and obesity is known be associated with an increased risk of MS, particularly in women. A study in Cell Metabolism now identifies a female-specific mechanism by which obesity increases the risk of MS by promoting a pro-inflammatory T helper 1 (TH1) CD4+ T cell phenotype

Pharmacological therapies with incretin-based ‘multi-agonists’ are rapidly advancing the therapeutic landscape for obesity. The loss of skeletal muscle mass with these potent weight-loss agents is emerging as a possible side effect. It is therefore important to determine whether multi-agonists increase the risk of sarcopenia in susceptible patients.

Identifying neurological mechanisms that regulate feeding behaviour could help to advance the treatment and prevention of obesity and eating disorders. New research in mice has identified and localized a population of neurons that promotes eating to satiate hunger and reduces the desire to eat simply for pleasure. One subset of these DBBPENK neurons projects from the DBB to the paraventricular nucleus

Gene therapy holds tremendous promise for treating a wide range of hereditary and acquired diseases by delivering exogenous therapeutic nucleotide sequences into specific cells or tissues. Recent advances support the notion that gene therapy could offer a long-term cure for diabetes mellitus, something that current conventional pharmacotherapies cannot achieve.

Correction to: Nature Reviews Endocrinology https://doi.org/10.1038/s41574-024-01024-5, published online 15 August 2024.

It is well known that adipocytes are heterogeneous, and research about how best to identify and categorize adipocyte subclasses is ongoing. Thermogenic adipocytes are generally identified by the presence of UCP1; the futile creatine cycle is also an important thermogenic process in these cells. However, a lack of suitable models — particularly for beige adipose tissue — has stalled research into the

Two recent studies have unravelled novel modes of glucose-dependent insulinotropic polypeptide receptor (GIPR) signalling regulation. Kizilkaya et al. characterized the effect of changes in β-arrestin 2 coupling with naturally occurring GIPR coding variants, whereas Regmi et al. investigated GIPR expression profiles and functional regulation in adipocytes.

The gut microbiota strongly influences digestive and metabolic health. A study recently published in Nature Metabolism reports a link between hydrogen sulfide released by the gut microbiota and GLP-1 production in the intestines. The findings might have implications for treatment and prevention of the metabolic syndrome. To elucidate the mechanism behind this response, the researchers studied interactions

People with diabetes mellitus have substantially reduced numbers of pancreatic β-cells compared with healthy individuals. Now, a study in Science Translational Medicine demonstrates the efficacy of a dual tyrosine-regulated kinase 1A (DYRK1A) inhibitor treatment combined with a glucagon-like peptide 1 (GLP1) receptor agonist for increasing human β-cell mass in vivo. The researchers transplanted human

In female individuals, oestradiol preserves bone mass. However, oestradiol levels drop during lactation, which is also a time when calcium is being removed from the maternal bone. How bone mass is maintained in lactating female individuals has been unclear. A study published in Nature has now identified a new mechanism for maintaining bone mass, which involves brain–bone crosstalk. Next, the researchers

The first menstrual period, or menarche, is an important milestone in female sexual maturation. Studies have begun to determine how genetic variation influences age at menarche (AAM), with a large study recently published in Nature Genetics adding considerably to this knowledge base. To study the effect of common genetic variants on AAM, the researchers performed the largest genome-wide association