Obesity and type 2 diabetes mellitus (T2DM) are increasing in prevalence owing to decreases in physical activity levels and a shift to diets that include addictive and/or high-calorie foods. These changes are associated with the adoption of modern lifestyles and the presence of an obesogenic environment, which have resulted in alterations to metabolism, adaptive immunity and endocrine regulation. The

Fat accumulation outside subcutaneous adipose tissue often has unfavourable effects on systemic metabolism. In addition to non-alcoholic fatty liver disease, which has received considerable attention, pancreatic fat has become an important area of research throughout the past 10 years. While a number of diagnostic approaches are available to quantify pancreatic fat, multi-echo Dixon MRI is currently

By mapping the spatial organization of adipose tissue, Bäckdahl and colleagues identify adipocyte progenitor structures as well as three subclasses of adipocytes with different molecular functions, including insulin sensitivity and leptin signalling.

Endocrine cells within the pancreatic islets of Langerhans are heterogeneous in terms of transcriptional profile, protein expression and the regulation of hormone release. Even though this heterogeneity has long been appreciated, only within the past 5 years have detailed molecular analyses led to an improved understanding of its basis. Although we are beginning to recognize why some subpopulations

The effects of the gut microbiota on human health are tremendous. Now, a study on the microbiota of wild mice sheds light on how the microorganisms that inhabit the gut between birth and weaning determine resistance to weight gain during adulthood.

The worldwide incidence of obesity and its sequelae, such as type 2 diabetes mellitus, have reached pandemic levels. Central to the development of these metabolic disorders is adipose tissue. White adipose tissue stores excess energy, whereas brown adipose tissue (BAT) and beige (also known as brite) adipose tissue dissipate energy to generate heat in a process known as thermogenesis. Strategies that

Melanin-concentrating hormone (MCH) is a small cyclic peptide expressed in all mammals, mainly in the hypothalamus. MCH acts as a robust integrator of several physiological functions and has crucial roles in the regulation of sleep–wake rhythms, feeding behaviour and metabolism. MCH signalling has a very broad endocrine context and is involved in physiological functions and emotional states associated

A new paper reports that the protein isthmin 1 is secreted by mature adipocytes and triggers a signalling cascade similar to that of insulin. The novel adipokine acts through an unidentified receptor tyrosine kinase and, at pharmacological doses in mice, isthmin 1 ameliorates metabolic disturbances associated with type 2 diabetes mellitus, including hyperglycaemia and liver steatosis.

An emerging feature of type 1 diabetes mellitus and type 2 diabetes mellitus is their association with pulmonary fibrosis, which negatively affects the prognosis of patients. Here, we provide a brief update of the field and the remaining open questions.

Up to one in four women with type 1 diabetes mellitus (T1DM) also have polycystic ovary syndrome (PCOS). Under subcutaneous insulin administration, systemic hyperinsulinism might trigger PCOS in women predisposed to the condition. However, very little is known about the long-term consequences of androgen excess in women with T1DM, and management guidelines are lacking.

A new Consensus Statement calls for precautionary action around the use of paracetamol in pregnancy, through focused research efforts and by increasing awareness.

Paracetamol (N-acetyl-p-aminophenol (APAP), otherwise known as acetaminophen) is the active ingredient in more than 600 medications used to relieve mild to moderate pain and reduce fever. APAP is widely used by pregnant women as governmental agencies, including the FDA and EMA, have long considered APAP appropriate for use during pregnancy when used as directed. However, increasing experimental and

Fracture risk is increased in patients with type 2 diabetes mellitus (T2DM). In addition, these patients sustain fractures despite having higher levels of areal bone mineral density, as measured by dual-energy X-ray absorptiometry, than individuals without T2DM. Thus, additional factors such as alterations in bone quality could have important roles in mediating skeletal fragility in patients with T2DM

Autophagy is an evolutionarily conserved, lysosome-dependent catabolic process whereby cytoplasmic components, including damaged organelles, protein aggregates and lipid droplets, are degraded and their components recycled. Autophagy has an essential role in maintaining cellular homeostasis in response to intracellular stress; however, the efficiency of autophagy declines with age and overnutrition

Although usually benign, anterior pituitary tumours occasionally exhibit aggressive behaviour, with invasion of surrounding tissues, rapid growth, resistance to conventional treatments and multiple recurrences. In very rare cases, they metastasize and are termed pituitary carcinomas. The time between a ‘classical’ pituitary tumour and a pituitary carcinoma can be years, which means that monitoring

Immune checkpoint inhibitor therapies induce potent anti-tumour immunity as well as immune-related adverse events that manifest as autoimmune disease — particularly thyroiditis. Translational studies and preclinical models are beginning to unravel the molecular processes that mediate these adverse events; this knowledge might enable the development of ICIs with anti-tumour efficacy and improved safety

Growth hormone (GH) deficiency (GHD) in children is defined as impaired production of GH by the pituitary gland that results in growth failure. This disease might be congenital or acquired, and occurs in isolation or in the setting of multiple pituitary hormone deficiency. Isolated GHD has an estimated prevalence of 1 patient per 4000–10,000 live births and can be due to multiple causes, some of which

The liver is often thought of as a single functional unit, but both its structural and functional architecture make it highly multivalent and adaptable. In any given physiological situation, the liver can maintain metabolic homeostasis, conduct appropriate inflammatory responses, carry out endobiotic and xenobiotic transformation and synthesis reactions, as well as store and release multiple bioactive

Adipose tissue macrophages (ATMs) have important roles in the regulation of inflammatory responses and insulin resistance in obesity. A new study reports that a subpopulation of ATMs, TIM4+ resident ATMs, modulate adipocyte size via platelet-derived growth factor-CC production during development and diet-induced adipose tissue expansion.

Pancreatic β-cell dysfunction contributes to type 2 diabetes mellitus (T2DM) pathogenesis. However, human islet studies have revealed few consistent molecular changes in T2DM, owing partly to technical and biological confounding factors. A new multi-omics study of islets from well-phenotyped living donors attempts to overcome these limitations to catalogue T2DM-associated molecular changes.

At the time of its first clinical application 100 years ago, insulin was presented as the cure for people with diabetes mellitus. That transpired to be an overstatement, yet insulin has proven to be the lifesaver for people with type 1 diabetes mellitus and an essential therapy for many with type 2 diabetes mellitus or other forms of diabetes mellitus. Since its discovery, insulin (a molecule of only

Growth differentiation factor 15 (GDF15) is a member of the TGFβ superfamily whose expression is increased in response to cellular stress and disease as well as by metformin. Elevations in GDF15 reduce food intake and body mass in animal models through binding to glial cell-derived neurotrophic factor family receptor alpha-like (GFRAL) and the recruitment of the receptor tyrosine kinase RET in the

An increasing number of transgender and gender-diverse (TGD) youth (early pubertal through to late adolescent, typically 9–10 through to 18 years of age) are seeking medical services to bring their physical sex characteristics into alignment with their gender identity — their inner sense of self as male or female or somewhere on the gender spectrum. Compelling research has demonstrated the clear mental

Harnessing the thermogenic, energy-expending capacity of adipocytes has the potential to combat metabolic disorders. Although β3-adrenergic receptor agonists are the best-known activators of thermogenesis, they carry considerable cardiovascular risks. A new study demonstrates the ability of G protein-coupled receptor 3 to intrinsically drive adipose thermogenesis independent of β3-adrenergic receptor

Biological sex, fluctuations in sex steroid hormones throughout life and gender as a social construct all influence every aspect of health and disease. Yet, for decades, most basic and clinical studies have included only male individuals. As modern health care moves towards personalized medicine, it is clear that considering sex and hormonal status in basic and clinical studies will bring precision

Metabolically healthy obesity (MHO) describes the presence of obesity with limited or no features of poor metabolic health. MHO might be a transient state associated with long-term health complications. A recent study highlights that MHO is associated with an increased risk of heart failure. Obesity, in all forms, requires intervention.

Bariatric surgery induces sustained weight loss and metabolic benefits via notable effects on the gut–brain axis that lead to alterations in the neuroendocrine regulation of appetite and glycaemia. However, in a subset of patients, bariatric surgery is associated with adverse effects on mental health, including increased risk of suicide or self-harm as well as the emergence of depression and substance

Polycystic ovary syndrome (PCOS) is the main cause of female infertility worldwide and is associated with a substantially increased lifetime risk of comorbidities, including type 2 diabetes mellitus, psychiatric disorders and gynaecological cancers. Despite its high prevalence (~15%) and substantial economic burden, the aetiology of PCOS remains elusive. The genetic loci linked to PCOS so far account

The pharmacological treatment of pituitary tumours is based on the use of stable analogues of somatostatin and dopamine. The analogues bind to somatostatin receptor types 2 and 5 (SST2 and SST5) and dopamine receptor type 2 (DRD2), respectively, and generate signal transduction cascades in cancerous pituitary cells that culminate in the inhibition of hormone secretion, cell growth and invasion. Drug

The past 50 years have seen a growing ageing population with an increasing prevalence of type 2 diabetes mellitus (T2DM); now, nearly half of all individuals with diabetes mellitus are older adults (aged ≥65 years). Older adults with T2DM present particularly difficult challenges. For example, the accentuated heterogeneity of these patients, the potential presence of multiple comorbidities, the increased

A new study has reported genetic evidence that MEK–ERK signalling is needed by β-cells, both for maintenance of β-cell mass and for optimization of insulin release. Their results point towards a new challenge of disentangling ERK signalling across multiple time scales.

Diabetes mellitus is characterized by the failure of insulin-secreting pancreatic β-cells (or β-cell death) due to either autoimmunity (type 1 diabetes mellitus) or failure to compensate for insulin resistance (type 2 diabetes mellitus; T2DM). In addition, mutations of critical genes cause monogenic diabetes. The endoplasmic reticulum (ER) is the primary site for proinsulin folding; therefore, ER proteostasis