Telomeres are nucleoprotein structures that comprise repetitive nucleotide sequences bound to specialized proteins at the ends (tails) of chromosomes. Often compared to the plastic tips on shoelaces, telomeres cap the ends of chromosomes to prevent them unravelling or tangling. When a cell divides, it loses base pairs from the ends of its telomeres so that, with ageing, the telomeres become shorter;

Since the discovery in the 1600s of microscopic organisms, scientists have investigated the relationship between our health and the microbes that surround and inhabit us. Nowadays, we acknowledge that some microbes are inherently pathogenic, but also that others live mutualistically on and within our bodies and contribute to maintaining our well-being. Yet, one prominent challenge remains: to convincingly

Fasting levels of glucose and susceptibility to type 2 diabetes mellitus (T2DM) are known to have a large genetic component. Genome-wide association studies (GWASs) have identified hundreds of loci associated with these traits. However, glucose homeostasis is highly complex, so there are likely to be many more loci that influence how blood levels of glucose are regulated. A study has now taken the

Women and men have different risk profiles for certain health conditions. For instance, differences in body composition between men and women are thought to partially underlie the different cardiometabolic risk profiles of men and women. Although men and women have similar levels of risk of obesity, their distribution of body adipose tissue differs. Men tend to carry excess weight as visceral adipose

Circadian rhythms, which are influenced by the light and dark that an organism is exposed to, have important effects on physiology. Traditionally, laboratory studies of circadian rhythms have used a 12-h light and 12-h dark experimental set up (photoperiod). However, apart from regions close to the Equator, the photoperiod varies throughout the year. A study in Cell Metabolism has now investigated

Deficiencies in leptin signalling cause severe early-onset obesity due to hyperphagia. A new study has investigated the long-term clinical outcomes for children with leptin signalling deficiency who do not receive treatment for the condition.

A new study in Nature has used a comprehensive multi-omics strategy in humans to uncover mechanisms by which carbohydrate metabolism by the gut microbiota contributes to insulin resistance.

Acute inflammation triggers activation of the hypothalamic–pituitary–adrenal axis, but whether it could also impede the adrenocortical response to adrenocorticotropic hormone remains controversial. A new study using preclinical models of acute inflammation demonstrates dysregulation of energy metabolism in adrenocortical cells, resulting in oxidative stress that induces disruption of steroidogenesis

In a new study, an ambulatory microdialysis system combined with ultrasensitive liquid chromatography-tandem mass spectrometry enabled the building of a 24-h high-resolution profile of adrenal steroids in the tissue by sampling interstitial fluid in 214 healthy volunteers. Daily and ultradian variations of eight free steroids, including cortisol and aldosterone, have been demonstrated, which opens

Tales of vampirism date back to the ancient Egyptian goddess of war and healing, Sekhmet, whose consumption of human blood fuelled her rage and power. Similar concepts pervade human history; for instance, vampires and the undead consume blood of the living to survive and maintain a youthful appearance. Many historical beliefs and ancient practices associate youthful revitalization and longevity with

A pressing need exists for effective drugs to treat nonalcoholic fatty liver disease (NAFLD), which affects around a quarter of the population worldwide. A new study in Cell Metabolism now shows that a bile acid, hyodeoxycholic acid (HDCA), is depleted in patients with NAFLD and shows therapeutic potential in mouse models of NAFLD.

Most women experience vasomotor symptoms during menopause, which considerably affect their quality of life. While vasomotor symptoms can be substantially reduced with menopausal hormone therapy, many women are unable or choose not to take hormone therapy. Now, studies have demonstrated that neurokinin 3 receptor antagonists have a level of effectiveness against vasomotor symptoms that is similar to

Previous work has demonstrated that a high-fat diet (HFD) induces hypothalamic inflammation and gliosis in rodents, and that people with obesity have hypothalamic gliosis. In addition, a study showed that inflammatory signalling by microglia (brain macrophages) has a direct role in diet-induced obesity. However, until now, the connection between microglial inflammatory signalling and glucose tolerance

The adipose tissue microenvironment influences the expression of UCP1 (the key regulator of non-shivering thermogenesis) in white adipocytes. However, the majority of studies have been performed in male mice, so the effect of mammary gland ductal cells on adipocyte thermogenesis in mammary gland white adipose tissue (mgWAT) was unclear. A new study in Nature identifies a role for mammary gland ductal

Obesity is a serious and growing socioeconomic concern that affects almost half of adults in the USA, and is an independent risk factor for metabolic disorders, including non-alcoholic fatty liver disease, type 2 diabetes mellitus and heart failure. Anti-obesity public health initiatives remain ineffective, with increasing obesity rates and a limited impact of diet and exercise interventions. Pharmacotherapy

Body weight has a large genetic component; >1,000 single-nucleotide polymorphisms are associated with BMI. Many of the most common variants are found in the introns of FTO, including the rs1421085 T>C variant. The effects of this variant were unclear; a new study indicates it has a role in brown adipose tissue thermogenesis.

Funcke et al. shed light on the management of leptin replacement therapy in monogenic obesity by identifying two LEP variants with antagonistic functional effects. Their groundbreaking study emphasizes the urgent need for in-depth understanding of the genetic factors involved in obesity to pave the way for tailored interventions.

Pregnancy is a state of cooperation and conflict between mother and offspring, which ensures that the nutrient demands of both are met. However, the mechanisms by which the fetus manipulates maternal metabolism are unclear. A new study in Cell Metabolism demonstrates a key role in mice for the paternally inherited imprinted gene Igf2, which encodes insulin growth factor 2 (IGF2), in placenta endocrine

Heart disease is currently considered the leading cause of death worldwide, and coronary artery disease — the most common type of heart disease — underlies most cases of myocardial infarction. Myocardial infarction arises from the rupture of an atherosclerotic plaque, which causes the formation of a clot and occludes the blood supply in large epicardial coronary arteries. This disrupted blood flow

People with obesity are often at high risk of developing non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH); however, the role that different liver macrophage populations can have in NAFLD and NASH is unclear. A new study in Nature Metabolism has identified a population of resident liver myeloid cells that protect against metabolic impairment in the liver in the context

Obesity affects more than 10% of the world’s population and is now considered to be a global epidemic. This chronic disease results from an imbalance between energy consumption and expenditure. On a simplistic level, this imbalance can be caused by long-term excess consumption of food and a sedentary lifestyle, which combine to promote adipose tissue expansion. Adipose tissue eventually also becomes

Cases of cardiometabolic diseases, including type 2 diabetes mellitus, obesity and the metabolic syndrome, are at crisis levels in industrialized countries. Circadian misalignment, caused by our modern 24-h culture of working and eating late, excessive light exposure at night, and reduced sleep, increases the risk of developing these disorders. In particular, shift workers, who are regularly exposed

Prior to the 1950s, cancer therapy largely comprised two pillars: surgery and radiation. There was a clear need to develop medicines to treat the disease and/or its symptoms, but the lack of mechanistic insights into cancer biology constrained drug discovery efforts. Furthermore, at that time, micrometastasis was largely overlooked, and the therapeutic utility of tumour markers was also not readily

The hormone growth differentiating factor 15 (GDF15) suppresses energy intake and induces weight loss in rodents and non-human primates. In mice, the mechanism involves appetite suppression, through GDF15 signalling via its receptor GFRAL in the hindbrain. A new study in Nature now shows that GDF15 also facilitates weight loss by increasing energy expenditure in skeletal muscle.

A new study convincingly demonstrates a deficiency of pituitary oxytocin secretion in patients with vasopressin deficiency. Neuropsychological evaluations of these patients indicate increased anxiety and reduced prosocial behaviours, thereby characterizing the phenotype of the first documented disorder of oxytocin deficiency in humans.

The prevalence of obesity is rapidly increasing worldwide and is estimated to be the cause of approximately 3 million deaths per year globally. Countless weight-loss strategies have therefore been investigated and marketed. However, most have failed to show long-term effects on sustained weight loss. Furthermore, weight regain often occurs and, until the past few years, only surgical solutions have

Progenitor cells are important for human health, as they are essential components of tissue development and repair throughout the life course. However, little is known about progenitor cells in adipose tissue, even though this tissue is a key factor in metabolic health. Now, two complementary papers published in Nature Metabolism have contributed to a leap in our understanding of adipose tissue progenitor

A high-fat, low-carbohydrate diet, known as a ketogenic diet, can be used to starve glucose-hungry tumour cells in cancer. Indeed, studies in humans and preclinical models indicate that a ketogenic diet has an anti-inflammatory effect and could slow tumour growth. A new paper in Cell Metabolism reports a mechanism by which a ketogenic diet slows tumour growth in mice, but at the expense of corticosterone

Pancreatic islet cell replacement therapy is a promising strategy for patients with type 1 diabetes mellitus, but the scarcity of organ donors and need for immunosuppression hamper its wide application. Huang and colleagues developed an efficient method to redirect the fate of primary human gastric stem cells, generated from stomach tissue, towards insulin-producing β-cells.

Hypothalamic agouti-related peptide (AgRP)-expressing neurons are stimulated by the orexigenic hormone ghrelin to induce food intake. However, the ghrelin-dependent signalling mechanisms in these neurons are not well understood. A new study identifies a role for calcium/calmodulin-dependent protein kinase ID (CaMK1D) in mediating ghrelin-dependent food intake by AgRP neurons.

Adrenocortical carcinoma (ACC) is a rare aggressive cancer of the adrenal cortex with peak incidence in older adults and no effective targeted therapies. A study published in Nature Aging has used a mouse model of age-dependent adrenal cancer to identify a tumour-protective role for myeloid immune cells that is enhanced by androgens.

The obesogenic environment is a key factor in the obesity epidemic that affects many, but not all, humans across the world. While some people are prone to obesity, others are protected (or partially protected) from gaining excess adipose tissue mass. Indeed, individuals with constitutional thinness (found at the far-left end of the BMI spectrum) self-report that they are completely resistant to weight

The use of artificial sweeteners and sugar substitutes has increased substantially in the past few years due to their low-calorie content and presumed health benefits. They are commonly used in beverages and food that can be bought in almost every supermarket. Artificial sweeteners are often recommended to individuals with type 2 diabetes mellitus, to reduce caloric intake and promote glycaemic control

Human pluripotent stem cell-derived islets contain insulin-producing β-cells and could be an important therapeutic avenue for treating type 1 diabetes mellitus. However, currently, there are notable differences between stem cell-derived islets and primary human islets. A new paper has set out to define these differences.

Osteoporosis is a disease characterized by a low level of bone formation (by osteoblasts) and an excess of bone resorption (by osteoclasts), in part due to increased differentiation of osteoclasts from their precursor cells, bone marrow-derived monocytes (BMDMs). A new study finds that deficiency in the deacetylase SIRT2 in hepatocytes reduces bone loss in mouse models of osteoporosis.

Mitochondria are ATP-producing metabolic hubs and regulatory centres for cells. Mitochondria are associated, either directly or indirectly, with almost every disease or physiological dysfunction that is understood at the cellular level. These mitochondrial underpinnings of disease were not always taken as a given; modern understanding of mitochondria and metabolism is built upon work published in the

Artificial intelligence has already revolutionized various fields in medicine and research. Due to the complex and interconnected nature of the endocrine system, it is an ideal area to further exploit and maximize the potential benefits of artificial intelligence.

Acarbose is widely used to treat type 2 diabetes mellitus (T2DM). However, patients vary in how well they respond to acarbose, and some patients develop resistance to acarbose after long-term use. The mechanisms underlying the varied response and drug resistance have been unclear. Now, a study published in Nature Metabolism has demonstrated that a particular type of gut bacteria is involved in these

The path to becoming a clinical academic researcher is arduous and convoluted, with many hurdles. A good mentor is key to growth and development, not only as one embarks on the journey, but also as a ‘sounding board’ throughout one’s career.

Type 1 diabetes mellitus (T1DM) can be predicted, and immune therapy can alter the progression of the disease. The FDA’s approval of teplizumab as the first disease-modifying therapy for T1DM and the first therapy aimed at delaying the clinical onset of any immune-mediated disease represents a paradigm shift in the treatment of T1DM.