News & Views

A new study by Reverte-Salisa and colleagues identifies a molecular mechanism through which the cAMP-mediating protein EPAC1 controls the size of brown and beige adipose tissue. This finding opens the door for the development of pharmacological interventions to prevent the decline of brown adipose tissue in obesity and ageing, and thereby improve metabolic health.

Schuermans et al. report phospholipase A and acyltransferase 3 (PLAAT3) deficiency in patients with lipodystrophy and peripheral neuropathy. Their discovery adds to the growing list of genetic lipodystrophies due to deficiencies of enzymes involved in phospholipid biosynthesis, including 1-acylglycerol-3-phosphate O-acyltransferase 2 and choline phosphate cytidylyltransferase 1 A.

Over the past decade, the focus on modelling the human endometrium and its cyclical transformations has intensified, driven in part by the lack of notable progress in treating endometrial diseases. Gnecco and collaborators now unveil a cutting-edge endometrial organoid culture using synthetic hydrogels with endometrial niche peptides and epithelial and stromal cells.

A recent study by Zhou and colleagues proposed that low metabolic elasticity and gene elasticity are involved in the metabolic alterations observed in ageing and obesity. Here, we discuss some of their findings to provide a viewpoint on these potential new traits associated with metabolic health.

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 new diagnostic perspectives for endocrine diseases.

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.

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.

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.

Our lives are governed by three clocks: the social clock that organizes our lives with others (local time), the biological clock that controls our physiology (circadian time) and the sun clock that defines natural light and darkness. The more misaligned these clocks are, the higher our odds of developing certain diseases. ‘Social jetlag’ quantifies the difference between local and circadian time.

Cities with varied development types and green space are known to be protective for cardiometabolic health, while those with higher traffic-related pollution, access to calorie-dense food and poorer perception of safety are detrimental. These factors should be considered when planning urban developments in lower-income and middle-income countries to reduce cardiometabolic disease burden.

Tissue-resident stem cells have a central role in tissue regeneration, but other accessory cells are also required for efficient regeneration. A new study by Sastourné-Arrey and colleagues reveals a delicate mechanism of skeletal muscle regeneration through an unexpected type of inter-organ communication, in which stromal cells derived from adipose tissue support muscle regeneration.

Findings from the largest longitudinal study (315 participants) on psychosocial functioning in transgender or nonbinary youth after 2 years of gender-affirming hormone (GAH) therapy were recently published in New England Journal of Medicine. At a time of heightened politicization of this treatment, this study adds to the growing literature that demonstrates benefits of GAH therapy for transgender youth.

A transcriptomic analysis of endometriosis and comparison tissues has been conducted, revealing a rich and complex catalogue of single-cell-based expression data. This resource is an invaluable building block towards single cell profiling at scale, aiding research into endometriosis pathogenesis and new ways of diagnosing and treating the disease.

A new study reveals that exposure of pregnant mice to an endocrine disrupting chemical, bisphenol A, induces multi-transgenerational (up to six) inheritance of obesity in their descendants. This effect depends on CTCF-dependent chromatin reorganization in the sperm, a synergistic outcome of altered DNA methylation, RNA modification and long-range chromatin interactions.

The dorsal raphe nucleus (DRN) is emerging as a key regulator of food intake and energy expenditure but the molecular and functional heterogeneity of DRN neurons is largely unknown. A new study characterizes the role of glutamatergic DRN neurons in the control of food intake and identifies a pharmacological approach to target these neurons in obesity.

A considerable proportion of autoantibody-negative children with type 1 diabetes mellitus actually have monogenic forms of diabetes mellitus, which enables tailored treatment. Thus, a diagnosis of monogenic diabetes mellitus should be considered and genetically tested for in this group of patients, even if the clinical criteria for monogenic diabetes mellitus are not met.

Food odour recognition is involved in the food anticipatory response. A study in Nature Metabolism describes how the olfactory system differentially regulates metabolic adaptations depending on energy availability. These effects are mediated by a brain circuit involving the melanocortin system that controls systemic lipid utilization via the sympathetic nervous system.

Obesity is an important risk factor for severe COVID-19 and, possibly, for breakthrough SARS-CoV-2 infections in fully vaccinated people. Novel findings highlight how SARS-CoV-2 infects adipose tissue and promotes subclinical inflammation. Thus, also based on knowledge about endocrine dysfunction facilitating SARS-CoV-2 infection, a vicious cycle involving obesity, impaired metabolic health and COVID-19 might exist.

A recent publication in Cell Reports adds to the emerging consensus that metformin acts on the gut and kidneys to increase circulating levels of growth differentiation factor 15 (GDF15). However, the report also highlights circumstances in which the effects of metformin on body weight and energy balance seem to be independent of GDF15–GFRAL signalling.