News & Views

Bile acids are increasingly recognized for their broad metabolic effects, including the regulation of glucose homeostasis. In a recent study published in Nature Metabolism, researchers provide compelling evidence that alteration in bile acid flux — namely, in intestinal absorption and faecal secretion — can directly influence prandial glucose metabolism.

Advances in biomedical research often result from a straightforward formula: a good working hypothesis, a set of dedicated investigators, and access to calorimetric chambers and a laboratory scale. The success of this approach has again been demonstrated in a new Cell Metabolism report showing that tirzepatide induces weight loss through partially distinct mechanisms in mice and humans.

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.

Having more refined mouse models of metabolic dysfunction-associated steatotic liver disease (MASLD; also known as nonalcoholic fatty liver disease) will help to advance research into this disease. In their study, Jeong and colleagues use streptozotocin together with a high-fat diet for 6–60 weeks to investigate the progression from MASLD to hepatocellular carcinoma.

Brown adipocytes are increasingly recognized as a promising therapeutic target for metabolic disorders. Research published in Advanced Science now presents evidence that these cells might also be useful for leukaemia therapy. The study demonstrates that activation of brown adipocytes deprives leukaemia cells of glucose, which reveals a potential new avenue for leukaemia treatment.

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.

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.