News & Views in 2022

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.

Host–microorganism circadian dynamics are key contributors to metabolic health. In addition, diet composition and timed feeding affect gut microbiota diurnal rhythms, with high-fat diets altering the composition of the gut microbiota and dampening circadian rhythms throughout the intestine. A recent study shows that time-restricted feeding of a high-fat diet restores the rhythms of small bowel host–microorganism interactions, preventing diet-induced obesity in mice.

A randomized controlled trial demonstrates that using lower glycaemic criteria for diagnosing and treating gestational diabetes mellitus than currently used increases disease prevalence but does not reduce the risk of large-for-gestational-age infants across a population. However, individuals with mild hyperglycaemia who would otherwise remain undiagnosed experienced important health benefits from treatment.

A recent article from Science Translational Medicine demonstrated the importance of pancreas-derived mesenchymal stem cells (PMSCs) for rejuvenating the exocrine pancreas in two mouse models of type 1 diabetes mellitus. PMSCs boosted levels of IL-6 in T helper 1 and T helper 17 cells, which transiently triggered IFNγ and TNF expression and curtailed IL-17 expression to shelter β-cells from immune-mediated damage.

Non-nutritive sweeteners (NNSs) seem to be a good substitute for sugar; they have the much-desired sweet taste but lack caloric content. A multi-arm randomized controlled trial assessing the effects of four NNSs on human metabolic health and the gut microbiome was recently published in Cell. The results further feed the long-standing debate on whether NNS use is indeed wholesome for human health.

The long non-coding RNA HOTAIR is exclusively expressed in gluteofemoral subcutaneous adipose tissue (GSAT) and is functionally required for GSAT adipocyte differentiation. A genetic variation analysis showed that the minor allele of rs1443512 is associated with reduced HOTAIR expression and decreased adipose tissue mass in the leg and gynoid regions.

Thermogenic brown and beige adipocytes have gained much attention as potential therapeutic targets in obesity and related cardiometabolic disease. A recent paper in Nature identifies inosine, released from apoptotic brown adipocytes, as an inducer of thermogenic adipose tissue, thereby uncovering an unexpected and novel mechanism of adipose tissue plasticity.

In a recent issue of Cell Reports, Xi et al. reported on their studies of an anti-glucagon receptor antibody in several mouse models of insulin-deficient diabetes mellitus, in which they show substantial increase in β-cell mass from enhanced replication and transdifferentiation of glucagon-expressing α-cells to insulin-expressing β-cells.

Adipocyte insulin resistance is a driving force for systemic insulin resistance. Advances in human stem cell culture have established conditions for human adipocytes that give rise to a reproducible population of adipocytes that retain a high level of insulin sensitivity, paving the way for high throughput screening approaches.

Sodium–glucose cotransporter 2 (SGLT2) inhibitor treatment affects central regulation of appetite and satiety, which results in increased carbohydrate intake. It has now been demonstrated that these effects might be blunted by combining SGLT2 inhibitors with glucagon-like peptide 1 receptor agonists to further facilitate weight loss in patients with type 2 diabetes mellitus.

A recent study has generated compelling experimental data on the role of GPR177 and WNT5a in the pathogenesis and treatment of painful diabetic neuropathy (PDN). The clinical value of these translational findings should be interpreted with caution. However, the limited efficacy of current treatments for PDN warrants further clinical studies on these novel pathways.

By identifying a new means of communication between endothelial cells and adipocytes, researchers provide evidence that the endothelial cells actively provoke lipid release from adipocytes to support capillary growth. This crosstalk ultimately helps to maintain metabolic health in obesity.

Stem cells in the pituitary master gland remain mystifying; moreover, they have hardly been explored in humans. A new study applied transcriptome and chromatin accessibility profiling at single-cell resolution to human postmortem pituitary glands from individuals of different ages, thereby providing insights into the heterogeneity and regulatory mechanisms of the projected human pituitary stem cell population.

A recent paper published in PLoS Biology reported the application of lipidomics in predicting the incidence of type 2 diabetes mellitus and cardiovascular diseases in a population cohort. The study demonstrates the role of lipidomics in prediction of diseases and translational research, which could herald the beginning of an era of quantitative lipidomics.

Diet is a major modifiable risk factor for noncommunicable diseases. However, studies are inconsistent on the associations between diet quality and education, income and food access. A new study brings together novel big data sources and highlights the need for strong action on the social determinants of health in order to improve population diets.

A new paper explores genetic risk factors for polycystic ovary syndrome (PCOS) and non-reproductive PCOS phenotypes in women and men. This work affirms that PCOS is indeed a metabolic disorder, that ovarian function is not required for cardiometabolic features and that this condition has implications for both men and women.

Nelson and colleagues compare whole body, skeletal muscle and white adipose tissue insulin resistance in inbred mouse strains fed a chow or a Western diet. They report large strain-related differences in diet-induced effects on weight gain and insulin action, and demonstrate that tissue-specific insulin sensitivity can be disentangled from systemic insulin resistance.