Reviews & Analysis

Understanding of intermuscular adipose tissue has expanded over the past few years. This Review discusses the specific role of intermuscular adipose tissue in metabolic diseases in humans and in animal models, with a particular emphasis on the quantity and biological properties of this unique adipose tissue.

The year 2022 has been notable for game-changing early progress in clinical trials with stem cell islets; durable and promising 20-year data with long-term outcomes in clinical islet transplantation; and the development of locally protective or gene-editing-based approaches to avoid long-term immunosuppression.

Calorie restriction and timed dietary intake are two approaches known to increase lifespan or delay age-associated diseases. New studies reveal the importance of the ‘how much’ and ‘when’ of dietary intake in ageing modulation and collectively demonstrate how protection of the internal clock by diet can delay the ageing process.

Adipose tissue is highly versatile, dynamic and essential for metabolic health. In 2022, several exciting discoveries provided a high-resolution view of cellular composition and cell–cell communication within the adipose niche, and revealed how adipose tissue communicates with other organs and modulates metabolism during normal and pathophysiological states.

In 2022, the activation mechanism of TSH receptor (TSHR) by TSH and autoantibodies was demonstrated, monocarboxylate transporter 8 (MCT8) deficiency was corrected with gene therapy in mice and mutant thyroid hormone receptor α (TRα) was activated with a synthetic ligand. These results offer translational perspectives for patients with common and rare diseases affecting these proteins.

Glucagon-like peptide 1 (GLP1) analogues are licensed options for obesity, but new treatments are required to obtain better weight loss and to directly address other co-morbidities, such as non-alcoholic fatty liver disease. Research published in 2022 shows that co-agonist combinations of GLP1 with other hormones provide clinically important advances.

This Review highlights the extrapancreatic actions of the incretin hormones gastric inhibitory polypeptide and glucagon-like peptide 1. These peptides are active on tissues with cardiometabolic relevance, such as liver, adipose tissue, muscle, the immune, kidney, heart, blood vessels and the central nervous system.

There is growing awareness of differences in susceptibility to SARS-CoV-2 infection and COVID-19 severity between men and women. This Review assesses the evidence for this disparity and its potential causes, with a focus on the role of sex hormones.

In this Viewpoint, experts in the fields of medical therapy, adipocyte biology, exercise and muscle, bariatric surgery, genetics, and public health give their perspectives on current and future progress in addressing the rising prevalence of obesity.

This Review presents evidence that points to a critical role for metabolic pathways in influencing processes that support the early stages of tumour development, provides examples of the role of metabolic networks intrinsic to cancer cells in tumour progression and outlines how environmental factors can affect tumour incidence.

Cardiorenal diseases are common in patients with type 2 diabetes mellitus (T2DM), with substantial morbidity and premature mortality. This Review discusses how atherosclerotic cardiovascular disease and cardiorenal diseases can be prevented in T2DM, considering evidence from clinical trials and its implementation in clinical practice.

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.

Exercise has many beneficial effects; however, glycaemia needs to be carefully managed in patients with type 1 diabetes mellitus undertaking exercise. This Review characterizes the exercise response in people with type 1 diabetes mellitus and provides clinical management strategies to address glucose control around exercise.

Hypoglycaemia is a common occurrence in people with type 1 diabetes mellitus, and can have serious consequences. This Review defines hypoglycaemia in type 1 diabetes mellitus, and also outlines its frequency, risk factors and adverse outcomes. Ways to prevent and treat this complication of insulin therapy are also discussed.

Bariatric surgery induces weight loss and can trigger remission of type 2 diabetes mellitus (T2DM) but may also lead to post-bariatric hypoglycaemia. This Review examines surgery-induced changes in glucose regulation and the potential mechanisms responsible for the resolution of T2DM and induction of hypoglycaemia.

Insufficient sleep and circadian misalignment contribute to obesity risk. This Review discusses how modern society disrupts sleep, it considers evidence from human studies on how sleep disruption affects energy expenditure, appetite hormones and food intake, and discusses some potential strategies to reduce the adverse effects of sleep disruption.

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.