Reviews & Analysis

The skeletal muscle clock directs a circadian programme of gene expression that is fundamental to both skeletal muscle and systemic energy metabolism. Notably, exercise timing can influence the skeletal muscle clock, which provides a rationale for exploring its potential role as a chronotherapeutic strategy.

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.

Organoid systems have great potential to improve the study of diseases such as diabetes mellitus. This Review assesses the progress in developing pancreatic organoids and bioengineered systems for modelling diabetes mellitus and its complications.

This Review outlines evidence that the gut microbiota is involved in regulating body weight homeostasis. In addition, the opportunities, limitations and challenges of using gut microbiota-related approaches as a means to achieve and maintain a healthy body weight in people with overweight or obesity are discussed.

In May 2022, the WHO released global targets for diabetes mellitus. In this Viewpoint, experts from around the world discuss the challenges and opportunities in applying these targets.

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.

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.