Reviews & Analysis

The carbohydrate-responsive element binding protein (ChREBP) senses intracellular carbohydrates and activates many target genes, including those crucial for de novo lipogenesis in hepatocytes. This Review discusses mechanisms that regulate ChREBP activity, the role of ChREBP in nonalcoholic liver disease (NAFLD) and emerging NAFLD drug targets.

Mammals are highly susceptible to being permanently influenced by maternal factors and nutritional status during the intrauterine and early postnatal periods. This Review summarizes and discusses the potential role of several adipokines, including leptin and adiponectin, in inducing metabolic programming through their effects during development.

Small rodents are still the most widely used animal model to study the pathophysiology of diabetes mellitus but non-rodent species can also provide valuable insights. The advantages and disadvantages of selected animal models of diabetes mellitus are outlined in this Review.

This Review highlights mechanisms of glucagon secretion from pancreatic α-cells, including paracrine actions in islets and α-cell–β-cell crosstalk. Dysregulated glucagon secretion in metabolic diseases is also considered and the clinical potential of targeting glucagon is discussed.

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.

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.

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.

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.

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.

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.

Life stress is known to affect the development and progression of metabolic diseases. This Review discusses the pathophysiological mechanisms underlying the association between stress and metabolic disease, and evaluates the epidemiological evidence for the influence of stress on metabolic disease.

This Review discusses the ATP-binding cassette (ABC) proteins ABCB1 and ABCC1 and their preferential cellular export of cortisol and corticosterone, respectively. The article also explores the potential to select therapeutic glucocorticoids on the basis of their different tendencies for export to avoid harmful adverse effects.

Membrane trafficking is essential for the sorting and distribution of several different types of cargo between different intracellular compartments and the plasma membrane. In this Review, advances in understanding the contribution of the endosomal system to metabolic physiology and pathology are outlined.

The mammary gland is responsible for lactation and is regulated by the coordinated actions of reproductive and metabolic hormones. This Review discusses the hormonal regulation of lactation, hormonal functions of the mammary gland, the hormone composition of human milk, and endocrine and metabolic diseases that cause lactation insufficiency.