Review Articles in 2025

This Review explores the translation of senotherapeutics into clinical practice for metabolic disorders. The authors discuss the relationship between metabolic disorders and cellular senescence, current and emerging therapies, and the challenges of translating senotherapeutics into clinical practice for metabolic disorders.

Oestrogen is a key regulator in many metabolic processes, particularly in adipose tissue. This Review discusses the role of oestrogen in adipose tissue metabolism and its wider implications for systemic metabolic health.

In this Review, the authors cover how leptin and melanocortin signalling affect the response to infection by regulating immune cells and the nervous system. The authors also discuss how these signalling pathways might be targeted to improve this response and the potential adverse effects that should be considered as these treatments are investigated.

This Review describes the metabolic functions of high-density lipoproteins (HDLs) and the structural and functional changes that they undergo in diabetes mellitus. The authors discuss how diabetes mellitus reduces the ability of HDLs to act as antioxidants, control inflammation and reduce the risk of cardiovascular disease.

In the past decade, the therapeutic scope of sodium–glucose cotransporter 2 (SGLT2) inhibitors has expanded beyond glycaemic regulation in the management of type 2 diabetes mellitus. In this Review, Lim et al. discuss data from clinical studies of SGLT2 inhibitors, demonstrating their multifaceted cardiovascular, metabolic and renal effects, and elucidate the diverse mechanisms underpinning these benefits.

In this Review, the authors discuss the mechanisms by which diabetes mellitus can lead to kidney damage and describe the clinical characteristics of diabetic kidney disease. The Review also covers current treatments for diabetic kidney disease and new therapies that are being developed.

The global incidence of thyroid cancer rose sharply after the 1980s despite stable mortality rates. Chen and Haymart outline known and emerging risk factors for thyroid cancer and discuss strategies to address the public-health issues of thyroid cancer overdiagnosis and overtreatment.

This Review summarizes our current understanding of how the skeleton regulates whole-body energy metabolism; rather than viewing bone as the core regulator of systemic energy metabolism, the authors suggest that bone contributes to the regulation of the complex processes underlying whole-body energy metabolism.

Medical nutrition therapy (MNT) is a key component of the management of type 2 diabetes mellitus (T2DM), and there is increasing evidence that specific dietary interventions can improve metabolic health in T2DM independently of weight loss. This Review assesses several key MNT strategies for their efficacy in T2DM management.

Cases of early-onset colorectal cancer (EOCRC) have risen alarmingly since the 1990s, alongside a surge in metabolic diseases, particularly obesity and type 2 diabetes mellitus (T2DM), among young populations. This Review synthesizes evidence regarding the association of obesity and T2DM with EOCRC.

Inpatient hyperglycaemia is found in the settings of known diabetes mellitus, previously undiagnosed diabetes mellitus and stress hyperglycaemia, and is associated with poor outcomes. Current approaches to managing inpatient hyperglycaemia and diabetes mellitus are outlined in this Review.

The body maintains its weight at a stable level by adjusting energy intake and output, but the system underpinning this weight regulation is not fully understood. This Review discusses models of body weight regulation and considers possible experimental scenarios to test which model is valid.

Consumption of ultra-processed foods (UPF) is increasingly linked to the development of obesity, on both an individual and a global scale. This Review assesses the role of UPF in obesity, examining the epidemiological evidence, biological mechanisms and implications for policymakers.

This Review outlines changes in endocrine and metabolic function that occur in various adipose tissue depots during ageing and explains how these alterations contribute to age-related decline in metabolic health. The Review also discusses how various treatments might slow this decline by improving adipose tissue function.

This Review briefly outlines the pathophysiology of type 1 diabetes mellitus and discusses therapeutic targets that have reached clinical trials, including immunotherapy, and how these treatments might change the future of the disease.

Hyponatraemia is associated with poor health outcomes and increased mortality, particularly for hospital inpatients. Risk of hyponatraemia increases with age due to comorbidities, polypharmacy and poor nutrition. This Review discusses the causes of hyponatraemia and its clinical management, with a particular focus on older populations.

Genetic mutations and environmental exposures cause severe endoplasmic reticulum (ER) stress in pancreatic β cells, which can culminate in diabetes mellitus. Lytrivi et al. describe the causes and consequences of ER stress for β cell development, function and survival, and debate emerging therapeutic approaches.

In this Review, the authors discuss different methods for assessing polygenic risk of diabetes mellitus and the utility of polygenic risk scores in classifying and screening for diabetes mellitus. The current limitations of these scores and ways of overcoming these limitations are also covered.

This article outlines evidence pointing to an important contribution of endocrine-disrupting chemicals to increasing rates of female reproductive disorders such as abnormal puberty, impaired fertility, premature menopause or polycystic ovarian syndrome reported over the past half a century.

Amylin is a peptide hormone involved in satiation. Amylin mimetics have potential as therapies for obesity and diabetes mellitus, but clinical development has proven challenging. This Review discusses the physiological roles of amylin and the current progress of amylin mimetic therapeutics.