Reviews & Analysis

Obesity activates stress-activated protein kinases (SAPKs), such as the p38 and JNK stress kinases, in several tissues, including adipose, liver, skeletal muscle, immune organs and the central nervous system. This Review discusses the role of SAPKs in metabolic control and highlights important discoveries in the field.

A need exists for rapid, cheap and noninvasive diagnostic tests for type 2 diabetes mellitus (T2DM). Now, a smartphone-based photoplethysmography screening test has been reported to detect T2DM based on a novel digital vascular biomarker, distinct from blood glucose, analysed with deep learning.

This Review summarizes the adaptations to lipid metabolism that occur in skeletal muscle in response to either a high-fat diet or exercise training. In addition, obesity-associated impairments in fatty acid oxidation capacity and the importance of exercise for overcoming lipid metabolic inflexibility in obesity are discussed.

Dipeptidyl peptidase 4 inhibitors are now widely used in the treatment of patients with type 2 diabetes mellitus. This Review discusses the use of the five main dipeptidyl peptidase 4 inhibitors for this purpose, highlighting their benefits and risks.

Typically, our mechanistic understanding about links between exercise and mortality come from epidemiological and short-period training studies. An initial transcriptomic study shows that decades-long endurance training shifts skeletal muscle gene activity to favour cellular respiration, upholding the consilience of evidence for ‘aerobic’ as a central feature of health and longevity.

Sodium–glucose cotransporter type 2 inhibitors (SGLT2is) are used for the treatment of type 2 diabetes mellitus. This Review provides an in-depth overview of the role of SGLT2is as glucose-lowering agents and as cardiovascular and renal protective agents.

During the past 5 years, a number of notable research advances have been reported for neuroendocrine cancers of the gastrointestinal tract. This Review provides an up-to-date summary of the research advances that have improved the clinical management of these cancers.

With immune checkpoint blockade (ICB) technologies increasingly being used in cancer immunotherapy, early data suggest that ICB therapies could be effective in thyroid cancer. This Review discusses our current knowledge of the immune response in thyroid cancers, the latest and ongoing immune-based approaches and the future of immunotherapies in thyroid cancer.

Lipoedema is a disorder characterized by the symmetrical accumulation of mechanically compliant adipose tissue in the proximal extremities. This Perspective article proposes a new mechanism for lipoedema, in which dysfunctional caveolin 1 in adipose tissue becomes uncoupled from key feedback loops with matrix metalloproteinase 14, oestrogen receptor and prospero homeobox 1.

Bone marrow adipose tissue secretes adipokines and is involved in glucose and lipid metabolism. The confined bone marrow cavity could partially explain the resistance of bone marrow adipose tissue to insulin-mediated glucose uptake and its role in systemic energy regulation.

Fibroblast growth factor 21 (FGF21) confers considerable pharmacological benefits on a cluster of obesity-related metabolic complications when administered to preclinical models. This Review discusses FGF21 analogues and mimetics and highlights their efficacy in preclinical models and clinical trials. The challenges in developing FGF21-based therapeutics are also considered.

This Review outlines the latest understanding of the pathogenesis of primary aldosteronism. Current treatment options are also discussed, including the potential for targeted therapies.

This Review highlights the evidence from clinical trials that diet-induced weight loss interventions can be used to treat type 2 diabetes mellitus. The composition of the diet and the importance of physical exercise programmes are discussed. Lifestyle interventions for prevention of type 2 diabetes mellitus are also considered.

Most research treats endometriosis as a single entity, potentially obscuring informative subtype-specific associations with risk factors, biomarkers and treatment responses. A 2020 study raises the hypothesis that deep endometriosis oestrogen receptor-α expression might be associated with progestin treatment and the degree of post-surgical excision pain.

For type 1 diabetes mellitus (T1DM), keeping glucose levels within the normal range of 65–150 mg/dl with administered insulin has had limited success. Now, Fussenegger and colleagues have engineered cells to release insulin in response to electrical signals, but can this advance lead to better glucose control?

Thermogenic adipose tissue is a metabolic sink for excess fuel and is a promising target for the treatment of obesity and type 2 diabetes mellitus. However, hurdles exist in activating thermogenic adipose tissue in humans. A new study developed a drug screening platform utilizing human beige adipose tissue and identified non-canonical activators.

This Review highlights the beneficial adaptive responses to exercise in skeletal muscle and other tissues as well as their molecular mechanisms. In addition, the possibility of exercise-like therapeutic interventions is discussed, providing relevant examples that have used this approach.

This Review discusses the ways in which adult reproductive function can be shaped by childhood events and examines the evidence for the epigenetic regulation of key regulatory genes that govern the central control of reproduction.

Pre-eclampsia and fetal growth restriction are diseases of pregnancy that arise from disorders of placental development. This Review discusses healthy development of the placenta and considers disease mechanisms, biomarkers and diagnosis of pre-eclampsia and fetal growth restriction.

This Review highlights the research advances, advantages and challenges in several different strategies for generating functional β-cells for therapeutic use in diabetes mellitus. In addition, scalable bioengineering processes are also discussed for the realization of the therapeutic potential of derived β-cells.