Holst reflects on the development of GLP-1-based drugs for the therapy of obesity, from early observations to remarkable results in more recent clinical trials, discussing physiological, pharmacological and clinical considerations related to their use.

This authoritative Perspective lays a foundation for the field of obesity research by comparing commonalities and differences between competing models of obesity pathogenesis and by defining terms that are at the core of this discussion.

This Review provides an overview of the interplay between host diet and the gut microbiota, and how this affects brain function.

Veniant et al. report here on a GIPR antagonist conjugated to GLP-1 analogues that reduces body weight and improves metabolic markers in preclinical and phase 1 clinical settings.

The authors identify feimin as a feeding-induced myokine that regulates glucose homeostasis via the MERTK–AKT signalling axis in mice and humans.

The authors uncover the role of cellular Feimin in regulating exercise performance by modulating SLN-mediated muscle thermogenesis.

By increasing NAD⁺ consumption in various organelles, mitochondria are revealed to act as buffers that help maintain subcellular NAD⁺ levels. At the same time, cells are found to be particularly sensitive to a decline in NAD⁺ levels originating from mitochondria themselves.

Sellers, van Beek and colleagues show that intermittent cold exposure for 10 days, which induced 1 h of shivering per day, improves glucose homeostasis, lipid metabolism and blood pressure in adults with overweight or obesity.

Combining rabies-based connectomics with single-nucleus transcriptomics, the authors identify a neural circuit through which GLP-1 receptor agonists suppress appetite in mice.

Nam et al. show that limited glucose availability similar to the tumour microenvironment confers resistance against chemotherapeutic drugs that target DNA synthesis.

Here, we introduce Artificial Intelligence Ready and Equitable Atlas for Diabetes Insights (AI-READI), a multidisciplinary data-generation project designed to create and share a multimodal dataset optimized for artificial intelligence research in type 2 diabetes mellitus.

We have lost a distinguished scientist who made indelible contributions to our knowledge of exercise physiology and diabetes and was an advocate for mentoring and transparency in research.

Although Western societies are mesmerized by the power of new anti-obesity drugs, we must not forget how diet can affect metabolic outcomes. In this Focus issue, and accompanying web collection, we showcase a series of Reviews, Comments and original research articles that present up-to-date evidence on how dietary interventions can affect cardiometabolic health.

Extracellular vesicles (EVs) are now recognized as powerful modulators of metabolism, and thus the new field of EV-mediated metabolic regulation is growing exponentially. Here, we discuss special experimental considerations for the study of EV function in metabolism.

Despite the high utility and widespread use of Cre driver lines, lack of Cre specificity, Cre-induced toxicity or poor experimental design can affect experimental results and conclusions. Such pitfalls must be considered before embarking on any Cre-based studies in metabolic research.