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.

Nshanian et al. investigate the differential effects of the short-chain fatty acids propionate and butyrate on chromatin remodelling and gain insight into the mechanisms that drive selective histone acylation.

Intestinal TM6SF2 is found to interact with fatty acid-binding protein 5 to modulate the secretion of fatty acids and the composition of the gut microbiota, thereby protecting against metabolic dysfunction-associated steatohepatitis.

During liver damage repair, the circadian clock in the liver is shown to act together with HIF-1α signalling to regulate pentose phosphate pathway activity and nucleotide availability.

Palme et al. investigate the fundamental principles that enable metabolic flux sensing in yeast.

Kern Coquillat et al. show that NK cells rely on exogenous pyruvate import to support effector functions.

Under low-protein conditions, decrease of protein NUFIP1 is found to impair DNA damage response and induce necroptosis in the intestine, thereby contributing to intestinal inflammation in male mice with inflammatory bowel disease.

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.