Perspectives

Nicholls and Brand present a bioenergetic critique of the futile creatine cycle as a mechanism for UCP1-independent diet-induced thermogenesis in brown adipose tissue.

In this Perspective, the authors discuss the various mouse preclinical models that are available for the study of non-alcoholic steatohepatitis (NASH) and NASH-induced hepatocellular carcinoma, and provide advice on reporting practices and how to select the most appropriate model.

The authors of this Perspective discuss the remarkable plasticity of the intestine in response to dietary and physiological changes, and highlight the importance of intestinal remodelling and metabolism in maintaining energy balance of the organism.

The authors of this Perspective summarize the state of human islet research and compare available islet procurement methods, proposing strategies to increase collaboration and standardization to accelerate discoveries on diabetes.

In this Perspective, Pekkurnaz and Wang offer an integrative overview on how mitochondrial homeostasis and diversity in morphology, distribution, composition and function contribute to meeting specific cellular demands, with a special focus on neurons

This Perspective summarizes the ongoing development of CAR-based therapies in indications beyond cancer, including for cardiometabolic diseases, fibrosis, autoimmune diseases and ageing.

Interleukin 6 is a pleiotropic cytokine that can be pro- or anti-inflammatory, depending on the metabolic context. Kistner et al. propose that these context-dependent effects are due to its adaptive role for short-term energy allocation, particularly during physical activity.

Bartman et al. provide a detailed review of techniques for measuring metabolic fluxes in intact mammals, how to analyse and interpret the results and how these techniques can be applied to investigate metabolism in vivo.

Quarta et al. discuss POMC neuronal heterogeneity and how specific subpopulations of POMC neurons can have diverse effects on appetite, whole-body metabolic physiology and the development of obesity.

Van Gastel and Carmeliet provide an overview of emerging findings on how cellular metabolism shapes skeletal stem cell fate and function, and discuss how metabolic dysregulation might contribute to skeletal ageing and degenerative diseases.

Zhang et al. discuss insights into the genetics of extreme human longevity and how genetics knowledge can be harnessed to guide the development of new therapies to extend human healthspan.

Enerbäck and Rabinowitz summarize emerging evidence that lactate serves as a universal circulating fuel for mammalian cells.

The importance of metabolism in the course of SARS-Cov-2 infection is highlighted by the metabolic comorbidities of COVID-19. In this Perspective, Ayres provides insight into how current knowledge of immunometabolism and metabolic diseases can inform the understanding of COVID-19 pathology, and proposes potential metabolism-based clinical solutions.

He et al. highlight the potential, and some of the drawbacks, of applying single-cell analyses in ageing research.

Activation of tissue-resident myeloid cells in the brain, known as microglia, is thought to drive obesity-associated hypothalamic dysfunction. The authors of this Perspective present a more nuanced view of microglia, echoing lessons learned from the field of adipose macrophage biology: instead of simply responding to diet-induced damage, microglia are proposed to act as nutrient and environmental sensors that regulate hypothalamic physiology, a role that, if hijacked by chronic overnutrition, can produce disease.