Reviews & Analysis

This study shows that a 10% weight loss induced by calorie restriction and multimodal exercise training results in a much greater increase in whole-body insulin sensitivity than matched weight loss induced by calorie restriction alone. This result underscores the importance of adding regular exercise to a weight loss programme, as it improves metabolic health.

Time-restricted eating, a form of intermittent fasting, has shown promise in promoting metabolic health. In mice, limiting food accessibility only to the active cycle reduces body weight and improves glucose homeostasis; now, Xin et al. show that restricting feeding to the resting period increases their running performance.

This study reveals that oxidative aneuploid cancer cells exhibit an upsurge of NADPH levels during mitosis, which neutralizes excessive reactive oxygen species and protects against chromosome mis-segregation.

How photosynthetic microbes regulate CO₂ fixation and carbon metabolism in response to fluctuating environments is of fundamental and industrial relevance. In this issue, Lu et al. uncover a cryptic enzymatic function that accelerates the shutdown of the Calvin cycle under a transition into the dark.

Adipogenesis of adipose progenitor cells is considered metabolically beneficial. Two laboratories have simultaneously discovered that adipose progenitors also give rise to structural WNT-regulated adipose tissue-resident (SWAT) cells during adipogenesis to maintain the progenitor pool.

An elegant quantitative analysis of brown fat and skeletal muscle metabolite flux reveals unpredicted fuel usage during thermogenesis, which suggests that brown fat predominantly uses glucose and lactate and acts as a nitrogen scavenger.

Many people with obesity and type 2 diabetes achieve remission of their diabetes after Roux-en-Y gastric bypass surgery, but the mechanisms of remission remain disputed. We provide our perspective on competing datasets that point towards this effect being due either entirely to the loss of weight or to weight loss-independent effects.

This Perspective provides a concise overview of the diverse functions of vitamin K in physiology and metabolism, including its recently discovered role in ferroptosis.

Inflammation is characterized by cell metabolic reprogramming that can influence the outcome of metabolic syndrome-related diseases such as non-alcoholic fatty liver disease (NAFLD). In this issue, Weiss et al. discover that preventing the production of the immunomodulatory metabolite itaconate increases liver fat accumulation in mouse models of NAFLD and that treatment with itaconate may promote fat oxidation. This study reveals new therapeutic potential for targeting the itaconate metabolic pathway in NAFLD.

Post-ingestive signals of nutrient availability can drive food reward and neural responses independently of orosensory signals. van Galen et al. demonstrate that brain responses to these post-ingestive signals are impaired in people with obesity

This Perspective summarizes the development and clinical efficacy of gut hormone co-agonists for the treatment of diabetes and obesity.

Comparative metabolomic analyses of the guts of healthy colonized versus germ-free mice helped map microbial metabolites across the various intestinal niches. The microbial origin and biochemical processes underlying several metabolites could be inferred, even in areas difficult to access, such as the small intestine.

Functional genomic analyses reveal a complex relationship between the COBLL1 gene and metabolic health, as well as how the same variant can both reduce body fat and increase the risk of type 2 diabetes.

How mammals enter hypometabolic states, known as torpor and hibernation, has fascinated researchers for decades, but the central control mechanisms that regulate entry into torpor have surfaced only recently. Yang and colleagues demonstrate that torpor-like hypometabolic states can be induced non-invasively by ultrasound, providing new routes for exploiting the underlying mechanisms and biomedical applications of this process in the future.

M⁶A RNA modifications mediate RNA processing and stability. Ceramides are lipid metabolites containing an amino acid-based backbone, which promote metabolic dysfunction. Wang et al. describe a novel m⁶A-dependent regulatory node that tunes ceramide-generating enzymes.

Glycolysis provides building blocks for the proinflammatory activation of macrophages and simultaneously generates pyruvate. In this issue of Nature Metabolism, Ran et al. provide evidence that the transport of pyruvate to fuel the Krebs cycle in the mitochondria is not required in the inflammatory response.

Most of human microbiome research has focused on analysing faecal samples, which represent the final stop of the digestive journey. Two recent articles use a novel sampling approach to capture luminal content at different points during digestion and reveal that the analysis of faecal samples tells only a fraction of the story.

In this issue of Nature Metabolism, a gut bacterial glucosidase that degrades the antidiabetic drug acarbose is linked to poor treatment response. Its widespread distribution in the human microbiome could compromise the efficacy of acarbose treatment in many patients.

In this instalment of Career pathways, we hear from Gerta Hoxhaj and Ed Reznik about how they followed their passion for science, the value of collaborations and mentors, asking big questions and how to think differently about metabolism.

Kim and colleagues discuss the regulatory mechanisms of lipogenesis, the physiological and pathological role of lipogenesis in tissues such as adipose tissue, liver, neurons and cancer, and how lipogenesis may be targeted therapeutically to ameliorate disease.