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MacDonald and Rorsman discuss the physiological role of glucagon, regulation and dysregulation of its secretion from alpha cells, and the potential of glucagon as a therapeutic target for diabetes and associated metabolic diseases.
Sepsis takes a severe toll in the heart and can in some instances induce irreversible dysfunction. Zhang et al. discover a subset of macrophages that protects the septic heart by removing inflammogenic material released by cardiomyocytes.
Human pluripotent stem cell-derived pancreatic islets (PSC-islets) hold promise in type I diabetes treatment, although their delivery is a challenge. We describe a new abdominal infusion transplantation protocol that enables the survival, maturation and maintenance of functional PSC-islets in diabetic monkeys.
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.
Multiomic analyses in an individual with severe, early-onset obesity, followed by targeted screening in additional patients identifies a tandem duplication at the ASIP gene (encoding agouti-signalling protein) as a novel cause of monogenic obesity, with implications for genetic diagnosis of obesity.
mTORC1 integrates environmental signals to promote anabolism and repress catabolism. In this issue of Nature Metabolism, Hosios et al. identify a role for mTORC1 in controlling endosomal trafficking and degradation of membrane phospholipids in the lysosome, revealing a novel process used by cells to adapt to poor growth conditions.
The physiological role of aerobic glycolysis (also known as the Warburg effect), which is observed in many tumours, is still not fully understood. The finding that lactate dehydrogenase A (LDHA) activates RAC1 in breast cancer sheds new light on this persistently enigmatic aspect of cancer metabolism.
Mitochondria of young adipocytes release RNA molecules that serve as signals to stimulate the transcription of nuclear-encoded genes for mitobiogenesis and thermogenesis. Mitochondrial RNA (mtRNA) efflux thus establishes retrograde mitochondria–nucleus signalling and triggers heat production from fat. Stimulating this signalling protects against obesity in mice.
Sustained weight loss and weight maintenance are key challenges for the treatment of obesity. Here, the authors show that a high-protein diet following weight loss can protect against weight regain, through a process dependent on the gut microbiome.
A maternal high-fat diet (mHFD) alters behavior in offspring in a sex-specific manner. We demonstrate that mHFD increases endotoxin levels in fetal tissues and decreases long-term serotonin bioavailability in male offspring owing to removal of serotonin neurons by microglia in the embryonic brain.
BCAA homeostasis is crucial to human health. A new study demonstrates that a mitochondrial metabolon assembled by BCAT2 and BCKDH controls BCAA metabolism in vivo, providing opportunities to develop strategies for repairing dysfunctional BCAA homeostasis.
Innate lymphoid cells (ILCs) are an integral part of the innate immune system. This Review discusses how ILC function is regulated by both intrinsic and extrinsic metabolic pathways, and how ILCs contribute to metabolic disease.
Adipose tissue is a specialized connective tissue and a major endocrine organ. Brown adipose tissue (BAT) secretes factors that modulate whole-body metabolic homeostasis and can affect distant organs. The discovery that BAT-secreted neuregulin 4 influences atherosclerotic progression opens new opportunities for treating atherosclerosis.
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 immune-modulatory metabolite itaconate is secreted by myeloid-derived suppressor cells and taken up by CD8+ T cells to suppress their proliferation and function. In mice, blocking itaconate production enhances the efficacy of immune checkpoint blockade.
The human gut microbiome metabolizes hundreds of drugs, but the clinical relevance of these biotransformations remains unclear. Chen and colleagues show that gut bacterial nicotine metabolism protects against liver disease.
Scherer and colleagues demonstrate that manipulation of iron concentrations in the mitochondrial matrix of macrophages has profound effects on their polarization, leading to concomitant changes in adipocyte iron concentrations and, ultimately, systemic metabolic effects.
The core metabolic pathways are tightly intertwined, creating challenges for metabolic engineering. Yu et al. present a synthetic decarboxylation cycle that substitutes the TCA cycle in energy metabolism, gaining high yields in the production of reduced compounds such as fatty acids.
