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The growth of new blood vessels (angiogenesis) is a bio-energetically demanding process. Surprisingly, the specific role of mitochondria in angiogenesis remains unclear. A study in this issue of Nature Metabolism now demonstrates that mitochondrial respiration is essential for angiogenic growth by controlling endothelial proliferation.

Extracellular matrix (ECM) homeostasis is essential for normal tissue function, and its perturbation by injury, trauma or disease results in fibrosis. Here, the authors show that glycolysis and the fatty acid oxidation pathway regulate fibroblast behaviour and have reciprocal effects in ECM upregulation and downregulation, respectively.

Despite the similarity of metabolic flux patterns in different organisms, the underlying governing principles remain unclear. Using a constraint-based thermodynamic–stoichiometric model as well as quantitative metabolome and physiological data, Niebel et al. identify an upper limit on the cellular Gibbs energy dissipation rate, which could shape metabolism across organisms.

Nicotinamide mononucleotide (NMN) is a biosynthetic precursor of NAD⁺, but how NMN is taken up into cells has not been entirely clear. Here the authors discover a specific NMN transporter, encoded by the Slc12a8 gene, which regulates NMN uptake and cellular NAD⁺ levels in vitro and in the mouse intestine in vivo.

The gut microbiome has emerged as an important regulator of host physiology and disease, including metabolic diseases. Here Cani et al. provide a broad overview of mechanisms through which the gut microbiota affects metabolic regulation in the host.

Transferrin receptor 2 (Trf2) is known to regulate iron homeostasis through its action in the liver. Here the authors report a previously unrecognised role of Trf2 in regulating bone homeostasis mediated by modulation of BMP signalling specifically on osteoblasts.

Endothelial cells (ECs) require glycolysis during angiogenesis; however, the function of the mitochondrial respiratory chain during this process is unclear. Here the authors show that mitochondrial respiration in ECs is required for angiogenesis as the biosynthetic role of mitochondria is needed for EC proliferation.

Intermediate metabolites of the Krebs cycle serve bioenergetic and biosynthetic needs but have recently also been linked to signalling. The authors of this Review summarize such non-metabolic signalling functions of succinate, fumarate, itaconate, 2-hydroxyglutarate isomers and acetyl-CoA in both immune cells and cancer cells.

Cholesterol accumulation in cells and blood vessels promotes the development of vascular diseases. The long non-coding RNA CHROME can help clear excess cholesterol and provide protection from atherosclerosis.

Maintenance of cholesterol homeostasis is essential to human health. Here, the authors identify and characterize a primate-specific long noncoding RNA, called CHROME, that controls cholesterol homeostasis through fine-tuning of miRNAs and whose levels are elevated in human atherosclerosis.

Impaired adipocyte insulin signalling characterizes insulin resistance. Here the authors show that the hormone-sensitive lipase can sequester the glucose-responsive transcription factor ChREBP in the cytoplasm, which prevents transcription of its target ELOVL6, resulting in reduced insulin signalling.

The metabolic dependencies of androgen receptor (AR)-driven growth in prostate adenocarcinoma are largely unknown but could represent a therapeutic target when hormonal manipulations fail. Here the authors demonstrate that the mitochondrial pyruvate carrier (MPC) is transcriptionally regulated by AR and that MPC inhibition suppresses tumour growth in hormone-responsive and castrate-resistant conditions.

Obese and dysfunctional adipose tissue is known to be hypoxic. Here the authors show that adipocyte oxygen consumption increases early after onset of high-fat diet feeding owing to activation of the mitochondrial protein ANT2 and that specific inhibition of ANT2 reduces adipose tissue hypoxia, inflammation and insulin resistance.

Glucose-dependent insulinotropic polypeptide (GIP) is a gut incretin hormone released in response to nutrients. Here, the authors report an anti-inflammatory and antiobesogenic mechanism of GIP by showing that loss of GIP receptor signalling in myeloid cells promotes pro-inflammatory S100A8/A9 release in adipose tissue.