Research articles

Hypothalamic melanocortin neurons control energy homoeostasis by modulating appetite. Here, the authors reveal a role for the transcription factor Tbx3 as a regulator of the peptidergic identity and function of immature and mature mouse melanocortin neurons.

Bone marrow-derived cells can rapidly enter the systemic circulation, but how this is achieved is unclear. Grüneboom et al. identify tiny capillaries, termed trans-cortical vessels (TCVs), that connect the bone marrow cavity to the systemic vasculature, and show that the majority of blood in long bones passes through TCVs.

Perineuronal nets (PNNs) are extracellular matrix structures that have been linked to neuronal plasticity in the cortex and hippocampus. Here, the authors report the existence of PNN-like structures in a key region regulating energy homoeostasis, the hypothalamic arcuate nucleus, and show that PNN formation in this area early in life is influenced by the hormone leptin.

ACC1 is a rate-limiting enzyme during fatty acid biosynthesis. Here the authors describe how loss of ACC1 enhances CD4⁺ memory T cell formation and improves outcome in a murine model of parasite infection, indicating that lipid biosynthesis directs cell-fate determination during the generation of memory T cells.

As opposed to circulating factors that promote energy expenditure, hormones that suppress energy expenditure have remained largely elusive. Here, Wang et al. show that the hepatokine Tsukushi is upregulated in obesity and inhibits sympathetic activity and thermogenesis in fat by promoting whitening.

Ageing is associated with deteriorating immune function and metabolic diseases. Here, the authors show that plasma levels of the stress-response protein MANF decline with age in various organisms and that MANF has beneficial effects on immune and metabolic function, particularly in the liver, in old mice.

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.

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.

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.