Volume 1 Issue 2, February 2019

Hypothalamic neuronal diversity is at the core of whole-body energy-homeostasis control, but the molecular mechanisms governing neuronal neuropeptide specification remain incompletely understood. A new study in Nature Metabolism adds a relevant piece to the puzzle of how key hypothalamic neuronal populations maintain their peptidergic identity throughout the lifespan.

Like stem cells, cancer cells can rapidly proliferate but, unlike stem cells, they are mostly locked into a malignant identity. Here, Finley and Intlekofer highlight commonalities in anabolic pathways that support proliferation in cancer and stem cells, and point out unique metabolic features that influence self-renewal and differentiation.

Adipose tissue responds to a variety of hormonal and environmental cues with changes in size, cellular composition and metabolic activity. Here Kajimura and Chouchani review our current understanding of adipocyte metabolism in physiology and metabolic disease, and they discuss strategies to reprogram adipocyte fate and metabolism.

Neurons and astrocytes cooperate metabolically but differ in key aspects of their metabolism, including the production of mitochondrial reactive oxygen species (ROS). Here, the authors show that mitochondrial ROS produced in astrocytes affect neuronal metabolism and mouse memory and behaviour.

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.

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.

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.

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.

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.

Many beneficial effects of exercise are mediated by factors secreted from the exercising muscle, so-called myokines. Here, the authors identify what might be the first exercised-induced adipokine, TGF-β2, which is secreted from subcutaneous fat in response to exercise-induced increases in serum lactate levels and has beneficial metabolic effects in mice.