Articles in 2021

Immune cells can promote the thermogenic phenotype of white adipocytes during cold exposure, in a process known as ‘browning’ or ‘beiging’. Wang et al. now reveal a potential mechanism whereby alternatively activated macrophages prompt adipose sympathetic nerve fibres to release norepinephrine and promote adipocyte beiging.

Slit3 is shown to be secreted from M2-like macrophages resident in adipose tissue, where it enables cold adaptation by stimulating norepinephrine release from sympathetic neurons.

Discovering that a different lab has reached similar findings to yours before publishing can be frustrating. But it does not have to be. Communication between labs might be the best way forward.

Alterations to the extracellular matrix have long been associated with cancer progression and therapeutic resistance. Schwörer et al. describe a mechanism whereby fibroblasts reroute metabolites to fuel the demands of collagen synthesis, leading to cancer progression.

The aberrant production of collagen by fibroblasts influences cancer progression. TCA cycle anaplerosis determines collagen production through pyruvate carboxylase, which could be targeted to inhibit tumour desmoplasia.

Ritchie et al. use polygenic scores to identify plasma proteins with causal roles in cardiometabolic disease.

Regulation of lipid metabolism by Hedgehog signalling is found to be mediated by a long non-coding RNA, named Hilnc, which can enhance Pparγ mRNA stability via the mRNA-binding protein IGF2BP2, and thereby affect obesity and liver steatosis.

A recent study shows how hyperinsulinaemia in obesity unexpectedly activates the cell cycle of overworked mature adipocytes in a process known as endo-reduplication, which represents a ‘last gasp’ strategy to remain functionally competent. However, this strategy fails and triggers premature senescence and tissue dysfunction.

Chella Krishnan et al. demonstrate sex-specific regulation of adipose tissue mitochondrial function that contributes to sex differences in susceptibility to metabolic syndrome traits.

Incorporating one-carbon molecules into metabolic engineering has involved altering central metabolism, which must overcome metabolic regulation. Developing one-carbon metabolic pathways that are orthogonal to central metabolism offers a promising alternative for bioproduct synthesis. Here, Chou, Lee, Zhu et al. describe an orthogonal pathway that has the potential for bioproduct synthesis from one-carbon molecules and can be independent of central metabolism.

Small extracellular vesicles (SEVs) can be used for the selective delivery of therapeutic agents from the blood to the brain. Milbank et al. make use of SEVs to selectively target neurons in the ventromedial hypothalamus of mice, extending this exciting approach to potential applications for the treatment of obesity.

Chou, Lee and Zhu et al. describe a synthetic metabolic pathway for C1 compound utilization using formate, formaldehyde and methanol as substrates.

Milbank et al. show that specific targeting of AMPKα1 in SF1 neurons of the VMH through systemic injection of small extracellular vesicles causes weight loss via increased brown adipose tissue thermogenesis.

In this study, the serine biosynthetic enzyme PHGDH is shown to transition from the cytosol to the nucleus following nutrient stress. Nuclear PHGDH reduces local NAD⁺ availability needed for the PARylation of the transcription factor c-Jun. Consequently, c-Jun activity is reduced, contributing to sustained cancer cell proliferation.

Pak et al. show that prolonged fasting is required for the effects of calorie restriction on insulin sensitivity, fuel utilization and ageing in mice.

Wiley and Campisi discuss metabolic inducers of senescence and alterations in cellular metabolism associated with senescence, while pointing out interventions that target metabolic processes to mitigate senescence.

Ma et al. find that PHGDH, which catalyses serine metabolism in the cytoplasm, transits to the nucleus during nutrient stress, where it promotes cell growth and tumorigenesis.

Syt7-dependent pancreatic insulin release is shown to be mediated by 5-IP₇ in response to parasympathetic stimulation of the GPCR M3R.

Dysfunctional efferocytosis impairs clearance of apoptotic cells in disease. A new study shows that glutamine catabolism supports efficient apoptotic cell efferocytosis via non-canonical glutamine transamination but not canonical GLUD1-dependent α-ketoglutarate production, in a process that may operate in human atherosclerosis.

The fasting-mimicking diet is a five-day cycle of near total fasting each month that extends healthspan in male mice. In this issue of Nature Metabolism, Mishra et al. demonstrate life-extending and cardioprotective benefits of the fasting-mimicking diet in middle-aged female mice that are consuming a high-fat diet.