bims-mimbat 2024-09-01 papers

Issue of 2024‒09‒01
two papers selected by
José Carlos de Lima-Júnior, Washington University

Cell Metab. 2024 Aug 13. pii: S1550-4131(24)00326-7. [Epub ahead of print]

Mitochondrial membrane lipids in the regulation of bioenergetic flux.

Oxidative phosphorylation (OXPHOS) occurs through and across the inner mitochondrial membrane (IMM). Mitochondrial membranes contain a distinct lipid composition, aided by lipid biosynthetic machinery localized in the IMM and class-specific lipid transporters that limit lipid traffic in and out of mitochondria. This unique lipid composition appears to be essential for functions of mitochondria, particularly OXPHOS, by its effects on direct lipid-to-protein interactions, membrane properties, and cristae ultrastructure. This review highlights the biological significance of mitochondrial lipids, with a particular spotlight on the role of lipids in mitochondrial bioenergetics. We describe pathways for the biosynthesis of mitochondrial lipids and provide evidence for their roles in physiology, their implications in human disease, and the mechanisms by which they regulate mitochondrial bioenergetics.

Keywords: bioenergetics; mitochondria; phospholipids

DOI: https://doi.org/10.1016/j.cmet.2024.07.024

Nature. 2024 Aug 28.

Sympathetic neuropeptide Y protects from obesity by sustaining thermogenic fat.

Yitao Zhu, Lu Yao, Ana L Gallo-Ferraz, Bruna Bombassaro, Marcela R Simões, Ichitaro Abe, Jing Chen, Gitalee Sarker, Alessandro Ciccarelli, Linna Zhou, Carl Lee, Davi Sidarta-Oliveira, Noelia Martínez-Sánchez, Michael L Dustin, Cheng Zhan, Tamas L Horvath, Licio A Velloso, Shingo Kajimura, Ana I Domingos.

Human mutations in neuropeptide Y (NPY) have been linked to high body mass index but not altered dietary patterns1. Here we uncover the mechanism by which NPY in sympathetic neurons2,3 protects from obesity. Imaging of cleared mouse brown and white adipose tissue (BAT and WAT, respectively) established that NPY+ sympathetic axons are a smaller subset that mostly maps to the perivasculature; analysis of single-cell RNA sequencing datasets identified mural cells as the main NPY-responsive cells in adipose tissues. We show that NPY sustains the proliferation of mural cells, which are a source of thermogenic adipocytes in both BAT and WAT4-6. We found that diet-induced obesity leads to neuropathy of NPY+ axons and concomitant depletion of mural cells. This defect was replicated in mice with NPY abrogated from sympathetic neurons. The loss of NPY in sympathetic neurons whitened interscapular BAT, reducing its thermogenic ability and decreasing energy expenditure before the onset of obesity. It also caused adult-onset obesity of mice fed on a regular chow diet and rendered them more susceptible to diet-induced obesity without increasing food consumption. Our results indicate that, relative to central NPY, peripheral NPY produced by sympathetic nerves has the opposite effect on body weight by sustaining energy expenditure independently of food intake.

DOI: https://doi.org/10.1038/s41586-024-07863-6