Loudon, A. S. I. | Search bioRxiv

bioRxiv2020

Adipocyte REVERBα dictates adipose tissue expansion during obesity

The circadian clock component REVERB is considered a dominant regulator of lipid metabolism, with global Reverb deletion driving dysregulation of white adipose tissue (WAT) lipogenesis and obesity. However, a similar phenotype is not observed under adipocyte-selective deletion (ReverbFlox2-6AdipoCre), and transcriptional profiling demonstrates that, under basal conditions, direct targets of REVERB regulation are limited, and include the circadian clock and collagen dynamics. Under high-fat diet (HFD) feeding, ReverbFlox2-6AdipoCre mice do manifest profound obesity, yet without the accompanying WAT inflammation and fibrosis exhibited by controls. Integration of the WAT REVERB cistrome with differential gene expression reveals broad control of metabolic processes by REVERB which is unmasked in the obese state. Adipocyte REVERB does not drive an anticipatory daily rhythm in WAT lipogenesis, but rather modulates WAT activity in response to alterations in metabolic state. Importantly, REVERB action in adipocytes is critical to the development of obesity-related WAT pathology and insulin resistance.

physiology↗

bioRxiv2020

A single nuclei transcriptomic analysis of the Atlantic salmon gill through smoltification and seawater transfer

Anadromous salmonids begin life adapted to the freshwater environments of their natal streams before a developmental transition, known as smoltification, transforms them into marine-adapted fish. In the wild, the extending photoperiods of spring stimulates smoltification, typified by radical reprogramming of the gill from an ion-absorbing organ to ion-excreting organ. Prior work has highlighted the role of specialized "mitochondrion-rich" cells in delivering this phenotype. However, transcriptomic studies identify thousands of smoltification-driven differentially regulated genes, indicating that smoltification causes a multifaceted, multicellular change; but direct evidence of this is lacking. Here, we use single-nuclei RNAseq to characterize the Atlantic salmon gill during smoltification and seawater transfer. We identify 20 distinct clusters of nuclei, including known, but also novel gill cell types. These data allow us to isolate cluster-specific, smoltification-induced changes in gene expression. We also show how cellular make-up of the gill changes through smoltification. As expected, we noted an increase in the proportion of seawater mitochondrion-rich cells, however, we also identify a reduction of several immune-related cells. Overall, our results provide unrivaled detail of the cellular complexity in the gill and suggest that smoltification triggers unexpected immune reprogramming directly preceding seawater entry.

molecular biology↗