Comparative transcriptomic analysis of rabbit interscapular brown adipose tissue whitening under physiological conditions

Abstract

Interscapular brown adipose tissue (iBAT) of both rabbits and humans exhibits a similar whitening phenomenon under physiological conditions. However, a detailed characterization of iBAT whitening in them is still lacking. Here, we chose rabbits as a model to gain a better understanding of the molecular signature changes during the whitening process of iBAT by transcriptomic analysis of rabbit iBAT at day 1, day 14, 1 month and 4 months after birth. We applied non-invasive MRI imaging to monitor the whitening process and correlated these changes with analysis of morphological, histological and molecular features. Principal component analysis (PCA) of differentially expressed genes delineated three major phases for the whitening process as Brown, Transition and Whitened BAT phases. RNA-sequencing data revealed that whitening of iBAT was an orchestrated process where multiple types of cells and tissues participated in a variety of physiological processes including neovascularization, formation of new nervous networks and immune regulation. Several key metabolic and signalling pathways contributed to whitening of iBAT, and immune cells and immune regulation appeared to play an overarching role.

Quantitative assessment of brown adipose tissue whitening in a high-fat-diet murine model using synthetic magnetic resonance imaging

“…Adipose tissue is a highly plastic and dynamic tissue [ 24 ]. The plasticity of BAT and WAT determines whether an individual phenotype is obese or thin [ 25 ].…”

“…The plasticity of BAT and WAT determines whether an individual phenotype is obese or thin [ 25 ]. The metabolism, structure, and phenotype of adipose tissue can have significant changes under various physiological and pathological conditions [ 24 , 25 ]. WAT can acquire a brown-like phenotype by various stimuli, such as cold exposure and β-adrenergic receptor agonists, this progress is called browning [ [24] , [25] , [26] , [27] ].…”

“…The metabolism, structure, and phenotype of adipose tissue can have significant changes under various physiological and pathological conditions [ 24 , 25 ]. WAT can acquire a brown-like phenotype by various stimuli, such as cold exposure and β-adrenergic receptor agonists, this progress is called browning [ [24] , [25] , [26] , [27] ]. BAT whitening induced by various interventions, such as HFD and chronic glucocorticoid exposure can lead to obesity and insulin resistance [ 1 , 4 , 9 , 28 ].…”

Progress and obstacles in transplantation of brown adipose tissue or engineered cells with thermogenic potential for metabolic benefits

“…In molecular biology, the gene expression pattern of whitening BAT might show upregulated inflammasome activation, ER stress markers, and a deficiency in markers of vascularization,b-adrenergic signaling, electron transport chain, rate-limiting enzymes regulating substrate breakdown, specific membrane receptors, etc. (38)(39)(40).…”