Human brown adipose tissue is phenocopied by classical brown adipose tissue in physiologically humanized mice

Nature Metabolism
Jasper M A de JongNatasa Petrovic

Abstract

Human and rodent brown adipose tissues (BAT) appear morphologically and molecularly different. Here we compare human BAT with both classical brown and brite/beige adipose tissues of 'physiologically humanized' mice: middle-aged mice living under conditions approaching human thermal and nutritional conditions, that is, prolonged exposure to thermoneutral temperature (approximately 30 °C) and to an energy-rich (high-fat, high-sugar) diet. We find that the morphological, cellular and molecular characteristics (both marker and adipose-selective gene expression) of classical brown fat, but not of brite/beige fat, of these physiologically humanized mice are notably similar to human BAT. We also demonstrate, both in silico and experimentally, that in physiologically humanized mice only classical BAT possesses a high thermogenic potential. These observations suggest that classical rodent BAT is the tissue of choice for translational studies aimed at recruiting human BAT to counteract the development of obesity and its comorbidities.

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Datasets Mentioned

BETA
PRJEB20634
E-MTAB-7561
E-MTAB-7565

Methods Mentioned

BETA
RNA-Seq
PCA
biopsies
PCR
biopsy
electrophoresis

Software Mentioned

Subread package
TruSeq3
biomaRt
QoRTs
Trimmomatic
Biopython
Ensembl
PROFAT
DESeq2
R

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