Human Brown Adipose Tissue Is Phenocopied by Classical Brown Adipose Tissue in Physiologically Humanized Mice

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 (approx. 30 °C) and to an energy-rich (high fat, high sugar) diet. We find that morphological, cellular and molecular characteristics (both marker gene expression 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 argue 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.