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

• DOI: 10.1038/s42255-019-0101-4
• Publication Date: 2019-08-19T16:02:55Z
• Authors: Jasper M. A. de Jong; Wenfei Sun; Nuno D. Pires; Andrea Frontini; Miroslav Balaz; Naja Z. Jespersen; Amir Feizi; Katarina Petrovic; Alexander W. Fischer; Muhammad Hamza Bo...; Tarja Niemi; Pirjo Nuutila; Saverio Cinti; Søren Nielsen; Camilla Scheele; Kirsi Virtanen; Barbara Cannon; Jan Nedergaard; Christian Wolfrum; Natasa Petrovic
• Keywords: 2. Zero hunger; 0301 basic medicine; 570; Mice; 03 medical and health sciences; Adipose Tissue, Brown; ta1184; ta1182; 610; Animals; Humans; Thermogenesis

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.