eLife-Directing visceral white adipocyte precursors to a thermogenic adipocyte fate improves insulin sensitivity in obese mice.pdf
journal contributionposted on 04.03.2019, 22:01 authored by Chelsea Hepler, Mengle Shao, Jonathan Xia, Alexandra Ghaben, Mackenzie Pearson, Lavanya Vishvanath, Ankit Sharma, Thomas Morley, William Holland, Rana Gupta
Visceral adiposity confers significant risk for developing metabolic disease in obesity
whereas preferential expansion of subcutaneous white adipose tissue (WAT) appears protective.
Unlike subcutaneous WAT, visceral WAT is resistant to adopting a protective thermogenic
phenotype characterized by the accumulation of Ucp1+ beige/BRITE adipocytes (termed
‘browning’). In this study, we investigated the physiological consequences of browning murine
visceral WAT by selective genetic ablation of Zfp423, a transcriptional suppressor of the adipocyte
thermogenic program. Zfp423 deletion in fetal visceral adipose precursors (Zfp423loxP/loxP; Wt1-
Cre), or adult visceral white adipose precursors (PdgfrbrtTA; TRE-Cre; Zfp423loxP/loxP), results in the
accumulation of beige-like thermogenic adipocytes within multiple visceral adipose depots.
Thermogenic visceral WAT improves cold tolerance and prevents and reverses insulin resistance in
obesity. These data indicate that beneficial visceral WAT browning can be engineered by directing
visceral white adipocyte precursors to a thermogenic adipocyte fate, and suggest a novel strategy
to combat insulin resistance in obesity.