eLife-Directing visceral white adipocyte precursors to a thermogenic adipocyte fate improves insulin sensitivity in obese mice.pdf

<div>Visceral adiposity confers significant risk for developing metabolic disease in obesity</div><div>whereas preferential expansion of subcutaneous white adipose tissue (WAT) appears protective.</div><div>Unlike subcutaneous WAT, visceral WAT is resistant to adopting a protective thermogenic</div><div>phenotype characterized by the accumulation of Ucp1+ beige/BRITE adipocytes (termed</div><div>‘browning’). In this study, we investigated the physiological consequences of browning murine</div><div>visceral WAT by selective genetic ablation of Zfp423, a transcriptional suppressor of the adipocyte</div><div>thermogenic program. Zfp423 deletion in fetal visceral adipose precursors (Zfp423loxP/loxP; Wt1-</div><div>Cre), or adult visceral white adipose precursors (PdgfrbrtTA; TRE-Cre; Zfp423loxP/loxP), results in the</div><div>accumulation of beige-like thermogenic adipocytes within multiple visceral adipose depots.</div><div>Thermogenic visceral WAT improves cold tolerance and prevents and reverses insulin resistance in</div><div>obesity. These data indicate that beneficial visceral WAT browning can be engineered by directing</div><div>visceral white adipocyte precursors to a thermogenic adipocyte fate, and suggest a novel strategy</div><div>to combat insulin resistance in obesity.</div>