Cold‐inducible lncRNA266 promotes browning and the thermogenic program in white adipose tissue

Abstract Cold‐induced nonshivering thermogenesis has contributed to the improvement of several metabolic syndromes caused by obesity. Several long noncoding RNAs (lncRNAs) have been shown to play a role in brown fat biogenesis and thermogenesis. Here we show that the lncRNA lnc266 is induced by cold exposure in inguinal white adipose tissue (iWAT). In vitro functional studies reveal that lnc266 promotes brown adipocyte differentiation and thermogenic gene expression. At room temperature, lnc266 has no effects on white fat browning and systemic energy consumption. However, in a cold environment, lnc266 promotes white fat browning and thermogenic gene expression in obese mice. Moreover, lnc266 increases core body temperature and reduces body weight gain. Mechanistically, lnc266 does not directly regulate Ucp1 expression. Instead, lnc266 sponges miR‐16‐1‐3p and thus abolishes the repression of miR‐16‐1‐3p on Ucp1 expression. As a result, lnc266 promotes preadipocyte differentiation toward brown‐like adipocytes and stimulates thermogenic gene expression. Overall, lnc266 is a cold‐inducible lncRNA in iWAT, with a key role in white fat browning and the thermogenic program.