[PDF][PDF] Enhanced leptin-stimulated Pi3k activation in the CNS promotes white adipose tissue transdifferentiation

L Plum, E Rother, H Münzberg, FT Wunderlich… - Cell metabolism, 2007 - cell.com
L Plum, E Rother, H Münzberg, FT Wunderlich, DA Morgan, B Hampel, M Shanabrough…
Cell metabolism, 2007cell.com
The contribution of different leptin-induced signaling pathways in control of energy
homeostasis is only partly understood. Here we show that selective Pten ablation in leptin-
sensitive neurons (Pten ΔObRb) results in enhanced Pi3k activation in these cells and
reduces adiposity by increasing energy expenditure. White adipose tissue (WAT) of Pten
ΔObRb mice shows characteristics of brown adipose tissue (BAT), reflected by increased
mitochondrial content and Ucp1 expression resulting from enhanced leptin-stimulated …
Summary
The contribution of different leptin-induced signaling pathways in control of energy homeostasis is only partly understood. Here we show that selective Pten ablation in leptin-sensitive neurons (PtenΔObRb) results in enhanced Pi3k activation in these cells and reduces adiposity by increasing energy expenditure. White adipose tissue (WAT) of PtenΔObRb mice shows characteristics of brown adipose tissue (BAT), reflected by increased mitochondrial content and Ucp1 expression resulting from enhanced leptin-stimulated sympathetic nerve activity (SNA) in WAT. In contrast, leptin-deficient ob/ob-PtenΔObRb mice exhibit unaltered body weight and WAT morphology compared to ob/ob mice, pointing to a pivotal role of endogenous leptin in control of WAT transdifferentiation. Leanness of PtenΔObRb mice is accompanied by enhanced sensitivity to insulin in skeletal muscle. These data provide direct genetic evidence that leptin-stimulated Pi3k signaling in the CNS regulates energy expenditure via activation of SNA to perigonadal WAT leading to BAT-like differentiation of WAT.
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