| Literature DB >> 22000926 |
Kim Loh1, Atsushi Fukushima, Xinmei Zhang, Sandra Galic, Dana Briggs, Pablo J Enriori, Stephanie Simonds, Florian Wiede, Alexander Reichenbach, Christine Hauser, Natalie A Sims, Kendra K Bence, Sheng Zhang, Zhong-Yin Zhang, Barbara B Kahn, Benjamin G Neel, Zane B Andrews, Michael A Cowley, Tony Tiganis.
Abstract
In obesity, anorectic responses to leptin are diminished, giving rise to the concept of "leptin resistance." Increased expression of protein tyrosine phosphatase 1B (PTP1B) has been associated with the attenuation of leptin signaling and development of cellular leptin resistance. Here we report that hypothalamic levels of the tyrosine phosphatase TCPTP are also elevated in obesity to attenuate the leptin response. We show that mice that lack TCPTP in neuronal cells have enhanced leptin sensitivity and are resistant to high-fat-diet-induced weight gain and the development of leptin resistance. Also, intracerebroventricular administration of a TCPTP inhibitor enhances leptin signaling and responses in mice. Moreover, the combined deletion of TCPTP and PTP1B in neuronal cells has additive effects in the prevention of diet-induced obesity. Our results identify TCPTP as a critical negative regulator of hypothalamic leptin signaling and causally link elevated TCPTP to the development of cellular leptin resistance in obesity.Entities:
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Year: 2011 PMID： 22000926 PMCID： PMC3263335 DOI： 10.1016/j.cmet.2011.09.011
Source DB: PubMed Journal: Cell Metab ISSN： 1550-4131 Impact factor: 27.287