Elevated Hypothalamic TCPTP in Obesity Contributes to Cellular Leptin Resistance

Full text for this resource is not available from the Research Repository.

Loh, Kim, Fukushima, Atsushi, Zhang, Xinmei, Galic, Sandra, Briggs, Dana, Enriori, Pablo J, Simonds, Stephanie, Wiede, Florian, Reichenbach, Alexander, Hauser, Christine, Sims, Natalie A, Bence, Kendra K, Zhang, Sheng, Zhang, Zhong-Yi, Kahn, Barbara B, Neel, Benjamin G, Andrews, Zane B, Cowley, Michael A and Tiganis, Tony (2011) Elevated Hypothalamic TCPTP in Obesity Contributes to Cellular Leptin Resistance. Cell Metabolism, 14 (5). pp. 684-699. ISSN 1550-4131

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.

Dimensions Badge

Altmetric Badge

Item type Article
URI https://vuir.vu.edu.au/id/eprint/9095
DOI https://doi.org/10.1016/j.cmet.2011.09.011
Official URL http://www.sciencedirect.com/science/article/pii/S...
Subjects Historical > Faculty/School/Research Centre/Department > Institute of Sport, Exercise and Active Living (ISEAL)
Historical > FOR Classification > 1101 Medical Biochemistry and Metabolomics
Historical > SEO Classification > 970111 Expanding Knowledge in the Medical and Health Sciences
Keywords ResPubID23494, leptin resistance, protein tyrosine phosphatase 1B, PTP1B, hypothalamic levels, neuronal cells
Citations in Scopus 135 - View on Scopus
Download/View statistics View download statistics for this item

Search Google Scholar

Repository staff login