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Published on: February 17, 2023
Elevated hypothalamic TCPTP in obesity contributes to cellular leptin resistance
Kim Loh1, Atsushi Fukushima, Xinmei Zhang
1Department of Biochemistry and Molecular Biology, Monash University, Victoria 3800, Australia.
Cell Metabolism
|October 18, 2011
Summary
Leptin resistance in obesity is worsened by elevated TCPTP in the hypothalamus. Inhibiting TCPTP enhances leptin sensitivity and prevents diet-induced obesity in mice.
Area of Science:
- Neuroendocrinology
- Metabolic disease research
Background:
- Obesity is characterized by diminished anorectic responses to leptin, termed "leptin resistance."
- Elevated protein tyrosine phosphatase 1B (PTP1B) is linked to impaired leptin signaling and cellular leptin resistance.
Purpose of the Study:
- To investigate the role of tyrosine phosphatase TCPTP in hypothalamic leptin signaling and obesity-related leptin resistance.
- To determine if TCPTP inhibition can ameliorate leptin resistance and prevent diet-induced obesity.
Main Methods:
- Assessed hypothalamic TCPTP levels in obese models.
- Generated mice lacking TCPTP in neuronal cells.
- Administered TCPTP inhibitor intracerebroventricularly.
- Studied combined deletion of TCPTP and PTP1B in neuronal cells.
Main Results:
- Hypothalamic TCPTP levels are elevated in obesity, attenuating leptin response.
- Mice lacking neuronal TCPTP exhibit enhanced leptin sensitivity and resistance to diet-induced obesity.
- TCPTP inhibition boosts leptin signaling and responses in mice.
- Combined deletion of TCPTP and PTP1B shows additive effects in preventing obesity.
Conclusions:
- TCPTP is identified as a key negative regulator of hypothalamic leptin signaling.
- Elevated hypothalamic TCPTP causally contributes to cellular leptin resistance in obesity.
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