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The role that myeloid protein tyrosine phosphatase 1B (PTP1B) plays in obesity and type 2 diabetes with focus on neuroinflammation

Metz, T (2016) The role that myeloid protein tyrosine phosphatase 1B (PTP1B) plays in obesity and type 2 diabetes with focus on neuroinflammation. Master's Thesis / Essay, Behavioural and Cognitive Neurosciences.

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Abstract

Obesity and diabetes are a major health concern in the Western world. Protein tyrosine phosphatase-1B (PTP1B) is an attractive drug target for obesity and type 2 diabetes (T2D); it is known to negatively regulate both the insulin receptor and the leptin receptor. Mice lacking PTP1B are protected from diet induced insulin resistance and obesity. However, due to the potential anti-inflammatory role of PTP1B, investigation into the role of PTP1B in the immune system is needed. Microglia have been shown to be both increased in number and in activation in several disease states, such as stroke, dementia, depression and obesity. LysM is expressed in microglia, which are inflammatory cells in the central nervous system. Therefore the role of PTP1B in hypothalamic inflammation and whole-body metabolism was assessed using myeloid cell PTP1B knockout mice (Lysm-PTP1B) on either regular chow diet or high fat diet. Our aim was to investigate the role of myeloid PTP1B in obesity. Our research shows that high-fat feeding leads to increased serum leptin and insulin levels and these levels are reduced again in Lysm-PTP1B mice. However, the lack of myeloid PTP1B does not reduce the increased body weight of mice on high-fat diet. The Lysm-PTP1B mice are protected against ER-stress, but the increase in ER-stress under high-fat diet conditions cannot be reduced. Messenger RNA of several inflammatory mediators could not be detected in the hypothalamus. Strikingly, microglial inflammation markers are increased in high fat diet mice, but only in the knock-out group. This research indicates that inhibiting myeloid PTP1B restores serum insulin and leptin levels and might act through lowering hypothalamic ER-stress.

Item Type: Thesis (Master's Thesis / Essay)
Degree programme: Behavioural and Cognitive Neurosciences
Thesis type: Master's Thesis / Essay
Language: English
Date Deposited: 15 Feb 2018 08:11
Last Modified: 15 Feb 2018 08:11
URI: http://fse.studenttheses.ub.rug.nl/id/eprint/13743

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