Date of Award

2021

Document Type

Thesis

Degree Name

Master of Science (MS)

Department

Biological Sciences

Committee Chair

Ahmed Lawan

Committee Member

Jerome Baudry

Committee Member

Bruce Stallsmith

Subject(s)

Phosphatases, Glucose--Metabolism, Lipids--Metabolism, Metabolism--Disorders--Animal models

Abstract

The function of MKP-2 in metabolism and metabolic diseases remains largely unknown. In obese conditions mitogen-activated protein kinase (MAPK) pathway get dysfunctional and MAP kinase phosphatases (MKPs) play major roles in regulating the activities of MAPKs. We examined the regulation of MKP-2 expression in vivo, under physiological and pathological conditions, in the liver and other insulin responsive tissues using diet-induced obesity models using novel MKP-2 knockout mice. Also, we examined MKP-2 expression in vitro using insulin sensitive cell lines. We found that MKP-2 is expressed in insulin-sensitive tissues/cells and overexpression may delay muscle cell differentiation. Our novel data demonstrate that under high fat-diet feeding conditions MKP-2 knockout mice are insulin sensitive and resistant to diet-induced obesity compared to MKP-2 wild type mice. We demonstrate that, in obese conditions, MKP-2 is overexpressed in the liver resulting in inactivation of MAPKs and thereby promoting development of obesity, fatty liver and metabolic dysfunction.

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