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Publication
Loss of Ron receptor signaling leads to reduced obesity, diabetic phenotypes and
hepatic steatosis in response to high-fat diet in mice.
Authors Stuart WD, Brown NE, Paluch AM, Waltz SE
Submitted By Susan Waltz on 7/24/2015
Status Published
Journal American journal of physiology. Endocrinology and metabolism
Year 2015
Date Published 4/1/2015
Volume : Pages 308 : E562 - E572
PubMed Reference 25648832
Abstract The Ron receptor tyrosine kinase is a heterodimeric, membrane-spanning
glycoprotein that participates in divergent processes, including proliferation,
motility, and modulation of inflammatory responses. We observed male C57BL/6
mice with a global deletion of the Ron tyrosine kinase signaling domain
(TK(-/-)) to be leaner compared with control (TK(+/+)) mice under a standard
diet. When fed a high-fat diet (HFD), TK(-/-) mice gained 50% less weight and
were more insulin sensitive and glucose tolerant than controls. Livers from HFD
TK(-/-) mice were considerably less steatotic and weighed significantly less
than TK(+/+) livers. Serum cytokine levels of HFD TK(-/-) mice were also
significantly altered compared with TK(+/+) mice. Fewer and smaller adipocytes
were present in the TK(-/-) mice on both control and HFD and were accompanied by
diminished adiponectin and peroxisome proliferator-activated receptor-?
expression. In vitro adipogenesis experiments suggested reduced differentiation
in TK(-/-) embryonic fibroblasts (MEFs) that was rescued by Ron reconstitution.
Likewise, signal transducer and activator of transcription (STAT)-3
phosphorylation was diminished in TK(-/-) MEFs but was increased after Ron
reconstitution. The adipogenic inhibitors, preadipocyte factor 1 and Sox9, were
elevated in TK(-/-) MEFs and increased in both groups after STAT3 silencing. In
total, these studies document a previously unknown function for the Ron receptor
in mediating HFD-induced obesity and metabolic dysregulation.




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