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Blocking Fas signaling prevents obesity associated inflammation, insulin resistance, and hepatosteatosis

Title
Blocking Fas signaling prevents obesity associated inflammation, insulin resistance, and hepatosteatosis
Author
배수민
Advisor(s)
이상경
Issue Date
2018-02
Publisher
한양대학교
Degree
Master
Abstract
Apoptosis in adipose tissue and liver is a main event in the development of obesity related inflammation, insulin resistance, and hepatosteatosis. Both adipocytes and the infiltrating immune cells in adipose tissue are the key contributors to the formation of systemic inflammatory condition. In addition, apoptosis in the liver under high caloric diet condition also plays an important role in disrupting metabolic homeostasis. Fas receptor (CD95) which is over-expressed when both human and rodents are in obese condition is mainly involved in apoptotic pathways in the liver and adipose tissue. Apoptosis happens when Fas signaling is activated and ultimately causes alternative inflammatory pathway, secreting various cytokines which contribute to inflammation, eventually impairing the insulin signaling. We hypothesized that blocking Fas mediated apoptosis would reverse the inflammatory state of obese mice and improve the obesity-associated metabolic dysfunctions by modulating the systemic immune response. In this study, we have used small peptide called Fas blocking peptide (FBP). We have found that blocking Fas signaling in both liver and adipose tissue by FBP inhibits highly elevated supplementation of immune cells, macrophage polarization, apoptosis, production of inflammatory cytokines and insulin resistance. Consequently, treatment of FBP reversed the inflammation, insulin resistance and hepatic steatosis in high fat diet induced obese mouse model. Our results suggest that blocking Fas-mediated apoptotic pathways in adipose tissue and liver may be used as a therapeutic strategy in obesity associated inflammation, insulin resistance and hepatosteatosis.
URI
http://www.dcollection.net/handler/hanyang/000000105584http://repository.hanyang.ac.kr/handle/20.500.11754/68164
Appears in Collections:
GRADUATE SCHOOL[S](대학원) > BIOENGINEERING(생명공학과) > Theses (Master)
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