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β-aminoisobutyric acid attenuates LPS-induced inflammation and insulin resistance in adipocytes through AMPK-mediated pathway

Cited 22 time in Web of Science Cited 19 time in Scopus
Authors
Jung, Tae Woo; Park, Hyung Sub; Choi, Geum Hee; Kim, Daehwan; Lee, Taeseung
Issue Date
2018-03-28
Publisher
BioMed Central
Citation
Journal of Biomedical Science, 25(1):27
Keywords
BAIBAAMPKNFκBInflammationInsulin resistanceAdipocyte
Abstract
Background
β-aminoisobutyric acid (BAIBA) is produced in skeletal muscle during exercise and has beneficial effects on obesity-related metabolic disorders such as diabetes and non-alcoholic fatty liver disease. Thus, it is supposed to prevent high fat diet (HFD)-induced inflammation and insulin resistance in adipose tissue though anti-inflammatory effects in obesity. Previous reports have also demonstrated strong anti-inflammatory effects of BAIBA.

Methods
We used BAIBA treated fully differentiated 3T3T-L1 mouse adipocytes to investigate the effects of exogenous BAIBA on inflammation and insulin signaling in adipocytes. Insulin signaling-mediated proteins and inflammation markers were measured by Western blot analysis. Secretion of pro-inflammatory cytokines were measured by ELISA. Lipid accumulation in differentiated 3 T3-L1 cells was stained by Oil red-O. Statistical analysis was performed by ANOVA and students t test.

Results
BAIBA treatment suppressed adipogenesis assessed by adipogenic markers as well as lipid accumulation after full differentiation. We showed that BAIBA treatment stimulated AMP-activated protein kinase (AMPK) phosphorylation in a dose-dependent manner and lipopolysaccharide (LPS)-induced secretion of pro-inflammatory cytokines such as TNFα and MCP-1 was abrogated in BAIBA-treated 3 T3-L1 cells. Treatment of 3 T3-L1 cells with BAIBA reduced LPS-induced NFκB and IκB phosphorylation. Furthermore, BAIBA treatment ameliorated LPS-induced impairment of insulin signaling measured by IRS-1 and Akt phosphorylation and fatty acid oxidation. Suppression of AMPK by small interfering (si) RNA significantly restored these changes.

Conclusions
We demonstrated anti-inflammatory and anti-insulin resistance effects of BAIBA in differentiated 3 T3-L1 cells treated with LPS through AMPK-dependent signaling. These results provide evidence for the beneficial effects of BAIBA not only in liver and skeletal muscle cells but also in adipose tissue.
ISSN
1423-0127
Language
English
URI
https://hdl.handle.net/10371/139762
DOI
https://doi.org/10.1186/s12929-018-0431-7
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College of Medicine/School of Medicine (의과대학/대학원)Surgery (외과학전공)Journal Papers (저널논문_외과학전공)
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