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Nutrients. 2018 Oct 3;10(10). pii: E1415. doi: 10.3390/nu10101415.

Luteolin Targets the Toll-Like Receptor Signaling Pathway in Prevention of Hepatic and Adipocyte Fibrosis and Insulin Resistance in Diet-Induced Obese Mice.

Author information

1
Department of Food Science and Nutrition, Kyungpook National University, 1370 San-Kyuk Dong Puk-Ku, Daegu 41566, Korea. savage20@naver.com.
2
Center for Food and Nutritional Genomics Research, Kyungpook National University, 1370 San-Kyuk Dong Puk-Ku, Daegu 41566, Korea. savage20@naver.com.
3
Department of Food Science and Nutrition, Kyungpook National University, 1370 San-Kyuk Dong Puk-Ku, Daegu 41566, Korea. mschoi@knu.ac.kr.
4
Center for Food and Nutritional Genomics Research, Kyungpook National University, 1370 San-Kyuk Dong Puk-Ku, Daegu 41566, Korea. mschoi@knu.ac.kr.

Abstract

This study was to investigate the protective role of luteolin on inflammation-mediated metabolic diseases, focusing on the role of luteolin in the modulation of the Toll-like receptor (TLR) signaling pathway. C57BL/6J mice were fed a normal, high-fat, or high-fat + 0.005% (w/w) luteolin diet for 16 weeks. Luteolin improved chronic low-grade inflammation by modulating the TLR signaling pathway, resulting in reduced pro-inflammatory cytokines and macrophage accumulation. A positive relationship was detected between gene expressions of Tlr5, Map2k7, Mapk12, Mapk13, and Mapk9 and lipogenesis in epididymal white adipose tissue (eWAT) of luteolin-treated mice, which was linked to attenuation of hepatic lipotoxicity by increasing free fatty acid (FFA) flux to the WAT. Luteolin prevented fibrosis by decreasing extracellular matrix accumulation and cathepsin gene expressions, while enhancing the hepatic antioxidant system. Emr1 and Ccl7, important markers inducing low-grade inflammation, were affected by advanced age and greater body weight, which were normalized by luteolin treatment. Luteolin improved insulin resistance by normalizing pancreatic islet dysfunction and differentially modulating the plasma glucagon-like peptide-1 and gastric inhibitory polypeptide levels. Our results suggest that luteolin ameliorates diet-induced obesity and its comorbidities. Overall, this study provides novel insights into the effect of luteolin on the links among adiposopathy, insulin resistance, hepatic steatosis, and fibrosis.

KEYWORDS:

Toll-like signaling pathway; fibrosis; inflammation; luteolin; obesity

PMID:
30282902
PMCID:
PMC6213163
DOI:
10.3390/nu10101415
[Indexed for MEDLINE]
Free PMC Article

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