|SEO, KUN-HO - Konkuk University|
|KIM, HONG-SEOK - Konkuk University|
|KIM, DONG-HYEON - Konkuk University|
|CHON, JUNG-WHAN - Konkuk University|
|KIM, HYUNSOOK - Konkuk University|
|Yokoyama, Wallace - Wally|
Submitted to: PLoS ONE
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 11/18/2016
Publication Date: 12/15/2016
Citation: Seo, K., Bartley, G.E., Tam, C.C., Kim, H., Kim, D., Chon, J., Kim, H., Yokoyama, W.H. 2016. Chardonnay grape seed flour ameliorates hepatic steatosis and insulin resistance via altered hepatic gene expression for oxidative stress, inflammation, and lipid and ceramide synthesis in diet-induced obese mice. PLoS One. 11(12):E0167680. doi:10.1371/journal.pone.0167680.
Interpretive Summary: Mice were fed a high fat diet until they became obese and insulin resistant. The diet induced obese mice were continued on the high fat diet or high fat diet supplemented with Chardonnay grape seed flour. The grape seed flour reduced plasma cholesterol, body weight, abdominal fat weight, and other characteristics of obesity related metabolic dysfunction. Analysis of genes expressed in the liver by microarray showed that expression of genes for inflammation and oxidative stress were reduced while genes for fat oxidation and bile acids were increased. This study extends our previous research that showed that grape seed flour prevents metabolic dysfunction in normal weight mice placed on high fat diets, and shows that metabolic functions and weight are normalized in already obese mice.
Technical Abstract: Diet-induced obese (DIO) mice were fed high-fat (HF) diets containing either partially defatted flavonoid-rich Chardonnay grape seed flour (ChrSd) or microcrystalline cellulose (MCC, control) for 5 weeks in order to determine whether ChrSd improved insulin resistance and the pathogenesis of hepatic steatosis. The 2-h insulin and glucose areas under the curves were significantly lowered by ChrSd, indicating that ChrSd improved insulin sensitivity and glucose metabolism. ChrSd intake also significantly reduced body weight gain, liver and adipose tissue weights, hepatic lipid content, and plasma low-density lipoprotein (LDL)-cholesterol, despite a significant increase in food intake. Exon microarray analysis of hepatic gene expression revealed down-regulation of genes related to triglyceride and ceramide synthesis, immune response, oxidative stress, and inflammation, and up-regulation of genes related to fatty acid oxidation, cholesterol, and bile acid synthesis. Expression of leptin receptor was up-regulated, suggesting enhanced hepatic leptin sensitivity. Pathway analysis of the microarray data revealed that lipid and cholesterol metabolism, and infectious and metabolic disease pathways were differentially regulated by ChrSd. In conclusion, ChrSd ameliorated the effects of a HF diet on weight gain, insulin resistance, and progression of hepatic steatosis in DIO mice via modulation of hepatic expression of genes related to oxidative stress, inflammation, and lipid and cholesterol metabolism.