|KIM, HYUNSOOK - University Of California|
|YOUNG, SCOTT - Dow Chemical Company|
|Yokoyama, Wallace - Wally|
Submitted to: Journal of Agricultural and Food Chemistry
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 7/7/2013
Publication Date: 7/7/2013
Citation: Kim, H., Bartley, G.E., Young, S., Yokoyama, W.H. 2013. HPMC supplementation reduces fatty liver, intestinal permeability, and insulin resistance with altered hepatic gene expression in diet-induced obese mice. Journal of Agricultural and Food Chemistry. 61(26):6404-6411.
Interpretive Summary: Viscous soluble dietary fibers are known to reduce plasma cholesterol. We have also shown that it prevents many of the characteristics of metabolic syndrome when supplemented in high fat diets fed to hamsters or mice. In this study a global analysis of all genes in the liver were analyzed from mice fed high fat diets with or without hydroxipropyl methylcellulose (HPMC). For the first time we found that glucocorticoid binding globulin gene expression was reduced. Glucocorticoids are known to regulate energy metabolism and induce diabetes and this finding suggests another role for viscous dietary fibers.
Technical Abstract: The effects of hydroxypropyl methylcellulose (HPMC), a highly viscous nonfermentable soluble dietary fiber, were evaluated on global hepatic gene profiles, steatosis and insulin resistance in high-fat (HF) diet-induced obese (DIO) mice. DIO C57BL/6J mice were fed a HF diet supplemented with either 6% HPMC or 6% microcrystalline cellulose (MCC). The effect of HPMC on hepatic gene expression was analyzed by exon microarray and real-time PCR. Glucose and insulin tolerance and intestinal permeability were also assessed. HPMC-fed mice exhibited significantly reduced body weight gain, liver weight, and reduced areas under the curve for 2-h insulin and glucose responses. HPMC significantly decreased HF diet-induced intestinal permeability and enhanced insulin sensitivity and glucose metabolism. HPMC upregulated hepatic genes related to fatty acid oxidation, cholesterol and bile acid synthesis, cellular activation of glucocorticoid (bile acid recycling), and downregulated genes related to oxidative stress, triglyceride synthesis, and polyunsaturated fatty acid elongation. Pathway analysis of microarray data identified lipid metabolism and cardiovascular diseases as being differentially regulated by HPMC. HPMC consumption ameliorates the effects of a HF diet on insulin resistance, hepatic lipid accumulation, glucocorticoid-related bile acid recycling, oxidative stress, weight gain, as well as intestinal permeability.