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Title: HPMC supplementation reduces abdominal fat content, intestinal permeability, inflammation, and insulin resistance in diet-induced obese mice

item KIM, HYUNSOOK - University Of California
item Bartley, Glenn
item YOUNG, SCOTT - Dow Chemical Company
item DAVIS, PAUL - University Of California
item Yokoyama, Wallace - Wally

Submitted to: Molecular Nutrition and Food Research
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 5/18/2012
Publication Date: 7/11/2012
Citation: Kim, H., Bartley, G.E., Young, S.A., Davis, P.A., Yokoyama, W.H. 2012. HPMC supplementation reduces abdominal fat content, intestinal permeability, inflammation, and insulin resistance in diet-induced obese mice. Molecular Nutrition and Food Research. 00:1-3. DOI: 10.1002/mnfr.201200082.

Interpretive Summary: Mice fed a high fat diet rapidly become obese and develop high blood cholesterol and triglycerides. It has become evident that fat storage cells or adipose not only store fat, but are the source of circulating cell signaling proteins, adipokines, such as leptin and adiponectin that affect other tissues. By looking at all genes expressed by high fat feeding and high fat supplemented with a viscous soluble dietary fiber, hydroxypropyl methylcellulose (HPMC), we found that HPMC was able to decrease the expression of genes known to be related to inflammation and immune responses. The research suggests that inflammation is the basis for the hyperlipidemias. High fat diets cause increased intestinal permeability to inflammatory products of bacterial cell degradation. The research also showed that HPMC also decreased intestinal permeability.

Technical Abstract: The effects of hydroxypropyl methylcellulose (HPMC), a highly viscous non-fermentable soluble dietary fiber, were evaluated on adipose tissue inflammation and insulin resistance in diet induced obese (DIO) mice fed a high fat (HF) diet supplemented with either HPMC or insoluble fiber. DIO C57BL/6J mice were fed a HF diet supplemented with 6% HPMC or 6% microcrystalline cellulose (MCC). Gene expression analyses of epididymal adipose tissue by exon microarray and real-time PCR along with glucose and insulin tolerance and intestinal permeability were assessed. HPMC fed mice exhibited significantly reduced body weight gain and adipose tissue weight as well as reduced areas under the curve for 2-hr insulin and glucose responses. HPMC significantly decreased HF diet induced intestinal permeability. Overall, HPMC enhanced insulin sensitivity and glucose metabolism and down-regulated genes related to inflammation and immune response, adipogenesis, and oxidative stress markers. IPA analysis of microarray data identified lipid metabolism, inflammatory disease, and acute phase response pathways as being differentially regulated by HPMC. Conclusions: These results suggest HPMC consumption ameliorates HF diet effects on obesity-induced insulin resistance, adipose tissue inflammatory and immune responses, weight gain, as well as intestinal permeability.