Journal Article

Assessment of Chitosan-Affected Metabolic Response by Peroxisome Proliferator-Activated Receptor Bioluminescent Imaging-Guided Transcriptomic Analysis

Ho, Tin-Yun, Hsiang, Chien-Yun, Kao, Chia-Hung

2012

Overview

Chitosan has been widely used in food industry as a weight-loss aid and a cholesterol-lowering agent. Previous studies have shown that chitosan affects metabolic responses and contributes to anti-diabetic, hypocholesteremic, and blood glucose-lowering effects; however, the in vivo targeting sites and mechanisms of chitosan remain to be clarified. In this study, we constructed transgenic mice, which carried the luciferase genes driven by peroxisome proliferator-activated receptor (PPAR), a key regulator of fatty acid and glucose metabolism. Bioluminescent imaging of PPAR transgenic mice was applied to report the organs that chitosan acted on, and gene expression profiles of chitosan-targeted organs were further analyzed to elucidate the mechanisms of chitosan. Bioluminescent imaging showed that constitutive PPAR activities were detected in brain and gastrointestinal tract. Administration of chitosan significantly activated the PPAR activities in brain and stomach. Microarray analysis of brain and stomach showed that several pathways involved in lipid and glucose metabolism were regulated by chitosan. Moreover, the expression levels of metabolism-associated genes like apolipoprotein B (apoB) and ghrelin genes were down-regulated by chitosan. In conclusion, these findings suggested the feasibility of PPAR bioluminescent imaging-guided transcriptomic analysis on the evaluation of chitosan-affected metabolic responses in vivo. Moreover, we newly identified that downregulated expression of apoB and ghrelin genes were novel mechanisms for chitosan-affected metabolic responses in vivo.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Alzheimer's disease / Animals / Anticholesteremic Agents - pharmacology / Apolipoprotein B / Apolipoproteins / Apolipoproteins B - biosynthesis / Atherosclerosis / Autoimmune diseases / Biology / Blood glucose / Body weight loss / Brain / Brain - metabolism / Cardiovascular disease / Chitosan / Chitosan - pharmacology / Cholesterol / Deoxyribonucleic acid / Diabetes / Diabetes mellitus / DNA / DNA microarrays / Down-Regulation - drug effects / Fatty acids / Feasibility studies / Food industry / Food processing industry / Gastrointestinal system / Gastrointestinal tract / Gastrointestinal Tract - metabolism / Gene expression / Gene Expression Profiling / Genes / Genetic engineering / Ghrelin / Ghrelin - biosynthesis / Glucose / Glucose - metabolism / Homeostasis / Imaging / Ionizing radiation / Kinases / Lipid metabolism / Lipid Metabolism - drug effects / Lipids / Lipoproteins / Luciferase / Luminescent Measurements / Male / Materials Science / Medicine / Metabolic response / Metabolism / Mice / Mice, Transgenic / Neuroimaging / Organs / Parkinson's disease / Peroxisome proliferator-activated receptors / Peroxisome Proliferator-Activated Receptors - analysis / Peroxisome Proliferator-Activated Receptors - metabolism / Rodents / Stomach / Transgenic animals / Transgenic mice