Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
11026218 | Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease | 2018 | 9 Pages |
Abstract
Dietary fructose is a major contributor to the epidemic of diabetes and obesity, and it is an excellent model to study metabolic syndrome. Based on previous studies that Bgn gene occupies a central position in a network of genes in the brain in response to fructose consumption, we assessed the capacity of Bgn to modulate the action of fructose on brain and body. We exposed male biglycan knockout mice (Bgn0/â) to fructose for 7â¯weeks, and results showed that Bgn0/â mice compensated for a decrement in learning and memory performance when exposed to fructose. These results were consistent with an attenuation of the action of fructose on hippocampal CREB levels. Fructose also reduced the levels of CREB and BDNF in primary hippocampal neuronal cultures. Bgn siRNA treatment abolished these effects of fructose on CREB and BDNF levels, in conjunction with a reduction in a fructose-related increase in Bgn protein. In addition, fructose consumption perturbed the systemic metabolism of glucose and lipids, that were also altered in the Bgn0/ mice. Transcriptomic profiling of hypothalamus, hippocampus, and liver supported the regulatory action of Bgn on key molecular pathways involved in metabolism, immune response, and neuronal plasticity. Overall results underscore the tissue-specific role of the extracellular matrix in the regulation of metabolism and brain function, and support Bgn as a key modulator for the impact of fructose across body and brain.
Keywords
ECMCREBORONTCHDLTrkBtropomyosin related kinase BTCAAUCBDNFhigh-density lipoproteinIPGTTintraperitoneal glucose tolerance testTranscriptomeOil red OCognitionBrain-derived neurotrophic factorExtracellular matrixMetabolismarea under the curvewild typeHypothalamusHippocampuscAMP response element binding proteintricarboxylic acid cycleLiver
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Authors
Zhe Ying, Hyae Ran Byun, Qingying Meng, Emily Noble, Guanglin Zhang, Xia Yang, Fernando Gomez-Pinilla,