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Biglycan gene connects metabolic dysfunction with brain disorder
- Source :
- Biochimica et biophysica acta. Molecular basis of disease, vol 1864, iss 12
- Publication Year :
- 2018
- Publisher :
- Elsevier BV, 2018.
-
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/−) to fructose for 7 weeks, and results showed that Bgn0/− 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.
- Subjects :
- Male
0301 basic medicine
Medical Biochemistry and Metabolomics
Hippocampal formation
Hippocampus
Mice
chemistry.chemical_compound
Cognition
0302 clinical medicine
Biglycan
2.1 Biological and endogenous factors
Aetiology
Cyclic AMP Response Element-Binding Protein
Cells, Cultured
Mice, Knockout
Brain Diseases
Cultured
biology
Liver
Hypothalamus
Neurological
Knockout mouse
Body Composition
Molecular Medicine
Mental health
Metabolic Networks and Pathways
Biochemistry & Molecular Biology
medicine.medical_specialty
Cells
Knockout
1.1 Normal biological development and functioning
Clinical Sciences
Fructose
CREB
Article
03 medical and health sciences
Underpinning research
Internal medicine
Glucose Intolerance
Neuroplasticity
Genetics
medicine
Animals
Obesity
Maze Learning
Molecular Biology
Metabolic and endocrine
Nutrition
Gene Expression Profiling
Neurosciences
Metabolism
Lipid Metabolism
Glucose
030104 developmental biology
Endocrinology
chemistry
biology.protein
Biochemistry and Cell Biology
Transcriptome
030217 neurology & neurosurgery
Subjects
Details
- ISSN :
- 09254439
- Volume :
- 1864
- Database :
- OpenAIRE
- Journal :
- Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease
- Accession number :
- edsair.doi.dedup.....262de88338504fc7943d386681430eaa