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Transcriptomic Analysis of High Fat Diet Fed Mouse Brain Cortex.

ABSTRACT: High fat diet can lead to metabolic diseases such as obesity and diabetes known to be chronic inflammatory diseases with high prevalence worldwide. Recent studies have reported cognitive dysfunction in obese patients is caused by a high fat diet. Accordingly, such dysfunction is called "type 3 diabetes" or "diabetic dementia." Although dysregulation of protein-coding genes has been extensively studied, profiling of non-coding RNAs including long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs) has not been reported yet. Therefore, the objective of this study was to obtain profiles of diverse RNAs and determine their patterns of alteration in high fat fed brain cortex compared to normal brain cortex. To investigate regulatory roles of both coding and non-coding RNAs in high fat diet brain, we performed RNA sequencing of ribosomal RNA-depleted RNAs and identified genome-wide lncRNAs and circRNAs expression and co-expression patterns of mRNAs in high fat diet mouse brain cortex. Our results showed expression levels of mRNAs related to neurogenesis, synapse, and calcium signaling were highly changed in high fat diet fed cortex. In addition, numerous differentially expressed lncRNAs and circRNAs were identified. Our study provides valuable expression profiles and potential function of both coding and non-coding RNAs in high fat diet fed brain cortex.

SUBMITTER: Yoon G

PROVIDER: S-EPMC6389608 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Transcriptomic Analysis of High Fat Diet Fed Mouse Brain Cortex.

Yoon Gwangho G Cho Kyung A KA Song Juhyun J Kim Young-Kook YK

Frontiers in genetics 20190219

High fat diet can lead to metabolic diseases such as obesity and diabetes known to be chronic inflammatory diseases with high prevalence worldwide. Recent studies have reported cognitive dysfunction in obese patients is caused by a high fat diet. Accordingly, such dysfunction is called "type 3 diabetes" or "diabetic dementia." Although dysregulation of protein-coding genes has been extensively studied, profiling of non-coding RNAs including long non-coding RNAs (lncRNAs) and circular RNAs (circR ...[more]

PMID: 30838024

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Project description:BackgroundDietary fat intake affects brain composition and function. Different types of dietary fatty acids alter species and abundance of brain lipids in mice. The aim of this study is to explore whether the changes are effective through gut microbiota.MethodsIn our study, 8-week-old male C57BL/6 mice were randomly divided into 7 groups and fed with high-fat diet (HFD) with different fatty acid compositions, control (CON) group, long-chain saturated fatty acid (LCSFA) group, medium-chain saturated fatty acid (MCSFA) group, n-3 polyunsaturated fatty acid (n-3 PUFA) group, n-6 polyunsaturated fatty acid (n-6 PUFA) group, monounsaturated fatty acid (MUFA) group and trans fatty acid (TFA) group. Then, the fecal microbiota transplant (FMT) was performed in other pseudo germ-free mice after antibiotic treatment. The experimental groups were orally perfused with gut microbiota that induced by HFD with different types of dietary fatty acids. The mice were fed with regular fodder before and after FMT. High-performance liquid chromatography-mass spectrometry (LC-MS) was used to analysis the composition of fatty acids in the brain of HFD-fed mice and hippocampus of mice treated with FMT which was collected from HFD-fed mice.ResultsThe content of acyl-carnitines (AcCa) increased and lysophosphatidylgylcerol (LPG) decreased in all kinds of HFD groups. phosphatidic acids (PA), phosphatidylethanolamine (PE) and sphingomyelin (SM) contents were significantly increased in the n-6 PUFA-fed HFD group. The HFD elevated the saturation of brain fatty acyl (FA). Lysophosphatidylcholine (LPC), lysodi-methylphosphatidylethanolamine (LdMePE), monolysocardiolipin (MLCL), dihexosylceramides (Hex2Cer), and wax ester (WE) significantly increased after LCSFA-fed FMT. MLCL reduced and cardiolipin (CL) raised significantly after n-3 PUFA-fed FMT.ConclusionsThe study revealed, HFD and FMT in mice had certain effects on the content and composition of fatty acids in the brain, especially on glycerol phospholipid (GP). The change of AcCa content in FA was a good indicator of dietary fatty acid intake. By altering the fecal microbiota, dietary fatty acids might affect brain lipids.

Project description:Higher dietary intakes of saturated fatty acid increase the risk of developing Alzheimer's disease and dementia, and even in people without diabetes higher glucose levels may be a risk factor for dementia. The mechanisms causing neuronal dysfunction and dementia by consuming high-fat diet degrading the integrity of the blood-brain barrier (BBB) has been suggested but are not yet fully understood, and metabolic state of the brain by this type of insult is still veiled. The objective of this study was to investigate the effect of high-fat diet on the brain metabolism by a multimodal imaging method using the hyperpolarizedcarbon 13 (13C)-pyruvate magnetic resonance (MR) spectroscopy and dynamic contrast-enhanced MR imaging in conjunction with the biochemical assay and the behavior test in a mouse model fed high-fat diet (HFD). In mice were fed 60% HFD for 6?months, hyperpolarized [1-13C] pyruvate MR spectroscopy showed decreased perfusion (p?<?0.01) and increased conversion from pyruvate to lactate (p?<?0.001) in the brain. The hippocampus and striatum showed the highest conversion ratio. The functional integrity of the blood-brain barrier tested by dynamic contrast-enhanced MR imaging showed no difference to the control. Lactate was increased in the cortex (p?<?0.01) and striatum (p?<?0.05), while PDH activity was decreased in the cortex (p?<?0.01) and striatum (p?<?0.001) and the phosphorylated PDH was increased in the striatum (p?<?0.05). Mice fed HFD showed less efficiency in learning memory compared with control (p?<?0.05). To determine whether hyperpolarized 13C-pyruvate magnetic resonance (MR) spectroscopy could detect a much earier event in the brain. Mice fed HFD for 3?months did not show a detectable cognitive decline in water maze based learning memory. Hyperpolarized [1-13C] pyruvate MR spectroscopy showed increased lactate conversion (P?<?.001), but no difference in cerebral perfusion. These results suggest that the increased hyperpolarized [1-13C] lactate signal in the brain of HFD-fed mice represent that altered metabolic alteration toward to glycolysis and hypoperfusion by the long-term metabolic stress by HFD further promote to glycolysis. The hyperpolarized [1-13C] pyruvate MR spectroscopy can be used to monitor the brain metabolism and will provide information helpful to understand the disease process.

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Transcriptomic Analysis of High Fat Diet Fed Mouse Brain Cortex.

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Transcriptomic Analysis of High Fat Diet Fed Mouse Brain Cortex.

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