PMID- 33574566 OWN - NLM STAT- MEDLINE DCOM- 20220125 LR - 20221030 IS - 1476-5497 (Electronic) IS - 0307-0565 (Print) IS - 0307-0565 (Linking) VI - 45 IP - 6 DP - 2021 Jun TI - Integrative analysis of physiological responses to high fat feeding with diffusion tensor images and neurochemical profiles of the mouse brain. PG - 1203-1214 LID - 10.1038/s41366-021-00775-9 [doi] AB - BACKGROUND: Obesity proceeds with important physiological and microstructural alterations in the brain, but the precise relationships between the diet and feeding status, its physiological responses, and the observed neuroimaging repercussions, remain elusive. Here, we implemented a mouse model of high fat diet (HFD) feeding to explore specific associations between diet, feeding status, phenotypic and endocrine repercussions, and the resulting microstructural and metabolic alterations in the brain, as detected by diffusion tensor imaging (DTI) and neurochemical metabolic profiling. METHODS: Brain DTI images were acquired from adult male C57BL6/J mice after 6 weeks of HFD, or standard diet (SD) administrations, both under the fed, and overnight fasted conditions. Metabolomic profiles of the cortex (Ctx), hippocampus (Hipc), and hypothalamus (Hyp) were determined by (1)H high-resolution magic angle spinning (HRMAS) spectroscopy, in cerebral biopsies dissected after microwave fixation. Mean diffusivity (MD), fractional anisotropy (FA) maps, and HRMAS profiles were complemented with determinations of phenotypic alterations and plasma levels of appetite-related hormones, measured by indirect calorimetry and multiplex assays, respectively. We used Z-score and alternating least squares scaling (ALSCAL) analysis to investigate specific associations between diet and feeding status, physiological, and imaging parameters. RESULTS: HFD induced significant increases in body weight and the plasma levels of glucose and fatty acids in the fed and fasted conditions, as well as higher cerebral MD (Ctx, Hipc, Hyp), FA (Hipc), and mobile saturated fatty acids resonances (Ctx, Hipc, Hyp). Z-score and ASLCAL analysis identified the precise associations between physiological and imaging variables. CONCLUSIONS: The present study reveals that diet and feeding conditions elicit prominent effects on specific imaging and spectroscopic parameters of the mouse brain that can be associated to the alterations in phenotypic and endocrine variables. Together, present results disclose a neuro-inflammatory response to HFD, characterized primarily by vasogenic edema and compensatory responses in osmolyte concentrations. FAU - Guadilla, Irene AU - Guadilla I AUID- ORCID: 0000-0002-3932-0840 AD - Instituto de Investigaciones Biomedicas "Alberto Sols" CSIC-UAM, Madrid, Spain. FAU - Lizarbe, Blanca AU - Lizarbe B AD - Instituto de Investigaciones Biomedicas "Alberto Sols" CSIC-UAM, Madrid, Spain. FAU - Barrios, Laura AU - Barrios L AD - Centro Tecnico de Informatica CSIC, Madrid, Spain. FAU - Cerdan, Sebastian AU - Cerdan S AUID- ORCID: 0000-0001-9965-0270 AD - Instituto de Investigaciones Biomedicas "Alberto Sols" CSIC-UAM, Madrid, Spain. FAU - Lopez-Larrubia, Pilar AU - Lopez-Larrubia P AUID- ORCID: 0000-0002-5141-8736 AD - Instituto de Investigaciones Biomedicas "Alberto Sols" CSIC-UAM, Madrid, Spain. plopez@iib.uam.es. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20210211 PL - England TA - Int J Obes (Lond) JT - International journal of obesity (2005) JID - 101256108 SB - IM MH - Animals MH - Body Weight/physiology MH - *Brain/diagnostic imaging/physiology MH - Brain Chemistry/*physiology MH - *Diet, High-Fat MH - *Diffusion Tensor Imaging MH - Male MH - Mice MH - Mice, Inbred C57BL PMC - PMC8159736 COIS- The authors declare that they have no conflict of interest. EDAT- 2021/02/13 06:00 MHDA- 2022/01/27 06:00 PMCR- 2021/02/11 CRDT- 2021/02/12 06:02 PHST- 2020/10/08 00:00 [received] PHST- 2021/01/21 00:00 [accepted] PHST- 2020/12/28 00:00 [revised] PHST- 2021/02/13 06:00 [pubmed] PHST- 2022/01/27 06:00 [medline] PHST- 2021/02/12 06:02 [entrez] PHST- 2021/02/11 00:00 [pmc-release] AID - 10.1038/s41366-021-00775-9 [pii] AID - 775 [pii] AID - 10.1038/s41366-021-00775-9 [doi] PST - ppublish SO - Int J Obes (Lond). 2021 Jun;45(6):1203-1214. doi: 10.1038/s41366-021-00775-9. Epub 2021 Feb 11.