Mass spectrometry imaging of mice brain lipid profile changes over time under high fat diet

Abstract

Overweight and obesity have been shown to significantly affect brain structures and size. Obesity has been associated with cerebral atrophy, alteration of brain functions, including cognitive impairement, and psychiatric diseases such as depression. Given the importance of lipids in the structure of the brain, here, by using 47 mice fed a high fat diet (HFD) with 60% calories from fat (40% saturated fatty acids) and 20% calories from carbohydrates and age-matched control animals on a normal chow diet, we examined the effects of HFD and diet-induced obesity on the brain lipidome. Using a targeted liquid chromatography mass spectrometry analysis and a non-targeted mass spectrometry MALDI imaging approach, we show that the relative concentration of most lipids, in particular brain phospholipids, is modified by diet-induced obesity (+ 40%of body weight). Use of a non-targeted MALDI-MS imaging approach further allowed define cerebral regions of interest (ROI) involved in eating behavior and changes in their lipid profile. Principal component analysis (PCA) of the obese/chow lipidome revealed persistence of some of the changes in the brain lipidome of obese animals even after their switch to chow feeding and associated weight loss. Altogether, these data reveal that HFD feeding rapidly modifies the murine brain lipidome. Some of these HFD-induced changes persist even after weight loss, implying that some brain sequelae caused by diet-induced obesity are irreversible.

Adipose transplantation improves olfactory function and neurogenesis via PKCα-involved lipid metabolism in Seipin Knockout mice

“…MALDI-MSI analysis of the SVZ lipid composition in the human brain revealed that the SVZ was rich in sphingomyelin and phosphatidylserine (PS) but de cient in PE or PC [16]. The levels of glycerophospholipid in the brain with metabolic diseases such as obesity and diabetes also changed signi cantly, and the changes in the content of PC and DG were directly proportional to the severity of the disease [18,34]. In the present study, we found that glycerophospholipids such as DG, PA, PE, and PC in the SVZ of KO mice were signi cantly increased.…”

Lipid Microcapsules Promoted Neural Stem Cell Survival in the Infarcted Area of Mice with Ischemic Stroke by Inducing Autophagy

“…The natural cell membrane has a phospholipid-based bilayer structure. Based on the theory of using the same material as the natural cell membrane, artificial cells or vesicles with lipid surfaces have been investigated over the past few decades. , To date, lipid vesicles have been developed as useful models of some properties of natural cells, enabling the study of signal transduction, cascade reactions, molecular/protein interactions, and transport. − More importantly, lipids represent more than half of the brain dry weight and play a pivotal role in brain integrity …”

“…21−25 More importantly, lipids represent more than half of the brain dry weight and play a pivotal role in brain integrity. 26 Except for being the major component of the cell membrane and brain tissue, lipids are also involved in the process of autophagy. 27 Considering that autophagy may promote cell survival in inappropriate living conditions, 28 lipid encapsulation may promote cell survival by not only providing a "living microenvironment" but also altering autophagy.…”

Spatial Heterogeneity of Brain Lipids in SIV-infected Macaques Treated with Antiretroviral Therapy

“…26.508302 doi: bioRxiv preprint (18,21). This is a major limitation as it is well described that lipid distribution is not uniform across brain regions (23,24), which likely occurs due to the region-specific expression of lipid breakdown genes and regional differences in structural lipid composition (25,26). Similarly, region-dependent neuropathological hallmarks of HIV are well recognized to occur, where certain brain regions are preferentially vulnerable to HIV-induced damage and others remain spared (4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15).…”

“…However, previous in vivo and ex vivo studies focused exclusively on profiling total lipid abundance using brain homogenate, without consideration of the spatial differences inherent in the lipid profile (18,21). This is a major limitation as it is well described that lipid distribution is not uniform across brain regions (23,24), which likely occurs due to the region-specific expression of lipid breakdown genes and regional differences in structural lipid composition (25,26). Similarly, region-dependent neuropathological hallmarks of HIV are well recognized to occur, where certain brain regions are preferentially vulnerable to HIV-induced damage and others remain spared (4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15).…”