Brief exposure of neuronal cells to levels of SCFAs observed in human systemic circulation impair lipid metabolism resulting in apoptosis.

Communication between gut microbiota and the brain is an enigma. Alterations in the gut microbial community affects enteric metabolite levels, such as short chain fatty acids (SCFAs). SCFAs have been proposed as a possible mechanism through which the gut microbiome modulate brain health and function. This study analyzed for the first time the effects of SCFAs at levels reported in human systemic circulation on SH-SY5Y human neuronal cell energy metabolism, viability, survival, and the brain lipidome. Cell and rat brain lipidomics was done using high resolution mass spectrometry (HRMS). Neuronal cells viability, survival and energy metabolism were analyzed via flow cytometer, immunofluorescence, and SeahorseXF platform. Lipidomics analysis demonstrated that SCFAs significantly remodeled the brain lipidome in vivo and in vitro. The most notable remodulation was observed in the metabolism of phosphatidylethanolamine plasmalogens, and mitochondrial lipids carnitine and cardiolipin. Increased mitochondrial mass, fragmentation, and hyperfusion occurred concomitant with the altered mitochondrial lipid metabolism resulting in decreased neuronal cell respiration, adenosine triphosphate (ATP) production, and increased cell death. This suggests SCFAs at levels observed in human systemic circulation can adversely alter the brain lipidome and neuronal cell function potentially negatively impacting brain health outcomes.

First insights into the honey bee (Apis mellifera) brain lipidome and its neonicotinoid-induced alterations associated with reduced self-grooming behavior.

Introduction: Honey bees (Apis mellifera) play key roles in food production performing complex behaviors, like self-grooming to remove parasites. However, the lipids of their central nervous system have not been examined, even though they likely play a crucial role in the performance of cognitive process to perform intricate behaviors. Lipidomics has greatly advanced our understanding of neuropathologies in mammals and could provide the same for honey bees. Objectives: The objectives of this study were to characterize the brain lipidome of adult honey bees and to assess the effect of clothianidin (a neurotoxic insecticide) on the brain lipid composition, gene expression, and performance of self-grooming behavior under controlled conditions (cage experiments). Methods: After seven days of exposure to oral sublethal doses of clothianidin, the bees were assessed for self-grooming behavior; their brains were dissected to analyze the lipidome using an untargeted lipidomics approach and to perform a high throughput RNAseq analysis. Results: Compared to all other organisms, healthy bee brain lipidomes contain unusually high levels of alkyl-ether linked (plasmanyl) phospholipids (51.42%) and low levels of plasmalogens (plasmenyl phospholipids; 3.46%). This could make it more susceptible to the effects of toxins in the environment. A positive correlation between CL 18:3/18:1/14:0/22:6, TG 6:0/11:2/18:1, LPE 18:0e and intense self-grooming was found. Sublethal doses of a neonicotinoid altered PC 20:3e/15:0, PC 16:0/18:3, PA 18:0/24:1, and TG 18:1/18:1/18/1 levels, and affected gene expression linked to GPI-anchor biosynthesis pathway and energy metabolism that may be partially responsible for the altered lipid composition. Conclusion: This study showed that lipidomics can reveal honey bee neuropathologies associated with reduced grooming behavior due to sublethal neonicotinoid exposure. The ease of use, unusual brain lipidome as well as characterized behaviors that are affected by the environment make honey bees a promising model organism for studying the neurolipidome and associations with neurobehavioral disorders.

The effects of clearcut harvesting on moss chloroplast lipidome and adaptation to light stress during boreal forest regeneration.

Moss plays an important role in boreal forest ecosystems as an understory bryophyte species. Clearcut harvesting is a common boreal forest regeneration method that can expose understory vegetation to abiotic stressors impeding their recovery following post-harvest conditions. Very little is known concerning how moss remodel their chloroplast lipidome to enhance photosynthetic performance for successful acclimation to light and water stress during boreal forest regeneration following clearcut harvesting. The chloroplast lipidome and photosynthetic performance of Sphagnum sp. and three feathermoss species (Pleurozium schreberi, Hylocomium splendens, and Ptilium crista-castrensis) from a boreal black spruce (Picea mariana) forest were assessed using liquid chromatography-mass spectrometry (LC-MS), photospectrometry, and light response curves. We observed an overall increase in monogalactosyldiacylglycerol (MGDG) and sulfoquinovosyldiacylglycerol (SQDG) and decrease in digalactosyldiacylglycerol (DGDG) and phosphatidylglycerol (PG). In addition, unsaturation of the chloroplast lipidome occurred concomitant with photoprotection by carotenoid pigments to enhance the efficiency and photosynthetic capacity in moss exposed to light and water stress following clearcut harvesting. This appears to be a successful acclimation strategy used by moss to circumvent light stress during boreal forest regeneration following clearcut harvesting. These findings could be of significance in the development of boreal forest management strategies following resource harvesting.

Intraperitoneal Administration of Short-Chain Fatty Acids Improves Lipid Metabolism of Long-Evans Rats in a Sex-Specific Manner.

Short-chain fatty acids (SCFAs) are microbial metabolites, mainly generated by the action of gut microbiota on dietary fibers. Acetate, propionate, and butyrate are the three main SCFAs produced typically in a 60:20:20 molar ratio in the colon. Acetate, propionate, and butyrate, when given individually as supplements, have shown a protective role in obesity and hyperglycemia; however, the sex-specific effects of a mixture of SCFAs, when given in 60:20:20 ratio, on the regulation of lipid metabolism and lipid profile are not known. Male and female Long-Evans rats were given a mixture of SCFAs (acetate, propionate, and butyrate; molar ratio 60:20:20) each day for seven days intraperitoneally; plasma and hepatic lipids, gene expression, and lipidomics profile were analyzed. SCFAs significantly decreased plasma and hepatic triglycerides and cholesterol in males, whereas the fatty acyl composition of cholesteryl esters, triglycerides, and phospholipids was modulated in females. SCFAs decreased the mRNA expression of hepatic acetyl-CoA carboxylase-1 in both males and females. Our findings demonstrate for the first time that SCFAs (60:20:20) improved plasma and hepatic lipid levels and fatty acyl composition in a manner that may provide cardio-protective and anti-inflammatory effects in both sexes, via independent mechanisms.

Targeting Modified Lipids during Routine Lipidomics Analysis using HILIC and C30 Reverse Phase Liquid Chromatography coupled to Mass Spectrometry.

Lipids are important biomolecules in all biological systems and serve numerous essential cellular functions. The global analysis of complex lipids is very challenging due to the extreme diversity in lipid structures. Variation in linkages and positions of fatty acyl chain(s) on the lipid backbone, functional group modification, occurrence of the molecular species as isomers or isobars are among some of the greatest challenges to resolve in lipidomics. In this work, we describe a routine analytical approach combining two liquid chromatography platforms: hydrophilic interaction (HILIC) and C30 reversed-phase chromatography (C30RP) coupled to high resolution mass spectrometry (HRMS) as complementary high throughput platforms to analyze complex lipid mixtures. Vascular plants (kale leaves and corn roots), rat brain and soil microbes were used as proxies to evaluate the efficiency of the enhanced approach to resolve traditional, as well as, modified lipids during routine lipidomics analysis. We report for the first time, the observation of a modified class of acylphosphatidylglycerol (acylPG) in corn roots by HILIC, and further resolution of the isomers using C30RP chromatography. We also used this approach to demonstrate the presence of high levels of N-monomethyl phosphatidylethanolamine (MMPE) in soil microbes, as well as to determine the regioisomers of lysophospholipids in kale leaves. Additionally, neutral lipids were demonstrated using C30RP chromatography in positive ion mode to resolve triacylglycerol isomers in rat brain. The work presented here demonstrates how the enhanced approach can more routinely permit novel biomarker discovery, or lipid metabolism in a wide range of biological samples.

Moose and Caribou as Novel Sources of Functional Lipids: Fatty Acid Esters of Hydroxy Fatty Acids, Diglycerides and Monoacetyldiglycerides.

Fatty acid esters of hydroxy fatty acids (FAHFA), diglycerides (DG) and monoacetyldiglycerides (MAcDG) are gaining interest as functional lipids in pharmaceuticals and functional food formulations for managing and treating metabolic or inflammatory diseases. Herein, we investigated whether the antler and/or meat of two Cervids (moose and caribou) are novel sources of FAHFA, DG and MAcDG. We observed FAHFA present in moose and caribou composed mainly of polyunsaturated families, and that the esterification occurred frequently at the C5-hydroxy fatty acid moiety, most noticeably arachidonic acid 5-hydroxyeicosatrienoic acid (ARA-5-HERA). Moose antler, caribou and moose meat also contained significant levels of both 1,2-DG and 1,3-DG lipids. The 1,3-DG molecular species consisted mainly of 16:0/18:1, 18:0/16:0, and 18:0/18:1. On the other hand, major 1,2-DG species consisted of DG 18:0/18:0, 16:0/16:0 and 18:1/18:1 molecular species with higher levels in the antler compared to the meat. The molecular species composition of MAcDG was very simple and consisted of 14:2/18:2/2:0, 16:0/18:2/2:0, 16:0/18:1/2:0 and 18:0/18:1/2:0 with the first species 14:2/18:2/2:0 predominating in the tip of moose antlers. Increasing access to and knowledge of the presence of these functional lipids in foods will enhance their intake in the diet with potential implications in improving personal and population health.