Is there A Role for Alpha-Linolenic Acid in the Fetal Programming of Health?

The role of ω3 alpha linolenic acid (ALA) in the maternal diet during pregnancy and lactation, and its effect on the prevention of disease and programming of health in offspring, is largely unknown. Compared to ALA, ω3 docosahexaenoic (DHA) and eicosapentaenoic (EPA) acids have been more widely researched due to their direct implication in fetal neural development. In this literature search we found that ALA, the essential ω3 fatty acid and metabolic precursor of DHA and EPA has been, paradoxically, almost unexplored. In light of new and evolving findings, this review proposes that ALA may have an intrinsic role, beyond the role as metabolic parent of DHA and EPA, during fetal development as a regulator of gene programming for the prevention of metabolic disease and promotion of health in offspring

How Alpha Linolenic Acid May Sustain Blood–Brain Barrier Integrity and Boost Brain Resilience against Alzheimer’s Disease

Cognitive decline, the primary clinical phenotype of Alzheimer’s disease (AD), is currently attributed mainly to amyloid and tau protein deposits. However, a growing body of evidence is converging on brain lipids, and blood–brain barrier (BBB) dysfunction, as crucial players involved in AD development. The critical role of lipids metabolism in the brain and its vascular barrier, and its constant modifications particularly throughout AD development, warrants investigation of brain lipid metabolism as a high value therapeutic target. Yet, there is limited knowledge on the biochemical and structural roles of lipids in BBB functionality in AD. Within this framework, we hypothesize that the ApoE4 genotype, strongly linked to AD risk and progression, may be related to altered fatty acids composition in the BBB. Interestingly, alpha linolenic acid (ALA), the precursor of the majoritarian brain component docosahexaenoic acid (DHA), emerges as a potential novel brain savior, acting via BBB functional improvements, and this may be primarily relevant to ApoE4 carriers

Fatty acid bile acid conjugates (FABACs)—New molecules for the prevention of cholesterol crystallisation in bile

BACKGROUND—Cholesterol gall stones are a frequent disease for which at present surgery is the usual therapy. Despite the importance of bile acids it has become evident that phospholipids are the main cholesterol solubilisers in bile. Even phospholipid components, such as fatty acids, have anticrystallising activity.
AIM—To synthesise fatty acid bile acid conjugates (FABACs) and study their effects on cholesterol crystallisation in bile in vitro and in vivo.
METHODS—FABACs were prepared by conjugation of cholic acid at position 3 with saturated fatty acids of variable chain length using an amide bond. Cholesterol crystallisation and its kinetics (crystal observation time, crystal mass) were studied in model bile, pooled enriched human bile, and fresh human bile using FABACs with saturated fatty acids of varying chain length (C-6 to C-22). Absorption of FABACs into blood and bile was tested in hamsters. Prevention of biliary cholesterol crystallisation in vivo was tested in hamsters and inbred mice.
RESULTS—FABACs strongly inhibited cholesterol crystallisation in model as well as native bile. The FABACs with longer acyl chains (C-16 to C-22) were more effective. At a concentration of 5 mM, FABACs almost completely inhibited cholesterol crystallisation in fresh human bile for 21 days. FABACs were absorbed and found in both portal and heart blood of hamsters. Levels in bile were 2-3 times higher than in blood, indicating active secretion. Appreciable levels were found in the systemic circulation 24-48 hours after a single administration. Ingested FABACs completely prevented the formation of cholesterol crystals in the gall bladders of hamsters and mice fed a lithogenic diet.
CONCLUSIONS—FABACs are potent inhibitors of cholesterol crystallisation in bile. They are absorbed and secreted into bile and prevent the earliest step of cholesterol gall stone formation in animals. These compounds may be of potential use in cholesterol gall stone disease in humans.


Keywords: gall stones; bile; phospholipids; cholesterol crystallisation; fatty acid bile acid conjugate

Supplementary Material for: Maternal Diet Enriched with α-Linolenic or Saturated Fatty Acids Differentially Regulates Gene Expression in the Liver of Mouse Offspring

<p><b><i>Background/Aims:</i></b> Lipid metabolic disarray in the liver of young and adult mice offspring is induced by saturated fatty acids (SFA) but prevented by α-linolenic acid (ALA, 18:3 ω-3) in the maternal diet during pregnancy and lactation. The aim of the present study was to analyze the impact of maternal dietary ALA compared to an SFA diet on the liver gene expression in the newborn offspring. <b><i>Methods:</i></b> C57Bl6/J dams were fed with diets normal in calories but rich in ALA or SFA before mating and during pregnancy. Pups were sacrificed at birth and liver parameters were assessed. Gene expression was characterized by microarray analysis and validated by real-time quantitative PCR. <b><i>Results:</i></b> ALA, compared to SFA, in maternal diets during pregnancy increased polyunsaturated fatty acids, while it differentially modified fatty acid desaturase activities in offspring liver. Overall, 474 and 662 genes from the liver of newborn pups were differentially regulated by ALA and SFA compared to control diet (p < 0.05; fold change 2), respectively. Notably, Per3 was upregulated by ALA, whereas it was downregulated by SFA, compared to control diet. <b><i>Conclusions:</i></b> ALA- and SFA-enriched diets differentially affect the gene expression pattern in the offspring's liver. ALA, in particular, upregulates genes associated with low adiposity.</p