Alpha linolenic acid in maternal diet halts the lipid disarray due to saturated fatty acids in the liver of mice offspring at weaning

Abstract

BackgroundAlpha linolenic acid (ALA, 18:3) in maternal diets has been shown to attenuate obesity associated insulin resistance (IR) in adult offspring in mice. The objective in the present study was to detect the early effects of maternal dietary saturated fatty acids (SFA) and their partial substitution with ω-3 ALA, docosa hexenoic acid (DHA,22:6) and eicosapentenoic acid 20:5 (EPA,20:5) on the HOMA index, liver lipids and fatty acid desaturases in the offspring at weaning.Methods3 month old C57Bl6/J female mice were fed diets containing normal amount of calories but rich in SFA alone or partially replaced with ALA, DHA or EPA before mating, during pregnancy and lactation.ResultsPregnant mice fed SFA produced offspring with the highest HOMA index, liver lipids and desaturase activities. ALA prevented SFA induced lipid increase but DHA and EPA only reduced it by 42% and 31% respectively. ALA, DHA and EPA decreased HOMA index by 84%, 75% and 83% respectively. ALA, DHA and EPA decreased Δ6 and SCD1 desaturase activities about 30%.ConclusionsSFA feeding to mothers predisposes their offspring to develop IR and liver lipid accumulation already at weaning. ω3 fatty acids reduce IR, ALA halts lipid accumulation whereas DHA and EPA only blunt it.ALA and DHA restore the increased SCD1 to normal. These studies suggest that ω-3 fatty acids have different potencies to preclude lipid accumulation in the offspring partially by affecting pathways associated to SCD1 modulation.

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

“…PLIN5 is a lipid droplet-targeting protein [18] that promotes the association of lipid droplets with mitochondria and contributes to the prevention of the accumulation of intracellular triglyceride, playing an important protective role against hepatic lipotoxicity induced by free FA generated by lipolysis [19]. The present findings may explain our previous results showing a preventive effect of ALA in hepatosteatosis in the offspring at weaning and in adult life after a high-fat diet challenge [4,5]. …”

“…Moreover, ALA upregulated whilst SFA downregulated Per3 expression. These profound differences may account for the opposite healthy or obese associated phenotype developed by offspring of ALA- or SFA-fed mothers, respectively, described previously by us [4,5]. …”

“…These findings enhance the relevance of our results, pointing to the maternal SFA ‘per se' independent of excess fat, in the programming of chronic disease in the offspring. ALA-enriched diet prevented those symptoms [4,5]. …”

“…Lipids were extracted from an aliquot of the liver homogenate as previously described [4,5]. Liver lipid FA were analyzed as FA methyl ester derivatives by gas chromatography in a Varian 3800 Series (Walnut Creek, Calif., USA) chromatograph (FID) with a fused silica SGE capillary column (30 × 0.025) and quantified using the Varian Star Workstation Advance Application software version 6x.…”

“…Moreover, the effects of the essential ω-3 α-linolenic acid (ALA), in particular, have seldom been considered. We have lately demonstrated that ALA or saturated fatty acids (SFA) prevent or promote, respectively, liver fat accumulation, metabolic disarray and insulin resistance in the weaning [4] and in the adult mice offspring challenged with a high-fat diet (HFD) [5]. We hypothesize that ALA and SFA enrichment in maternal nutrition, independent of the amount of calories, induce differential long-lasting gene expression patterns in the offspring, programming a divergent fat-associated metabolic phenotype and susceptibility to diet-induced obesity.…”