Maternal Dietary Fish Oil Influences the Adipose Transcriptome in Offspring
Mihelic, R, R. Beckford, M. Huff, M. E. Staton, S. Das, J. Wilson, and B. H. Voy.  2018.  FASEB Journal, Vol. 32, No. 1_supplement April 2018.

Abstract:
Fish oil and other sources of dietary long chain n-3 polyunsaturated fatty acids (LC n-3 PUFA) reduce adiposity in animal models and humans. Recent epidemiological studies have associated a relatively high ratio of maternal n-3: n-6 PUFA with reduced adiposity in children, suggesting that maternal dietary fatty acids may be used to attenuate early childhood obesity. We developed an avian model (broiler chickens) to directly test the hypothesis that enriching the developing embryo in LC n-3 PUFA reduces adipose deposition after birth (hatch). We used broiler chickens because they are a model of polygenic susceptibility to obesity, and because the yolk (from which the embryo derives all of its lipids) can be controlled through the maternal diet. Using this model, we recently reported that enriching the maternal diet in fish oil (FO) reduced adiposity, promoted the formation of small adipocytes, and suppressed gluconeogenic proteins in adipose tissue of chicks compared to dietary corn oil (CO; Beckford et al., Sci Rep. 2017 Oct 13;7(1):13129). The objective of the current study was to identify potential mechanisms for these effects by using RNA sequencing to characterize the adipose transcriptomes of offspring from FO- and CO-fed hens. Broiler-breeder hens were fed diets with fat (2% of kcals) supplied from FO or CO for four weeks, after which fertilized eggs were collected and hatched. After hatch, all chicks were fed a CO-based diet. Transcriptomes were profiled in abdominal adipose tissue at 7 and 14 d of age (n=5/group). Differentially expressed genes (CO vs. FO) were analyzed for GO and KEGG pathway annotations using DAVID (https://david.ncifcrf.gov). At 7 days of age, 236 genes were differentially expressed between CO and FO diets (adj. p-value ≤ 0.05). Maternal FO significantly affected expression of a cluster of genes associated with lipid and glucose metabolism, including fatty acid binding protein 1 (FABP1), liver basic fatty acid binding protein (LBFABP), fructose-1,6-bisphosphatase 2 (FBP2), protein kinase, AMP-activated, alpha 2 catalytic subunit (PRKAA2), glucagon (GCG), and glucagon receptor-like protein (LOC772096). Differentially expressed genes were also significantly enriched in GO terms related to muscle cell development (adj. p-value<0.001). By 14 days, fewer genes (N=45) differed significantly between FO and CO chicks, although effects of the maternal diet on lipid metabolism persisted. In particular, expression of FABP1 remained upregulated (~ 4-fold) in FO vs. CO chicks at both ages, suggesting sustained influence of maternal dietary fat source on chick lipid metabolism. Interestingly, several of the differentially expressed genes, including insulin like growth factor 2 receptor (IGF2R), purinergic receptor P2RY1 (P2RY1), PRKAA2, phosphoglycerate dehydrogenase (PHGDH), and ankyrin repeat domain 1 (ANKRD1) have been shown to be methylated in response to the maternal diet and associated with offspring body composition in other species. In conclusion, these results indicate that maternal dietary fish oil influences multiple pathways, potentially through epigenetic modification, to reduce adipose deposition in offspring.