Mechanisms for Programming Reduced Adiposity through Maternal Dietary Fish Oil
Authors: Beckford Ronique , Yu Jiali , Das Suchita , Hettich Robert , Wilson Jeanna , Voy Brynn 
Published: November 2023

Maternal diet and lifestyle can contribute to childhood obesity through sustained postnatal effects on adipose tissue growth and metabolism. 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. Epidemiological and experimental studies suggest that a relatively high ratio of maternal n‐3:n‐6 PUFA may also reduce adiposity in offspring. We developed an avian model to test the hypothesis that enriching developing adipose tissue in LC n‐3 PUFA programs offspring toward reduced adiposity. Tissue enrichment in specific fatty acids was achieved by feeding breeder hens diets with fat supplied as fish oil (FO) or corn oil (CO; each 2% of kcals). Both FO and CO chicks were fed a diet with fat supplied as CO from hatch to euthanasia at 7 or 14 days of age. As we previously reported, FO chicks had significantly reduced adiposity for both abdominal and subcutaneous depots (Beckford et al., FASEB J. v30(1) S124.1, 2016). Effects of diet persisted for at least 14 days of age, despite the fact that dietary fat was supplied exclusively as CO after hatch. The objective here was to identify potential mechanisms for reduced adiposity, using a combination of histology, QPCR, and LC‐MS/MS. Hen dietary lipid source significantly affected chick adipocyte size, with FO increasing abundance of small adipocytes at the expense of large adipocytes in both adipose depots (p<0.05). Adipose lipids of FO chicks were significantly enriched in eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) at 7 and 14 days of age (p<0.05), reflecting sustained effects of hen diet. Hen FO feeding also significantly enriched chick adipose tissue in myristic acid (14:0) a fatty acid associated with reduced adipocyte size and improved insulin sensitivity. QPCR revealed that expression of peroxisome proliferator activated receptor‐γ (PPAR‐γ) and PPAR‐γ coactivator 1B (PPARGC1B) was significantly increased in adipose tissue of FO vs. CO chicks (4.4‐ and 3.4‐fold, respectively), while FO down‐regulated expression of lipoprotein lipase by ~ 60% (p<0.05). Key genes for fatty acid synthesis (fatty acid synthase; Fasn) and oxidation (carnitine palmitoyl transferase 1 (Cpt1) and acyl‐coenzyme A oxidase 1 (Acox1) were not affected by diet in adipose or liver (p>0.05). Effects of FO on the abdominal adipose proteome were determined by LC‐MS/MS, using the UniProt database (uniprot.org) of Gallus gallus proteins to identify mass spectra. A total of 120 known proteins differed significantly between FO and CO chicks (p>0.05 and fold‐change ≥ 1.5). These were enriched in functions related to cytoskeletal organization (fdr p=3.6 E‐7), glycolysis (fdr p=0.021), and Ca2±transporting ATPase activity (fdr p=0.0024), among others (DAVID 6.8; david.ncifcrf.gov). In combination, these data suggest that maternal consumption of fish oil and potentially other sources of LC n‐3 PUFA reduces offspring adiposity by altering adipogenesis, metabolism and biophysical components of developing adipose tissue.

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University of Tennessee Center of Excellence in Livestock Diseases and Human Health