Gestational fish oil supplementation in a high-fat diet induces sex-specific myokine changes in weanling offspring.

Previous research showed that a maternal high-fat (HF) diet during the perinatal period impairs skeletal muscle metabolism in offspring. Supplementing the HF diet with fish oil (FO), a source of n-3 polyunsaturated fatty acids, during gestation partially mitigates these adverse effects at weaning. This study investigated whether maternal HF diet, with or without FO supplementation during gestation, alters the expression of muscle-secreted molecules (myokines) in female and male offspring at weaning. Female Wistar rats were fed a control (9% lipids) or HF diet (29% lipids) for 8 weeks before mating and throughout gestation and lactation. A subset of HF-fed dams received a 3% FO-supplemented HF diet (HFFO) during gestation. In glycolytic extensor digitorum longus (EDL) muscle, FO tended to decrease Nmb (neuromedin B) mRNA in females and increased Erfe (myonectin) mRNA in males, compared to sex-matched HF groups. HFFO males also exhibited elevated expression of genes involved in fatty acid uptake and oxidation, suggesting enhanced lipid metabolism. However, FO did not reverse the HF-induced downregulation of Igf1r in EDL or Igf1 in the oxidative soleus muscle of male offspring, and muscle fiber size remained unchanged across groups. In the soleus muscle, FO increased Il6 mRNA in females, while in males, FO induced FNDC5 (the irisin precursor), accompanied by increased uncoupling protein-1 in subcutaneous white adipose tissue, suggesting increased thermogenic activity. Gestational FO supplementation induces sex- and muscle-specific alterations in myokine expression in weanling offspring exposed to a maternal HF diet, potentially shaping early muscle metabolism and contributing to sex-dependent metabolic programming.