Maternal omega-3 fatty acid deficiency affects fetal thermogenic development and postnatal musculoskeletal growth in mice

Abstract

Maternal omega-3 (n-3) polyunsaturated fatty acids (PUFAs) deficiency can affect offsprings adiposity and metabolism by modulating lipid and glucose metabolism. However, the impact of n-3 PUFA deficiency on the development of fetal thermogenesis and its consequences is not reported. Using an n-3 PUFA deficient mice, we assessed fetal interscapular brown adipose tissue (iBAT), body fat composition, insulin growth factor-1 (IGF-1), glucose transporters (GLUTs), and expression of lipid storage & metabolic proteins in the offspring. The n-3 PUFA deficiency did not change the pups calorie intake, organ weight, and body weight. However, the offsprings skeletal growth was altered due to excess fat to lean mass, reduced tibia & femur elongation, dysregulated IGF-1 in the mother and pups (p<0.05). Localization of uncoupling protein 1 (UCP1) in iBAT exhibited a reduced expression in the deficient fetus. Further, UCP1, GLUT1, GPR120 were downregulated while FABP3, ADRP, GLUT4 expressions were upregulated in the BAT of the deficient offspring (p<0.05). The deficiency decreased endogenous conversion of the n-3 LCPUFAs from their precursors and upregulated SCD1, FASN, and MFSD2A mRNAs in the liver (p<0.05). An altered musculoskeletal growth in the offspring is associated with impaired browning of the fetal adipose, dysregulated thermogenesis, growth hormone, and expression of glucose and fatty acid metabolic mediators due to maternal n-3 PUFA deficiency. BAT had higher metabolic sensitivity compared to WAT in n-3 PUFA deficiency. Maternal n-3 PUFA intake may prevent excess adiposity by modulating fetal development of thermogenesis and skeletal growth dynamics in the mice offspring. HighlightO_LIMaternal n-3 PUFA deficiency dysregulated the development of fetal adipose browning C_LIO_LIN-3 PUFA regulates fetal thermogenic development by altering UCP1 expression C_LIO_LIBAT had higher metabolic sensitivity compared to WAT in n-3 PUFA deficiency C_LIO_LIIncreased fat mass and IGF-1 played a role in promoting adiposity in n-3 PUFA deficiency C_LI