Infant Red Blood Cell Arachidonic to Docosahexaenoic Acid Ratio Inversely Associates with Fat-Free Mass Independent of Breastfeeding Exclusivity

The prevalence of childhood obesity has increased nearly ten times over the last 40 years, influenced by early life nutrients that have persistent effects on life-long metabolism. During the first six months, infants undergo accelerated adipose accumulation, but little is known regarding infant fatty acid status and its relationship to infant body composition. We tested the hypothesis that a low arachidonic to docosahexaenoic acid ratio (AA/DHA) in infant red blood cells (RBCs), a long-term indicator of fatty acid intake, would associate with more infant fat-free mass (FFM) and/or less adipose accumulation over the first 4 months of life. The fatty acid and composition of breastmilk and infant RBCs, as well as the phospholipid composition of infant RBCs, were quantified using targeted and unbiased lipid mass spectrometry from infants predominantly breastfed or predominantly formula-fed. Regardless of feeding type, FFM accumulation was inversely associated with the infant’s RBC AA/DHA ratio (p = 0.029, R2 = 0.216). Infants in the lowest AA/DHA ratio tertile had significantly greater FFM when controlling for infant sex, adiposity at 2 weeks, and feeding type (p < 0.0001). Infant RBC phospholipid analyses revealed greater peroxisome-derived ether lipids in the low AA/DHA group, primarily within the phosphatidylethanolamines. Our findings support a role for a low AA/DHA ratio in promoting FFM accrual and identify peroxisomal activity as a target of DHA in the growing infant. Both FFM abundance and peroxisomal activity may be important determinants of infant metabolism during development

Neonatal intake of Omega-3 fatty acids enhances lipid oxidation in adipocyte precursors

Summary: Establishing metabolic programming begins during fetal and postnatal development, and early-life lipid exposures play a critical role during neonatal adipogenesis. We define how neonatal consumption of a low omega-6 to −3 fatty acid ratio (n6/n3 FA ratio) establishes FA oxidation in adipocyte precursor cells (APCs) before they become adipocytes. In vivo, APCs isolated from mouse pups exposed to the low n6/n3 FA ratio had superior FA oxidation capacity, elevated beige adipocyte mRNAs Ppargc1α, Ucp2, and Runx1, and increased nuclear receptor NR2F2 protein. In vitro, APC treatment with NR2F2 ligand-induced beige adipocyte mRNAs and increased mitochondrial potential but not mass. Single-cell RNA-sequencing analysis revealed low n6/n3 FA ratio yielded more mitochondrial-high APCs and linked APC NR2F2 levels with beige adipocyte signatures and FA oxidation. Establishing beige adipogenesis is of clinical relevance, because fat depots with energetically active, smaller, and more numerous adipocytes improve metabolism and delay metabolic dysfunction