Omega-3 polygenic score protects against altered eating behavior in intrauterine growth-restricted children.

BACKGROUND: Alterations in eating behavior are common in infants with intrauterine growth restriction (IUGR); omega-3 polyunsaturated fatty acids (PUFA) could provide protection. We hypothesized that those born IUGR with a genetic background associated with increased production of omega-3-PUFA will have more adaptive eating behaviors during childhood. METHODS: IUGR/non-IUGR classified infants from MAVAN and GUSTO cohorts were included at the age of 4 and 5 years, respectively. Their parents reported child's eating behaviors using the child eating behavior questionnaire-CEBQ. Based on the GWAS on serum PUFA (Coltell 2020), three polygenic scores were calculated. RESULTS: Significant interactions between IUGR and polygenic score for omega-3-PUFA on emotional overeating (ß = -0.15, P = 0.049 GUSTO) and between IUGR and polygenic score for omega-6/omega-3-PUFA on desire to drink (ß = 0.35, P = 0.044 MAVAN), pro-intake/anti-intake ratio (ß = 0.10, P = 0.042 MAVAN), and emotional overeating (ß = 0.16, P = 0.043 GUSTO) were found. Only in IUGR, a higher polygenic score for omega-3-PUFA associated with lower emotional overeating, while a higher polygenic score for omega-6/omega-3-PUFA ratio was associated with a higher desire to drink, emotional overeating, and pro-intake/anti-intake. CONCLUSION: Only in IUGR, the genetic background for higher omega-3-PUFA is associated with protection against altered eating behavior, while the genetic score for a higher omega-6/omega-3-PUFA ratio is associated with altered eating behavior. IMPACT: A genetic background related to a higher polygenic score for omega-3 PUFA protected infants born IUGR against eating behavior alterations, while a higher polygenic score for omega-6/omega-3 PUFA ratio increased the risk of having eating behavior alterations only in infants born IUGR, irrespective of their adiposity in childhood. Genetic individual differences modify the effect of being born IUGR on eating outcomes, increasing the vulnerability/resilience to eating disorders in IUGR group and likely contributing to their risk for developing metabolic diseases later in life.

Diminished insulin sensitivity is associated with altered brain activation to food cues and with risk for obesity - Implications for individuals born small for gestational age.

While classically linked to memory, the hippocampus is also a feeding behavior modulator due to its multiple interconnected pathways with other brain regions and expression of receptors for metabolic hormones. Here we tested whether variations in insulin sensitivity would be correlated with differential brain activation following exposure to palatable food cues, as well as with variations in implicit food memory in a cohort of healthy adolescents, some of whom were born small for gestational age (SGA). Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) was positively correlated with activation in the cuneus, and negatively correlated with activation in the middle frontal lobe, superior frontal gyrus and precuneus when presented with palatable food images versus non-food images in healthy adolescents. Additionally, HOMA-IR and insulinemia were higher in participants with impaired food memory. SGA individuals had higher snack caloric density and greater chance for impaired food memory. There was also an interaction between the HOMA-IR and birth weight ratio influencing external eating behavior. We suggest that diminished insulin sensitivity correlates with activation in visual attention areas and inactivation in inhibitory control areas in healthy adolescents. Insulin resistance also associated with less consistency in implicit memory for a consumed meal, which may suggest lower ability to establish a dietary pattern, and can contribute to obesity. Differences in feeding behavior in SGA individuals were associated with insulin sensitivity and hippocampal alterations, suggesting that cognition and hormonal regulation are important components involved in their food intake modifications throughout life.