Abstract
Linoleic acid (LA), an essential n-6 fatty acid (FA), is critical for fetal development. We investigated the effects of maternal high LA (HLA) diet on offspring cardiac development and its relationship to circulating FA and cardiovascular function in adolescent offspring, and the ability of the postnatal diet to reverse any adverse effects. Female Wistar Kyoto rats were fed low LA (LLA; 1·44 % energy from LA) or high LA (HLA; 6·21 % energy from LA) diets for 10 weeks before pregnancy and during gestation/lactation. Offspring, weaned at postnatal day 25, were fed LLA or HLA diets and euthanised at postnatal day 40 (n 6-8). Maternal HLA diet decreased circulating total cholesterol and HDL-cholesterol in females and decreased total plasma n-3 FA in males, while maternal and postnatal HLA diets decreased total plasma n-3 FA in females. α-Linolenic acid (ALA) and EPA were decreased by postnatal but not maternal HLA diets in both sexes. Maternal and postnatal HLA diets increased total plasma n-6 and LA, and a maternal HLA diet increased circulating leptin, in both male and female offspring. Maternal HLA decreased slopes of systolic and diastolic pressure-volume relationship (PVR), and increased cardiac Col1a1, Col3a1, Atp2a1 and Notch1 in males. Maternal and postnatal HLA diets left-shifted the diastolic PVR in female offspring. Coronary reactivity was altered in females, with differential effects on flow repayment after occlusion. Thus, maternal HLA diets impact lipids, FA and cardiac function in offspring, with postnatal diet modifying FA and cardiac function in the female offspring.
Link to Full Text
Key Points
Linoleic acid (LA; 18:2n-6; cis, cis-9,12-octadecadienoic acid) is the most abundant n-6 PUFA in modern human diets. It can be elongated and desaturated to produce arachidonic acid (AA, 20:4n-6) a precursor of eicosanoid mediators such as PG, thromboxanes and leukotrienes, which influence inflammatory processes. In recent years, worldwide dietary guidelines have encouraged replacing animal-based SFA
with plant-based PUFA, the most abundant being LA. As a result, the current intake of LA is significantly higher than required to prevent deficiency. The excess in LA may decrease the ability of the n-3 PUFA α-linolenic acid (ALA), to produce longer chain anti-inflammatory n-3 PUFA such as EPA (20:5n-3) and DHA, as both are metabolised by the same enzymes, with the enzymes that metabolise LA and ALA having
a higher enzymatic affinity for LA. There is evidence from randomised control trials that a high LA and low SFA diet reduces cardiac events and mortality in post-infarct patients.
Rodent studies also support a role for the post-weaning diet on disease risk, with a study demonstrating
that a post-weaning obesogenic diet can exacerbate the detrimental effects of maternal diet-induced obesity on offspring body weight gain. The hypothesis of the present study was that a maternal diet high in LA would programme cardiovascular sex-specific deficits that will be reversed by a low LA diet following weaning. Both a maternal and a postnatal diet high in LA influence offspring plasma FA, lipid profiles and cardiac function in a sex-specific manner. These direct functional changes are associated with sex-specific changes in fibrogenic gene expression in male offspring in response to a HLA maternal diet. Further studies in adult offspring are warranted to explore how maternal and early postnatal intake of LA affect cardiovascular phenotype in adulthood.