Offspring susceptibility to metabolic alterations due to maternal high-fat diet and the impact of inhaled ozone used as a stressor

Abstract

The influence of maternal high-fat diet (HFD) on metabolic response to ozone was examined in Long-Evans rat offspring. F0 females were fed control diet (CD; 10%kcal from fat) or HFD (60%kcal from fat) starting at post-natal day (PND) 30. Rats were bred on PND 72. Dietary regimen was maintained until PND 30 when all offspring were switched to CD. On PND 40, F1 offspring (n = 10/group/sex) were exposed to air or 0.8 ppm ozone for 5 h. Serum samples were collected for global metabolomic analysis (n = 8/group/sex). Offspring from HFD dams had increased body fat and weight relative to CD. Metabolomic analysis revealed significant sex-, diet-, and exposure-related changes. Maternal HFD increased free fatty acids and decreased phospholipids (male > female) in air-exposed rats. Microbiome-associated histidine and tyrosine metabolites were increased in both sexes, while 1,5-anhydroglucitol levels decreased in males indicating susceptibility to insulin resistance. Ozone decreased monohydroxy fatty acids and acyl carnitines and increased pyruvate along with TCA cycle intermediates in females (HFD > CD). Ozone increased various amino acids, polyamines, and metabolites of gut microbiota in HFD female offspring indicating gut microbiome alterations. Collectively, these data suggest that maternal HFD increases offspring susceptibility to metabolic alterations in a sex-specific manner when challenged with environmental stressors.

Perinatal High-Fat Diet Influences Ozone-Induced Responses on Pulmonary Oxidant Status and the Molecular Control of Mitophagy in Female Rat Offspring

“…These results suggest that female offspring from dams fed an HFD experienced more detrimental effects from ozone exposure than the other offspring groups. This is in accordance with our previous study [19], which found ozone-induced changes in the gut microbiome metabolites and metabolites indicative of mitochondrial stress in tissues to be more profound in these same female offspring from HFD dams than other offspring groups. For males, the ozone effects did not differ between the offspring from CD or HFD dams.…”

“…We previously showed that the perinatal HFD compared with the CD increased the body weight and fat percentage of dams throughout gestation, as well as of the offspring at postnatal day (PND) 37 [ 18 , 19 ]. Furthermore, acute ozone exposure was shown to cause pulmonary protein leakage and lung cell injury in both female and male offspring, and induced neutrophilic inflammation in female offspring [ 19 ].…”

“…We previously showed that the perinatal HFD compared with the CD increased the body weight and fat percentage of dams throughout gestation, as well as of the offspring at postnatal day (PND) 37 [ 18 , 19 ]. Furthermore, acute ozone exposure was shown to cause pulmonary protein leakage and lung cell injury in both female and male offspring, and induced neutrophilic inflammation in female offspring [ 19 ]. We next studied whether these ozone-induced pulmonary responses in offspring were associated with alterations in oxidative stress markers and whether these responses were affected by maternal diet.…”

“…All of the markers were assessed within two hours after exposure to filtered air or ozone in the lungs or BALF from female and male offspring from dams fed a perinatal control diet (CD) or HFD. BALF albumin and total protein data were previously published [19]. Only significant correlations (q < 0.05) are shown in this table.…”

“…So far, two studies have shown that ozone-induced detrimental effects on lung function, injury, and inflammation in rat offspring were more profound in the offspring from dams that were fed a HFD diet during gestation [ 17 , 18 ]. Furthermore, a study deploying a systemic metabolomics approach demonstrated that a perinatal HFD exacerbated ozone-induced effects on lipid, protein, and energy metabolism, which suggested an impairment of mitochondrial function [ 19 ]. To elucidate whether mitochondria and changes in the molecular machinery that control the mitochondrial content and function are involved in the effect of maternal obesity on ozone susceptibility in offspring, we performed an experiment in which female rats were fed a HFD before and during gestation, and during lactation, after which the offspring were exposed to ozone at a young-adult age (forty days).…”