Table 3 Summary of major ozone-related changes in serum metabolites in young male and female offspring from dams fed control diet (CD) or high-fat diet (HFD).
Female ozone effect | Male ozone effect | Interpretation |
|---|---|---|
Lipid metabolism | ||
↓ in diet-derived PUFAs (i.e., linoleate and linolenate) in HFD group ↓ in short and medium chain fatty acids in both CD and HFD and in long-chain fatty acids in HFD groups ↓ in acyl carnitines (HFD > CD) ↓ in hydroxyl fatty acids ↑ in odd chain decarboxylates ↓ in even chain decarboxylates | ↑ in PUFAs (i.e., DHA and arachidonate) (CD > HFD) ↓ in short and medium chain fatty acids (fewer than females) in both CD and HFD ↓ in acyl carnitines only in CD group ↑ in odd chain decarboxylates | ↑ in breakdown of membrane phospholipids ↓ in desaturase activity ↓ in beta-oxidation (mitochondria) ↑ in omega-oxidation (peroxisomes) Mitochondrial impairment and compensation by omega-oxidation in peroxisomes Sex-specific differences in ozone effects on beta-oxidation and TCA cycle |
Energy metabolism | ||
→ in glucose ↑ in pyruvate ↑ in TCA cycle intermediates (HFD > CD) | ↑ in glucose | ↑ in glucose production and/or ↓ in insulin secretion in males after ozone exposure ↑ in glycolysis and TCA cycle in females after ozone exposure (HFD > CD) |
↑ in BCAA catabolites ↑ in ethylmalonate | ↑ in BCAA catabolites | ↑ use of BCAA for energy and/or impairment in mitochondrial function in both sexes after ozone exposure |
Nitrogen balance | ||
↑ in acetylated amino acids (HFD > CD) ↑ in urea in CD ↑ in polyamines and MTA (HFD > CD) | ↑ in acetylated amino acids (HFD > CD) ↑ in urea in the HFD group ↑ in polyamines | ↑ in protein degradation by ozone exposure Alternations in nitrogen balance (HFD > CD) ↑ in activation of protective mechanisms (DNA stability, cell differentiation, and proliferation) |
Tryptophan and NAD metabolism | ||
↑ in kynurenine and downstream metabolites | ↑ in kynurenine and xanthurenate in HFD group | Kynurenine, produced from tryptophan, serves to downregulate inflammation and is an intermediate for NAD synthesis, thus increases might indicate increased energetics and signal transduction |
Steroid metabolism | ||
↑ in 7-HOCA and 7-hydroxycholesterol ↓ pregnanolone/ allopregnanolone sulfate | ↑ in 7-HOCA | Ozone may affect a P450 family of enzymes involved in steroid metabolism and change bile acids synthesis Differences in females’ progestin steroids may suggest ozone effect on hypothalamic–pituitary–adrenal axis |
↓ Biliverdin and bilirubin (CD > HFD) | ↓ Biliverdin and bilirubin (CD > HFD) | Reactive oxygen species levels are likely high in ozone-exposed rats (CD) |
Microbiome | ||
↑ Benzoate metabolites (carboxylates) by ozone (HFD > CD) | Potential change in gut microbiome after ozone exposure in females | |