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).

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

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

  1. Data are summarized from the metabolomics report on ozone-induced changes in serum metabolites in young male and female offspring (n = 8/group) from dams that were fed CD or  HFD. ↑ indicates increase in metabolite levels, ↓ indicates decrease in metabolite levels, and → indicates no change in metabolite levels.
  2. PUFAs polyunsaturated fatty acids, TCA cycle tricarboxylic cycle, BCAA branched-chain amino acids, MTA methylthioadenosine, NAD nicotinamide adenine, 7-HOCA 7-alpha-hydroxy-3-oxo-4-cholestenoate.