(LB02-24-25) Effect of Maternal Methyl-Donor Nutrients Supplementation to an Obesogenic Diet on Hepatic Lipolytic Gene Expression and Trimethylamine N-oxide Among Offspring

Objectives: Maternal obesogenic diet increases the risk of long-lasting metabolic dysfunction in the offspring. The role of perinatal nutrition in programming offspring metabolic features may be mediated by maternal dietary methyl-donor nutrients (MDN) intake. However, emerging evidence linked some MDN (eg, choline, betaine) intake to trimethylamine N-oxide (TMAO), a risk factor of cardiometabolic diseases, yet conclusive biochemical molecular evidence remained elusive. This study aims to examine the effect of MDN supplementation to an obesogenic diet during pregnancy and lactation on hepatic lipolytic gene expression and TMAO levels among offspring.

Methods: After mating, 10-week-old female Sprague-Dawley rats (n = 10/group) were randomly assigned to four dietary groups during pregnancy and lactation: (1) Control diet (AIN-93G) (CON), (2) CON with methyl-donor nutrients supplimentation (CON-MS), (3) High-fat, high-sucrose diet (HFS), and (4) HFS with MS (HFS-MS). MS includes folic acid (15 mg/kg), betaine (15 mg/kg), choline (11.2 mg/kg), vitamin B12 (1.5 mg/kg), L-methionine (7.5 mg/kg), and zinc (34.1 mg/kg). After waning, offspring (n = 10/sex/group) were randomly assigned to the HFS diet or CON diet for 12 weeks. Lipid biochemical indices, serum TMAO levels, and hepatic gene expression of PPARa, CPT1A and FMO3 were assayed.

Results: HFS feeding led to higher serum LDL and triglyceride levels, and lower serum HDL levels in male offsprings exposed to HFS diet after weaning, which were reduced in HFS-MS/HFS male offsprings (each P < 0.05). HFS/HFS feeding, but not HFS-MS/HFS feeding, led to an increase of serum TMAO levels in offsprings (P < 0.05), compared with the CON/CON diet. mRNA levels of hepatic CPT1A gene and the transcription factor PPARa that favors lipolysis were upregulated, whereas FMO3 gene encoding the enzyme for TMAO production was downregulated (each P < 0.05) by maternal MS to HFS feeding in male offspring fed with HFS diet.

Conclusions: Maternal methyl-donor nutrients supplementation reverse the adverse effects of the obesogenic diet on promoting lipid disorders in male offspring rats partially through upregulating hepatic PPARα/ CPT1A pathway without increasing serum TMAO levels.

Funding Sources: Texas State University Faculty Start-up Funding