Maternal high-fat diet triggers lipotoxicity in the fetal livers of nonhuman primates.

Abstract

Maternal obesity is thought to increase the offspring's risk of juvenile obesity and metabolic diseases; however, the mechanism(s) whereby excess maternal nutrition affects fetal development remain poorly understood. Here, we investigated in nonhuman primates the effect of chronic high-fat diet (HFD) on the development of fetal metabolic systems. We found that fetal offspring from both lean and obese mothers chronically consuming a HFD had a 3-fold increase in liver triglycerides (TGs). In addition, fetal offspring from HFD-fed mothers (O-HFD) showed increased evidence of hepatic oxidative stress early in the third trimester, consistent with the development of nonalcoholic fatty liver disease (NAFLD). O-HFD animals also exhibited elevated hepatic expression of gluconeogenic enzymes and transcription factors. Furthermore, fetal glycerol levels were 2-fold higher in O-HFD animals than in control fetal offspring and correlated with maternal levels. The increased fetal hepatic TG levels persisted at P180, concurrent with a 2-fold increase in percent body fat. Importantly, reversing the maternal HFD to a low-fat diet during a subsequent pregnancy improved fetal hepatic TG levels and partially normalized gluconeogenic enzyme expression, without changing maternal body weight. These results suggest that a developing fetus is highly vulnerable to excess lipids, independent of maternal diabetes and/or obesity, and that exposure to this may increase the risk of pediatric NAFLD.

• Authors: Carrie E McCurdy, Jacalyn M Bishop, Sarah M Williams, Bernadette E Grayson, M Susan Smith, Jacob E Friedman, Kevin L Grove
• Journal: The Journal of clinical investigation (J Clin Invest) Vol. 119 Issue 2 Pg. 323-35 (Feb 2009) ISSN: 0021-9738 [Print] United States
• PMID: 19147984 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Cytokines
• Dietary Fats
• Leptin
• Triglycerides

Topics

• Animals
• Cytokines (blood)
• Dietary Fats (adverse effects)
• Fatty Liver (etiology)
• Female
• Fetal Development
• Fetus (metabolism)
• Gluconeogenesis
• Glucose Tolerance Test
• Insulin Resistance
• Leptin (blood)
• Liver (metabolism)
• Macaca
• Male
• Maternal Nutritional Physiological Phenomena
• Obesity (complications)
• Oxidative Stress
• Pregnancy
• Triglycerides (metabolism)