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Programmed aortic dysfunction and reduced Na+,K+-ATPase activity present in first generation offspring of lard-fed
James A Armitage1, Asuka Ishibashi, Aswini A Balachandran
1Maternal and Fetal Research Unit, Division of Reproduction and Endocrinology, King's College London, 10th Floor North Wing, St Thomas' Hospital, Lambeth Palace Road, London SE1 7EH, UK.
Insights
Maternal high-fat (OHF) diet did not transmit cardiovascular dysfunction to the F(2) generation. Offspring showed normal vascular function and renal Na(+),K(+)-ATPase activity, indicating no intergenerational effects.
Area of Science:
- Cardiovascular Physiology
- Developmental Programming
- Nutritional Science
Background:
- Maternal high-fat (OHF) diet in Sprague-Dawley rats causes cardiovascular dysfunction in F(1) offspring.
- Cardiovascular dysfunction can be transmitted across generations in some developmental programming models.
- Previous studies reported blunted vasodilation and reduced renal Na(+),K(+)-ATPase activity in F(1) offspring.
Purpose of the Study:
- To investigate the transgenerational effects of a maternal high-fat (lard) diet on cardiovascular function and renal Na(+),K(+)-ATPase activity in F(2) offspring.
- To determine if cardiovascular dysfunction observed in the F(1) generation is inherited by the F(2) generation.
- To assess vascular responses and renal enzyme activity in F(2) Sprague-Dawley rats exposed prenatally and postnatally to a maternal high-fat diet.
Main Methods:
- Isolated aortic rings from 6-month-old male and female F(2) offspring (n=13 per group) were used to assess vascular function in an organ bath.
- Phenylephrine-induced constrictor responses and acetylcholine-induced endothelium-dependent dilator responses were measured.
- Passive distensibility and renal Na(+),K(+)-ATPase activity were evaluated in F(2) offspring from lard-fed (OHF) and control-fed (OC) dams.
- Statistical analysis included repeated measures ANOVA and ANOVA.
Main Results:
- Female F(2) offspring of lard-fed dams exhibited increased brain and kidney weights compared to controls (P < 0.03).
- No significant differences were observed in aortic constrictor responses to phenylephrine (P = 0.85), endothelium-dependent dilation to acetylcholine (P = 0.96), or passive distensibility (P = 0.68) between groups.
- Renal Na(+),K(+)-ATPase activity in F(2) offspring was not statistically different from control animals (P = 0.89).
Conclusions:
- A maternal diet rich in animal fat (lard) does not appear to transmit cardiovascular dysfunction or altered renal Na(+),K(+)-ATPase activity to the F(2) generation.
- While the maternal high-fat diet had adverse effects on F(1) animals, these negative impacts were not observed in the F(2) offspring.
- This study suggests a lack of intergenerational transmission of the specific cardiovascular and renal alterations induced by the maternal high-fat diet.
Abstract:
We have previously reported that male and female offspring of Sprague-Dawley rats fed a diet rich (approximately 50% of caloric intake from fat) in animal fat (lard) during pregnancy and suckling (OHF) demonstrate cardiovascular dysfunction, including blunted endothelium-dependent vasodilatation in the aorta as well as reduced renal Na(+),K(+)-ATPase activity. Cardiovascular dysfunction has been reported in other models of developmental programming and some researchers describe transmission from F(1) to F(2) generations. Here we report a study of vascular function, as assessed in isolated rings of aorta mounted in an organ bath, and renal Na(+),K(+)-ATPase activity in 6-month-old male and female F(2) offspring of lard-fed and control-fed (OC) dams (n = 13 per diet group). An increase in brain (OC 0.61 +/- 0.01% versus OHF 0.66 +/- 0.02% of bodyweight) and kidney weights (OC 0.32 +/- 0.01% versus OHF 0.37 +/- 0.01% of bodyweight) was observed in female F(2) offspring of lard-fed dams compared with F(2) controls (P < 0.03). Constrictor responses to phenylephrine in the aorta were not different from F(2) controls (repeated measures ANOVA, P = 0.85). Also, endothelium-dependent dilator function, as assessed by responses to acetylcholine (repeated measures ANOVA, P = 0.96) and passive distensibility in the absence of extracellular calcium (repeated measures ANOVA, P = 0.68), was similar. Additionally, renal Na(+),K(+)-ATPase activity was not statistically different from that observed in control animals (ANOVA, P = 0.89). Although a maternal diet rich in animal fat has deleterious effects on parameters of cardiovascular risk in F(1) animals, it does not appear that disorders previously reported in the F(1) generation are transmitted to the F(2) generation.
