Acute and perinatal programming effects of a fat-rich diet on rat muscle mitochondrial function and hepatic lipid accumulation.

OBJECTIVE: Maternal high-fat intake during pregnancy may have long-term consequences in the offspring. Since this might relate to the capacity of mitochondrial metabolic adaptation and hepatic lipid metabolism, we investigated how maternal high-fat intake affected mitochondrial function and hepatic steatosis in the offspring. DESIGN: Sprague-Dawley rats were fed a high-fat (20% w/w) or a control diet (chow, C) from 10 days before pregnancy and throughout lactation. At weaning the litters were split into two groups; one was continued on the maternal diet and the other was fed low-fat chow. SAMPLE: Skeletal muscle mitochondria and liver lipids. METHODS: Mitochondrial respiration and hepatic lipid content were determined during and after weaning, on days 20 and 70 postpartum. MAIN OUTCOME MEASURES: Mitochondrial function and hepatic lipids. RESULTS: At 20 days, maternal high-fat diet caused increased Vo2max with pyruvate as substrate (p=0.047), at 70 days, pups born by C-dams, but not those born by high-fat-dams, showed increased oxidation of palmitoylcarnitine in the absence of ADP (p=0.018). Rates of ADP-stimulated oxygen consumption, maximal respiratory capacity and mitochondrial respiratory control ratio with pyruvate, increased post weaning (p<0.001), whereas respiratory control ratio with palmitoylcarnitine decreased (p=0.013). The increase in respiratory control ratio was most pronounced in pups from C-dams (p=0.05). The high-fat-diet caused pronounced hepatic steatosis in pups at weaning (p<0.001), without concomitant ceramide accumulation, while high-fat-feeding after weaning induced triacylglycerol and ceramide accumulation (p<0.01), regardless of maternal diet. CONCLUSION: Intake of a fat-rich diet during pregnancy and lactation reduced the age-induced increases in un-coupled fat oxidation.

Intake of whole apples or clear apple juice has contrasting effects on plasma lipids in healthy volunteers.

PURPOSE: Fruit consumption is associated with a decreased risk of CVD in cohort studies and is therefore endorsed by health authorities as part of the '5 or more a day' campaigns. A glass of fruit juice is generally counted as one serving. Fruit may cause protection by affecting common risk factors of CVD. METHODS: Apples are among the most commonly consumed fruits and were chosen for a comprehensive 5 × 4 weeks dietary crossover study to assess the effects of whole apples (550 g/day), apple pomace (22 g/day), clear and cloudy apple juices (500 ml/day), or no supplement on lipoproteins and blood pressure in a group of 23 healthy volunteers. RESULTS: The intervention significantly affected serum total and LDL-cholesterol. Trends towards a lower serum LDL-concentration were observed after whole apple (6.7%), pomace (7.9%) and cloudy juice (2.2%) intake. On the other hand, LDL-cholesterol concentrations increased by 6.9% with clear juice compared to whole apples and pomace. There was no effect on HDL-cholesterol, TAG, weight, waist-to-hip ratio, blood pressure, inflammation (hs-CRP), composition of the gut microbiota or markers of glucose metabolism (insulin, IGF1 and IGFBP3). CONCLUSIONS: Apples are rich in polyphenols and pectin, two potentially bioactive constituents; however, these constituents segregate differently during processing into juice products and clear juice is free of pectin and other cell wall components. We conclude that the fibre component is necessary for the cholesterol-lowering effect of apples in healthy humans and that clear apple juice may not be a suitable surrogate for the whole fruit in nutritional recommendations.

Maternal dietary supplementation with saturated, but not monounsaturated or polyunsaturated fatty acids, leads to tissue-specific inhibition of offspring Na+,K+-ATPase.

In rats, a maternal diet rich in lard is associated with reduced Na(+),K(+)-ATPase activity in adult offspring kidney. We have addressed the role of different fatty acids by evaluating Na(+),K(+)-ATPase activity in offspring of dams fed diets rich in saturated (SFA), monounsaturated (MUFA) or polyunsaturated (PUFA) fatty acids. Female Sprague-Dawley rats were fed, during pregnancy and suckling, a control diet (4% w/w corn oil) or a fatty acid supplemented diet (24% w/w). Offspring were reared on chow (4% PUFA) and studied at 6 months. mRNA expression (real-time PCR) of Na(+),K(+)-ATPase alpha subunit and protein expression of Na(+),K(+)-ATPase subunits (Western blot) were assessed in kidney and brain. Na(+),K(+)-ATPase activity was reduced in kidney (P < 0.05 versus all groups) and brain (P < 0.05 versus control and MUFA offspring) of the SFA group. Neither Na(+),K(+)-ATPase alpha1 subunit mRNA expression, nor protein expression of total alpha, alpha1, alpha2, alpha3 or beta1 subunits were significantly altered in kidney in any dietary group. In brains of SFA offspring alpha1 mRNA expression (P < 0.05) was reduced compared with MUFA and PUFA offspring, but not controls. Also in brain, SFA offspring demonstrated reduced (P < 0.05) alpha1 subunit protein and increased phosphorylation (P < 0.05) of the Na(+),K(+)-ATPase modulating protein phospholemman at serine residue 63 (S63 PLM). Na(+),K(+)-ATPase activity was similar to controls in heart and liver. In utero and neonatal exposure to a maternal diet rich in saturated fatty acids is associated with altered activity and expression of Na(+),K(+)-ATPase in adulthood, but mechanisms appear tissue specific.

An onion byproduct affects plasma lipids in healthy rats.

Onion may contribute to the health effects associated with high fruit and vegetable consumption. A considerable amount of onion production ends up as waste that might find use in foods. Onion byproduct has not yet been explored for potential health benefits. The aim of this study is to elucidate the safety and potential role of onion byproducts in affecting risk markers of cardiovascular disease (CVD). For that purpose, the effects of an onion byproduct, Allium cepa L. cepa 'Recas' (OBP), and its two derived fractions, an ethanolic extract (OE) and a residue (OR), on the distribution of plasma lipids and on factors affecting cholesterol metabolism in healthy rats have been investigated. The OBP or its fractions did not significantly reduce cholesterol or down-regulate hepatic 3-hydroxy-3-methylglutaryl-coenzyme A reductase (Hmgcr) gene expression. The OR even had the effect of increasing plasma triacylglycerides (TAG) and cholesterol in the very low density lipoprotein (VLDL-C) fraction. Neither total bile acids nor total primary or secondary bile acids were significantly affected by feeding rats the OBP or its fractions. Principal component analysis combining all markers revealed that the controls could be completely separated from OBP, OE, and OR groups in the scores plot and also that OE and OR groups were separated. Plasma lipids and bile acid excretion were the discriminating loading factors for separating OE and OR but also contributed to the separation of onion-fed animals and controls. It was concluded that the onion byproduct did not present significant beneficial effects on individual markers related to plasma lipid transport in this healthy rat model but that onion byproduct contains factors with the ability to modulate plasma lipids and lipoprotein levels.

Programmed aortic dysfunction and reduced Na+,K+-ATPase activity present in first generation offspring of lard-fed rats does not persist to the second generation.

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.

Developmental programming of aortic and renal structure in offspring of rats fed fat-rich diets in pregnancy.

Evidence from human and animal studies suggests that maternal nutrition can induce developmental programming of adult hypertension in offspring. We have previously described a model of maternal dietary imbalance in Sprague-Dawley rats whereby administration of a maternal diet rich in animal lard programmes the development of increased blood pressure, insulin resistance, dyslipidaemia, obesity and mesenteric artery endothelial dysfunction in adult offspring. To further characterize the mechanism of hypertension in this model we have examined vascular and renal structure in adult offspring of Sprague-Dawley rats fed a control diet (OC) or lard-rich diet (OHF) during pregnancy and suckling followed by a control diet post-weaning. To gain further insight, we assessed aortic reactivity and elasticity in an organ bath preparation and renal renin and Na+,K+-ATPase activity. Plasma aldosterone concentration was also measured. Stereological examination of the aorta in OHF demonstrated reduced endothelial cell volume and smooth muscle cell number compared with OC. Adult OHF animals showed increased aortic stiffness and reduced endothelium-dependent relaxation. Renal stereology showed no differences in kidney weight, glomerular number or volume in OHF compared with OC, but renin and Na+,K+-ATPase activity were significantly reduced in OHF compared with controls. Programmed alterations to aortic structure and function are consistent with previous observations that exposure to maternal high fat diets produces systemic vascular changes in the offspring. Despite normal renal stereology, altered renal Na+,K+-ATPase and renin activity offers further insight into the mechanism underlying the increased blood pressure characteristic of this model.