Dietary habits are often considered as a pathogenic factor for fatty liver. The impact of dietary intake and steatosis on drug metabolism remains poorly investigated. Our aim was to assess the effect of dietary intake on in vivo cytochrome P450 (CYP) activities in eleven patients with abnormal liver function tests potentially due to fatty liver and associated with a high-sugar diet. Liver function tests, liver volume, aminopyrine breath test (ABT) and chlorzoxazone (CZ) pharmacokinetics (area under the curve, AUC) which are known to reflect CYP2E1 activity were evaluated before and after 2 months restriction of dietary sugar intake. Features at inclusion were an increased BMI (30·3 (sd 3·2) kg/m2), high hepatic volume (1·96 (sd 0·48) litres), hyperechogenic liver parenchyma, elevated liver enzyme activities (alanine aminotransferase (EC 2.6.1.2) 58·6 (sd 17·4) IU/l with alanine aminotransferase : aspartate aminotransferase (EC 2.6.1.1) ratio > 1), together with a normal ABT value (0·68 (sd 0·21) % specific activity of administered dose of [14C]aminopyrine in breath after 1 h) and a high CYP2E1 activity (CZ AUC 20·3 (sd 7·1) μg/ml per h). A dietary sugar restriction was prescribed. On the basis of repeated interviews by the same dietitian, unaware of any clinical and biochemical data, six patients remained compliant to the diet and exhibited reductions in BMI (P < 0·001), serum alanine aminotransferase (P = 0·008), liver volume (P = 0·002) and CYP2E1 activity (P = 0·007), a significant increase in ABT (P < 0·001) together with the disappearance of liver hyperechogenicity at ultrasound. In contrast, the five non-compliant patients did not show any significant change in any of these variables. In conclusion, CYP2E1 activity is induced in patients with perturbations of liver function tests potentially due to fatty liver. In these patients, effective dietary sugar restriction is associated with a reduction in liver volume, a reduction in CYP2E1 activity and an increased aminopyrine metabolism rate.

The fatty acid compositions of white adipose tissue, colostrum and mature milk triacylglycerols from Mauritian (n 13) and French (n 15) women were analysed and compared in order to highlight cultural differences in dietary intakes and their influence on milk fatty acid composition. Erythrocyte phosphatidylethanolamine and phosphatidylcholine fatty acid compositions were also investigated in their term infants, breast-fed over a period of 6 weeks. Fatty acid composition (g/100 g) of all samples was determined by GLC and anthropometric measurements were assessed in the two populations at birth and on day 42. Comparisons of white adipose tissue fatty acid compositions demonstrated lower levels of saturated (23·64 (se 1·54) v. 29·75 (se 0·67), P < 0·01) and monounsaturated (39·44 (se 1·27) v. 54·84 (se 0·75), P < 0·001) fatty acids and higher levels of polyunsaturated fatty acids (n−6 series: 32·47 (se 1·31) v. 14·32 (se 0·47), P < 0·001 and n−3 series: 2·87 (se 0·49) v. 0·80 (se 0·07), P < 0·01) in Mauritian than in French samples respectively. Accordingly, milk fat of the Mauritian women contained higher levels of parent essential fatty acids and their longer-chain derivatives than did milk fat from French women. Higher levels of parent essential fatty acids but lower levels of long-chain polyunsaturated fatty acids were found in erythrocyte phospholipids of Mauritian infants compared with French infants. Infants' erythrocyte arachidonate and docosahexaenoate contents did not correlate with any anthropometric variables at birth or at day 42, neither did they correlate with anthropometric variation over the study period. Our results suggest the lack of a simple relationship between the amount of long-chain polyunsaturated fatty acids in human milk and their accretion in the erythrocyte phospholipids of breast-fed infants when provided concomitantly with high levels of both linoleic and α-linolenic acids in ratios which fall within recommended ranges.

In a 9-week study seventy-six healthy adult volunteers with an average age of 44 (sd 11) years, with baseline plasma total cholesterol levels below 8 mmol/l, received in a balanced, double-blind, crossover design, a total of three different table spreads for personal use. Two spreads were fortified either with free (non-esterified) vegetable-oil sterols, mainly from soyabean oil (31 g sterol equivalents/kg; 0·8 g/d) or sheanut-oil sterols (133 g sterol equivalents/kg; 3·3 g/d). One spread was not fortified (control). Average intake of spread was 25 g/d for 3 weeks. None of the spreads induced changes in blood clinical chemistry or haematology. Plasma total- and LDL-cholesterol concentrations were statistically significantly reduced by 3·8% and 6% (both 0·19 mmol/l) respectively, for the spread enriched with free soyabean-oil sterols compared with the control spread. The spread enriched with sheanut-oil sterols did not lower plasma total- and LDL-cholesterol levels. None of the plant-sterol-enriched spreads affected plasma HDL-cholesterol concentrations. Plasma-lipid-standardized concentrations of α- plus β-carotene were not statistically significantly affected by the soyabean-oil sterol spread in contrast to lipid-standardized plasma lycopene levels which showed a statistically significant decrease (9·5%). These findings indicate that a daily intake of free soyabean-oil sterols as low as 0·8 g added to a spread is effective in lowering blood total- and LDL-cholesterol levels with limited effects on blood carotenoid levels. The lowering in total- and LDL-cholesterol blood levels due to consumption of the vegetable-oil-sterol-enriched spread may be helpful in reducing the risk of CHD for the population.

The influence of Cu supplementation of the usual diet for 6 weeks on biochemical markers of bone turnover and on putative indices of Cu status was investigated in healthy adults (twelve male and twelve female) aged 22–46 years, who participated in a double-blind placebo-controlled repeated crossover study. The study consisted of three 6-week supplementation regimens of 3 mg CuSO4, 3 mg Cu–glycine chelate (CuGC), and 6 mg CuGC, each separated by placebo periods of equal length. During baseline and on the last day of each dietary period, fasting morning first-void urine and fasting blood serum, plasma and erythrocytes were collected. The habitual dietary Cu intakes in males and females were approximately 1·4 and 1·1 mg/d respectively. Females had significantly higher (50 %) plasma caeruloplasmin (Cp) protein concentrations than males at baseline. Cu supplementation had no effect on erythrocyte superoxide dismutase (SOD, EC 1.15.1.1) activity or plasma Cp protein (putative indices of Cu status) in the total group. Similarly, serum osteocalcin (a marker of bone formation), urinary creatinine (Cr) concentration, urinary pyridinoline : Cr or deoxypyridinoline : Cr excretion (markers of bone resorption) were unaffected in either the total group or in males and females separately, by any Cu supplementation regimen. It is concluded that Cu supplementation of the usual diet in healthy adult males and females had no effect on biochemical markers of bone formation or bone resorption over 6-week periods.

The purpose of the present study was to investigate the effects of Se restriction on the excretion of Se in men who had consumed high levels of this element during their entire lives. With the use of stable isotopes of Se as selenite, the excretion of methylated Se in urine was investigated in Chinese men (n 10) who had habitual chronic high intakes of this element. The relationship between either urine Se or trimethylselenonium (TMSe) to the estimated long-term Se intake was not linear over the entire range of intake, which was also true for the infusion of labelled selenite. A non-linear relationship was also found between urine TMSe and urine Se both for TMSe arising from catabolism of endogenous body Se and that from infused selenite. The data suggest a close precursor–product relationship of urine Se and its TMSe component based on the nearly identical specific activities for these two selenocompounds. Although dimethylselenide in breath was not measured in the present study, combining urinary TMSe with this breath test may be more useful in the assessment of long-term Se status.

The oxidative capacity of the liver, the heart and skeletal muscles for fatty acids were investigated in preruminant calves fed for 19 d on a milk-replacer containing either coconut oil (CO, rich in 12:0) or tallow (rich in 16:0 and 18:1). Weights of the total body and tissues did not differ significantly between the two groups of animals but plasma glucose and insulin concentrations were lower in the CO group. Feeding on the CO diet induced an 18-fold increase in the hepatic concentration of triacylglycerols. Rates of total and peroxisomal oxidation of [1-14C]laurate, [1-14C]palmitate and [1-14C]oleate were measured in fresh tissue homogenates. Higher rates of total oxidation in liver homogenate and of peroxisomal oxidation in liver, heart and rectus abdominis muscle homogenates were observed with laurate used as substrate. Furthermore, the relative contribution of peroxisomes to total oxidation was 1·9-fold higher in the liver and in the heart with laurate than with oleate or palmitate. Finally, the peroxisomal oxidation rate of oleate was 1·5-fold higher in the hearts of calves fed on the CO diet. Whatever the tissue, citrate synthase (CS, EC 4.1.3.7) and cytochrome c oxidase (COX, EC 1.9.3.1) activities were similar between the two groups of calves but the COX : CS activity ratio was lower in the liver of the CO group. In conclusion, laurate is better catabolized by peroxisomes than long-chain fatty acids, especially in the liver. Elongation of lauric acid after partial oxidation might explain the hepatic triacylglycerol accumulation in calves fed on the CO diet.

Effects of the conjugated linoleic acid (CLA) isomers cis-9, trans-11 (c9, t11 CLA) and trans-10, cis-12 (t10, c12 CLA) on lipid metabolism and markers of peroxisome proliferation were investigated in hamsters fed on purified diets containing 30 % energy as fat and 0·1 g cholesterol/kg for 8 weeks. Four groups (n 32 each) received diets without CLA (control), with a mixture of equal amounts of c9, t11 and t10, c12 CLA (CLA mix), with c9, t11 CLA, and with t10, c12 CLA. The total amount of CLA isomers was 1·5 % energy or 6·6 g/kg diet. CLA was incorporated into glycerides and exchanged for linoleic acid in the diet. Compared with the control, the CLA mix and t10, c12 CLA decreased fasting values of LDL- (21 and 18 % respectively) and HDL-cholesterol (8 and 11 %), increased VLDL-triacylglycerol (80 and 61 %), and decreased epididymal fat pad weights (9 and 16 %), whereas c9, t11 CLA had no significant effects. All CLA preparations increased liver weight, but not liver lipids. However, the increase in liver weight was much less in the c9, t11 CLA group (8 %) than in the other two groups (25 %) and might have been caused by the small amount of t10, c12 CLA present in the c9, t11 CLA preparation. Liver histology revealed that increased weight was due to hypertrophy. Markers of peroxisome proliferation, such as cyanide-insensitive palmitoyl CoA oxidase (EC 1.3.3.6) and carnitine acetyl transferase (EC 2.3.1.7) activities, were not increased by CLA. Both c9, t11 CLA and t10, c12 CLA were incorporated into phospholipids and triacylglycerols, but t10, c12 CLA only about half as much as c9, t11 CLA. In addition, linoleic acid and linolenic acid concentrations were lower in lipids of the t10, c12 CLA group compared with the c9, t11 CLA group. These data suggest that t10, c12 CLA stimulated the oxidation of all C18 polyunsaturated fatty acids. The results indicate that the t10, c12 CLA isomer, and not the so-called natural CLA isomer (c9, t11), is the active isomer affecting lipid levels in hamsters.

The aim of the present work was to assess the influence of dietary lipid source on fatty acid phospholipid profiles and on lipid mobilization. Forty male Wistar rats were divided into four groups and fed on high-fat diets which provided olive oil, sunflower oil, palm oil or beef tallow. All rats received the same amount of energy to avoid hyperphagia and differences in energy intake among groups. Phospholipid fatty acids were determined by GC. Lipolysis was stimulated in subcutaneous and perirenal isolated adipocytes by several lipolytic agents, and assessed by the determination of released glycerol. After 4 weeks of feeding, differences in body and adipose tissue weights were not observed. Dietary regimens caused great changes in adipose tissue phospholipid composition: rats fed on palm oil and beef tallow had higher concentrations of saturated fatty acids and animals fed on olive oil or sunflower oil had greater amounts of oleic and linoleic acids, respectively. These modifications did not lead to important changes in adipocyte lipolysis. Significant differences were only observed between palm-oil- and beef-tallow-fed groups when lipolysis was stimulated by isoproterenol in subcutaneous adipocytes. The fact that our feeding protocol did not induce differences in fat accumulation among groups avoids misinterpretations due to adiposity changes. The differences observed between both saturated-fat-fed groups, therefore, should only be attributable to dietary lipids. Despite this effect, the data from this work indicate that some diet-induced changes in adipose tissue fatty acid composition may have little effect on overall function.