To save content items to your account,
please confirm that you agree to abide by our usage policies.
If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account.
Find out more about saving content to .
To save content items to your Kindle, first ensure firstname.lastname@example.org
is added to your Approved Personal Document E-mail List under your Personal Document Settings
on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part
of your Kindle email address below.
Find out more about saving to your Kindle.
Note you can select to save to either the @free.kindle.com or @kindle.com variations.
‘@free.kindle.com’ emails are free but can only be saved to your device when it is connected to wi-fi.
‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.
The incidence of obesity and its metabolic complications are rapidly increasing and become a major public health issue. This trend is associated with an increase in the prevalence of non-alcoholic fatty liver disease (NAFLD), insulin resistance and diabetes. The sequence of events leading to NAFLD progression and mitochondrial dysfunction and their interrelation remains to be elucidated. This study aimed to explore the installation and progression of NAFLD and its association with the liver mitochondrial structure and activity changes in rats fed an obesogenic diet up to 20 weeks. Male Wistar rats were fed either a standard or high-fat–high-fructose (HFHFR) diet and killed on 4, 8, 12, 16 and 20 weeks of diet intake. Rats fed the HFHFR diet developed mildly overweight, associated with increased adipose tissue weight, hepatic steatosis, hyperglycaemia and hyperinsulinaemia after 8 weeks of HFHFR diet. Hepatic steatosis and many biochemical modifications plateaued at 8–12 weeks of HFHFR diet with slight amelioration afterwards. Interestingly, several biochemical and physiological parameters of mitochondrial function, as well as its phospholipid composition, in particular cardiolipin content, were tightly related to hepatic steatosis installation. These results showed once again the interrelation between hepatic steatosis development and mitochondrial activity alterations without being able to say whether the mitochondrial alterations preceded or followed the installation/progression of hepatic steatosis. Because both hepatic steatosis and mitochondrial alterations occurred as early as 4 weeks of diet, future studies should consider these four 1st weeks to reveal the exact interconnection between these major consequences of obesogenic diet intake.
The prevalence of the metabolic syndrome components including abdominal obesity, dyslipidaemia and insulin resistance is increasing in both developed and developing countries. It is generally accepted that the development of these features is preceded by, or accompanied with, impaired mitochondrial function. The present study was designed to analyse the effects of a mitochondrial-targeted lipophilic ubiquinone (MitoQ) on muscle lipid profile modulation and mitochondrial function in obesogenic diet-fed rats. For this purpose, twenty-four young male Sprague–Dawley rats were divided into three groups and fed one of the following diets: (1) control, (2) high fat (HF) and (3) HF+MitoQ. After 8 weeks, mitochondrial function markers and lipid metabolism/profile modifications in skeletal muscle were measured. The HF diet was effective at inducing the major features of the metabolic syndrome – namely, obesity, hepatic enlargement and glucose intolerance. MitoQ intake prevented the increase in rat body weight, attenuated the increase in adipose tissue and liver weights and partially reversed glucose intolerance. At the muscle level, the HF diet induced moderate TAG accumulation associated with important modifications in the muscle phospholipid classes and in the fatty acid composition of total muscle lipid. These lipid modifications were accompanied with decrease in mitochondrial respiration. MitoQ intake corrected the lipid alterations and restored mitochondrial respiration. These results indicate that MitoQ protected obesogenic diet-fed rats from some features of the metabolic syndrome through its effects on muscle lipid metabolism and mitochondrial activity. These findings suggest that MitoQ is a promising candidate for future human trials in the metabolic syndrome prevention.
The incidence of metabolic syndrome components including obesity, lipid deregulation, insulin resistance (IR) and non-alcoholic fatty liver disease is increasing rapidly in wealthy societies. The present study was designed to determine the effect of different nutritional lipid patterns (quantity and quality) on lipid utilisation and oxidative stress in the liver and muscle of rats in an integrated fashion. A total of forty-eight Wistar male rats were fed for 12 weeks with a mixed, lard or fish-oil diet, containing either 50 or 300 g lipid/kg. Rats developed liver steatosis associated with moderate liver injury when fed the 30 % lipid diets, in spite of the absence of overt obesity or IR, except when fed the lard 30 % lipid diet. The intake of the 30 % lipid diets decreased hepatic lipogenesis and mitochondriogenesis and increased lipid peroxidation and protein oxidation. Surprisingly, muscle lipid content was not modified whatever the administered diet. The intake of the 30 % lipid diets increased the muscle protein expression of fatty acid (FA) translocase/cluster of differentiation 36 (FAT/CD36), PPARγ co-activator 1α (PGC-1α) and muscle carnitine palmitoyltransferase 1 (m-CPT1), reflecting increased FA transport in the muscle associated with increased oxidative metabolism. The lard 30 % lipid diet led to IR without modifying the muscle lipid content. The fish-oil 30 % lipid diet failed to prevent the development of hepatic steatosis and made the tissues more prone to oxidation. Overall, the present study suggests that the FA composition of muscle is more important than lipid accumulation itself in the modulation of insulin sensitivity, and indicates that precaution should be taken when advising an unphysiologically high (pharmacological) supplementation with long-chain n-3 PUFA.
Dietary lipids are known to affect the composition of the biological membrane and functions that are involved in cell death and survival. The mitochondrial respiratory chain enzymes are membrane protein complexes whose function depends on the composition and fluidity of the mitochondrial membrane lipid. The present study aimed at investigating the impact of different nutritional patterns of dietary lipids on liver mitochondrial functions. A total of forty-eight Wistar male rats were divided into six groups and fed for 12 weeks with a basal diet, lard diet or fish oil diet, containing either 50 or 300 g lipid/kg. The 30 % lipid intake increased liver NEFA, TAG and cholesterol levels, increased mitochondrial NEFA and TAG, and decreased phospholipid (PL) levels. SFA, PUFA and unsaturation index (UI) increased, whereas MUFA and trans-fatty acids (FA) decreased in the mitochondrial membrane PL in 30 % fat diet-fed rats compared with 5 % lipid diet-fed rats. PL UI increased with fish oil diet v. basal and lard-rich diets, and PL trans-FA increased with lard diet v. basal and fish oil diets. The 30 % lipid diet intake increased mitochondrial membrane potential, membrane fluidity, mitochondrial respiration and complex V activity, and decreased complex III and IV activities. With regard to lipid quality effects, β-oxidation decreased with the intake of basal or fish oil diets compared with that of the lard diet. The intake of a fish oil diet decreased complex III and IV activities compared with both the basal and lard diets. In conclusion, the characteristics and mitochondrial functions of the rat liver mitochondrial membrane are more profoundly altered by the quantity of dietary lipid than by its quality, which may have profound impacts on the pathogenesis and development of non-alcoholic fatty liver disease.
Accumulation of muscle TAG content and modification of muscle phospholipid fatty acid pattern may have an impact on lipid metabolism, increasing the risk of developing diabetes. Some polyphenols have been reported to modulate lipid metabolism, in particular those issued from red grapes. The present study was designed to determine whether a grape polyphenol extract (PPE) modulates skeletal muscle TAG content and phospholipid fatty acid composition in high-fat–high-sucrose (HFHS) diet-fed rats. Muscle plasmalemmal and mitochondrial fatty acid transporters, GLUT4 and lipid metabolism pathways were also explored. The PPE decreased muscle TAG content in HFHS/PPE diet-fed rats compared with HFHS diet-fed rats and induced higher proportions of n-3 PUFA in phospholipids. The PPE significantly up-regulated GLUT4 mRNA expression. Gene and protein expression of muscle fatty acid transporter cluster of differentiation 36 (CD36) was increased in HFHS diet-fed rats but returned to control values in HFHS/PPE diet-fed rats. Carnitine palmitoyltransferase 1 protein expression was decreased with the PPE. Mitochondrial β-hydroxyacyl CoA dehydrogenase was increased in HFHS diet-fed rats and returned to control values with PPE supplementation. Lipogenesis, mitochondrial biogenesis and mitochondrial activity were not affected by the PPE. In conclusion, the PPE modulated membrane phospholipid fatty acid composition and decreased muscle TAG content in HFHS diet-fed rats. The PPE lowered CD36 gene and protein expression, probably decreasing fatty acid transport and lipid accumulation within skeletal muscle, and increased muscle GLUT4 expression. These effects of the PPE are in favour of a better insulin sensibility.
Older people are vulnerable to zinc deficiency, which may impact upon their mood. This randomised, placebo-controlled, double-blind intervention study aimed to investigate the effect of oral zinc gluconate supplementation (15 mg/d; 30 mg/d; and placebo) on subjective mood (affect) in older Europeans.
Healthy volunteers (n 387) aged 55–87 years were recruited.
Volunteers in Rome (Italy; n 108) and Grenoble (France; n 91) were aged 70–87 years and those in Coleraine (Northern Ireland; n 93) and Clermont-Ferrand (France; n 95) were aged 55–70 years.
Mood was measured using the Positive and Negative Affect Scale on four occasions per day over 4 d at baseline, 3 and 6 months post-intervention.
Mixed ANOVA indicated that neither positive nor negative affect altered in response to zinc (15 mg/d or 30 mg/d) compared to placebo in either the 55–70 years or the ≥70 years age group.
These results suggest that zinc does not benefit mood in healthy older people.
High-fat or high-fat–high-sucrose diets are known to induce non-alcoholic fatty liver disease and this is emerging as one of the most common liver diseases worldwide. Some polyphenols have been reported to decrease rat hepatic lipid accumulation, in particular those extracted from red grapes such as resveratrol. The present study was designed to determine whether a polyphenol extract (PPE), from red grapes, modulates liver fatty acid composition and desaturase activity indexes in rats fed a high-fat–high-sucrose (HFHS) diet, and to explore whether sirtuin-1 deacetylase activation was implicated in the effect of the PPE against liver steatosis. The effect of this PPE on mitochondriogenesis and mitochondrial activity was also explored. The PPE decreased liver TAG content in HFHS+PPE diet-fed rats in comparison with HFHS diet-fed rats. The PPE had no effect on liver fatty acid composition, desaturase activity indexes and stearoyl-CoA desaturase 1 (SCD1) gene expression. Sirtuin-1 deacetylase protein expression was significantly increased with the PPE; AMP kinase protein expression was higher with the PPE in comparison with the HFHS rats, but no modification of phosphorylated AMP kinase was observed. Protein expression of phospho-acetyl-CoA carboxylase was decreased in HFHS rats and returned to basal values with the PPE. Finally, the PPE modulated PPARγ coactivator-1α (PGC-1α) but did not modify mitochondriogenesis and mitochondrial activity. In conclusion, the PPE partially prevented the accumulation of TAG in the liver by regulating acetyl-CoA carboxylase phosphorylation, a key enzyme in lipid metabolism, probably via sirtuin-1 deacetylase activation. However, the PPE had no effect on the qualitative composition of liver fatty acids.
Taste acuity declines with age and may be dependent upon Zn status. The aim of the present double-blind, randomised controlled intervention trial has been to determine taste acuity in response to Zn supplementation (placebo, or 15 or 30 mg Zn/d). Healthy older European adults aged 70–87 years were recruited within Italy (Rome) (n 108) and France (Grenoble) (n 91) to the European Commission-funded Zenith project. A signal detection theory approach was adopted for taste assessment. The data were converted to R indices and analysed by repeated-measures ANOVA controlling for baseline taste acuity as well as serum and erythrocyte Zn. Serum Zn increased post-intervention, indicating compliance with the intervention. Results differed across geographical region. Salt taste acuity was greater in response to Zn (30 mg) than placebo post-intervention among those recruited in Grenoble. There was no apparent change in acuity for sweet, sour or bitter taste in response to Zn. Supplemented Zn may have potential to enhance salt taste acuity in those over the age of 70 years. Further research is required to determine if enhanced salt taste acuity is reflected in the eating experiences of older individuals.
Given the key role of Zn in many physiological functions, optimal Zn status could be a predictive parameter of successful ageing. However, the benefit of Zn supplementation is still a matter of debate since Zn supplementation has been reported to be associated with the alteration of Cu status and lipid metabolism. As part of the Zenith Project, the present study aimed to investigate, in free-living healthy European middle-aged and older subjects, the effect of Zn supplementation on the biochemical status of Zn, Fe and Cu and on lipid profile. Volunteers aged 55–70 (n 188) and 70–85 (n 199) years old participated in a double-blinded, randomised study and received a daily placebo, or Zn as 15 or 30 mg for 6 months. Zn supplementation did not significantly modify erythrocyte Zn levels or erythrocyte Cu,Zn-superoxide dismutase activity. But Zn supplementation at 15 or 30 mg/d for 6 months increased significantly serum Zn levels and Zn urinary excretion with no major adverse effects on Fe and Cu status or on lipid metabolism. However, Zn supplementation at 30 mg/d showed some age- and sex-dependent alterations in Fe status or lipid profile. Therefore, with respect to the key role of an optimal Zn status in successful ageing, Zn supplementation at 15 mg/d, when necessary, could be safely proposed regarding lipids and the risk of interaction with Fe and Cu.
A randomised double-blind placebo-controlled design was employed to investigate the effects of Zn supplementation on cognitive function in 387 healthy adults aged 55–87 years. Several measures of visual memory, working memory, attention and reaction time were obtained using the Cambridge Automated Neuropsychological Test Battery at baseline and then after 3 and 6 months of 0 (placebo), 15 or 30 mg Zn/d. Younger adults (<70 years) performed significantly better on all tests than older adults (>70 years), and performance improved with practice on some measures. For two out of eight dependent variables, there were significant interactions indicating a beneficial effect (at 3 months only) of both 15 and 30 mg/d on one measure of spatial working memory and a detrimental effect of 15 mg/d on one measure of attention. Further work is required to establish whether these findings generalise to older adults in poorer mental and physical health and with less adequate Zn intake and status than the present sample.
Zn has been shown to possess antioxidant properties in vitro and in vitro. As inadequate dietary Zn intake has been reported in these populations, Zn supplementation may protect against oxidative stress and thereby limit the progression of degenerative diseases in such populations. We conducted the present study to evaluate the long-term supplementation effects of two moderate doses of Zn on in vitro Cu-induced LDL oxidation in French men and women.Three groups of sixteen healthy subjects aged 55–70 years from each sex participated in this randomized double-blind, placebo-controlled study. Each group received for six months either 0, 15 or 30mg supplemental Zn per d. At the beginning and at the end of the supplementation periods, dietary intakes of Zn, Cu, Fe and vitamin E were estimated using 4d food-intake records (including the weekend) and the GENI program. Zn, Cu, Fe and vitamin E statuswere also determined. In vitro LDL oxidizability (basal conjugated diene level, maximal conjugated diene formation and lag time) and lipid parameters were also determined. Dietary intakes of Zn, Cu, Fe and vitamin E were adequate in this population. Zn supplementation significantly increased serum Zn levels but did not significantly modify Cu, Fe or vitamin E status. However, Zn supplementation had no effect on in vitro LDL oxidation parameters, nor were there any sex-related differences in in vitro LDL oxidizability. The present study showed that long-term Zn supplementation of healthy subjects aged 55–70 years had no effect on in vitro Cu-induced LDL oxidation under the study conditions.
It is believed that rare earth elements are not absorbed, and thus they are generally used in some mineral absorption studies as a faecal marker. The aim of the present study was to determine the effect of inulin intake and age on dysprosium (Dy) absorption in rats. Eighty male Wistar rats of four different ages (2, 5, 10 and 20 months) were randomised into either a control group or a group receiving 3·75% inulin in their diet for 4d and then 7·5% inulin until the end of the study. The animals were fed fresh food and water ad libitum for 30d. The intestinal absorption of Dy was determined from a 4d (day 21 to day 25) balance study. Mean faecal Dy recovery (%) in the eight groups (3 months control, 3 months inulin, 6 months control, 6 months inulin, 11 months control, 11 months inulin, 21 months control, 21 months inulin) was 94·0 (sd 8·6), 64·8 (sd 10·1), 95·8 (sd 9·4), 81·5 (sd 12·1), 98·4 (sd 9·8), 87·8 (sd 9·5), 97·8 (sd 6·2) and 84·9 (sd 10·9), respectively. Our results showed clearly that dietary inulin intake decreased faecal Dy recovery in all four rat groups, and faecal Dy recovery was significantly higher in the old rats (10 and 20 months) than in the young and adult rats. These results show that the faecal recovery (or intestinal absorption) of Dy may vary greatly with nutritional or physiological states such as inulin intake or age. The use of rare earth elements as a faecal marker should be thus validated under each nutritional or physiological state before being employed in mineral absorption studies.
Lead is a ubiquitous heavy metal and its toxicity remains an important public health issue. In previous work, we reported that ingestion of rhamnogalacturonan-II dimer (dRGII), a pectic polysaccharide, may decrease intestinal absorption and status of Pb in rats. Here, we evaluated the potential detoxifying effect of different doses of dRGII after chronic oral Pb exposure in rats. For this purpose, six groups of ten male Wistar rats weighing 150 g were treated as follows: group A received a semi-purified control diet for 6 weeks; groups B, C, D, E and F received the same diet plus 3 mg Pb (as acetate) for 3 weeks. Group B was then killed. Groups C, D, E, and F continued to receive the semi-purified control diet containing 0, 2, 6 or 18 g dRGII/kg diet for 3 additional weeks. During the last 5 d, a Pb conventional balance study was performed. Rats were then anaesthetized and tissues were sampled for Pb and essential minerals assay. The results showed that residual Pb in the added dRGII was not available for absorption. However, the added dRGII failed to induce any significant increase in faecal or urinary Pb excretion. Consequently, at the end of the study the intestinal Pb absorption and balance remained unchanged in the animals receiving the different doses of dRGII. In line with this, we showed that dRGII administration was not effective in decreasing tibia or kidney Pb levels in rats. In conclusion, Pb complexed by dRGII in fruits and vegetables and fruit juice is thus mostly unavailable for intestinal absorption. However, the addition of dRGII after chronic Pb exposure does not help Pb detoxification.
Resistant starch and inulin are complex carbohydrates that are fermented by the microflora and known to increase colonic absorption of minerals in animals. The fermentation of these substrates in the large bowel to short-chain fatty acids is the main reason for this increase in mineral absorption. The purpose of the present study was to examine the potential synergistic effect of a combination of these two fermentable carbohydrates. For this purpose, thirty-two adult male Wistar rats weighing 200 g were used in the present study. The rats were distributed into four groups, and fed for 21 d a fibre-free basal purified diet or diet containing 100 g inulin, or 150 g resistant starch (raw potato starch)/kg diet or a blend of 50 g inulin and 75 g resistant starch/kg diet. After an adaptation period of 14 d, the rats were then transferred to metabolic cages and dietary intake, faeces and urine were monitored for 5 d. The animals were then anaesthetized and caecal Ca and Mg absorption were measured. Finally, the rats were killed and blood, caecum and tissues were sampled. Ca and Mg levels were assessed in diets, faeces, urine, caecum and plasma by atomic absorption spectrometry. Our results confirmed that inulin and resistant starch ingestion led to considerable caecal fermentation in the three experimental groups compared with the control group diet. Moreover, both carbohydrates significantly increased the intestinal absorption and balance of Ca and Mg, without altering the plasma level of these two minerals. Interestingly, the combination of the studied carbohydrates increased significantly (P<0·05) the caecal soluble Ca and Mg concentrations, the apparent intestinal absorption and balance of Ca, and non-significantly the plasma Mg level. In conclusion, a combination of different carbohydrates showed synergistic effects on intestinal Ca absorption and balance in rats. Further studies with other types of carbohydrate combinations should be carried out to extend these findings.
Consumption of unrefined whole flour is thought to affect mineral bioavailability because it contains high levels of fibre and phytic acid. The present experiment was designed to study the absorption of minerals from diets based on wholewheat flour and white wheat flour in rats. Two groups of male Wistar rats were fed on the diets for 3 weeks and absorption and tissue retention of minerals were studied. The rats fed on the wholewheat flour diet had significantly greater food intake, weight gain, faecal excretion and intestinal fermentation than those fed on the white flour diet. Mineral intakes, except for Ca, were significantly greater in rats fed on the wholewheat flour diet (4-fold for Mg, 2-fold for Fe and Zn). A significant rise in the apparent absorption of Fe (%) and a significant decrease in the apparent absorption of Zn (%) were observed. The amounts of minerals absorbed (mg/d) were significantly enhanced (excepted for Ca) with the wholewheat flour diet. Moreover, plasma and tibia levels of Mg and plasma, liver and tibia levels of Fe were significantly increased in rats fed on the wholewheat flour diet compared with those fed on the white flour diet. In conclusion, wholewheat flour, rich in phytic acid and minerals, did not have a negative effect on mineral absorption, but rather improved the bioavailability of some minerals. Human studies are needed to confirm these rat results before extrapolation to human nutrition.
The amount of dietary trace elements absorbed from a meal depends, among other factors, on the quantities of certain minor plant constituents present in the meal. These substances can act as ligands and bind trace elements in the digestive tract in available or unavailable forms for absorption. The present study was designed to investigate the extent to which different polyphenols (PP) may influence Zn and Cu absorption in rats. Different PP of nutritional interest (chlorogenic acid, caffeic acid, catechin and rutin) were studied using meals extrinsically-labelled with stable isotopes67Zn and 65Cu. Male Wistar rats were fed on a non-labelled semi-synthetic diet containing (mg/kg) 38 Fe, 35 Zn and 7·5 Cu for 8 d. PP were dissolved in dimethyl sulfoxide as the solvent and added to the meal at 1 g/kg during 3 d before isotope administration and until the end of the experiment (a further 3 d). The control group received the dimethyl sulfoxide only. After overnight food deprivation, rats were fed on the labelled test meals (4 g diet+0·1 mg 67Zn and 0·1 mg 65Cu) with 0·5 mg Dy as a faecal marker. Faeces and urine pools were collected for 3 d and analysed for 67Zn and65 Cu isotopic enrichment using the inductively-coupled plasma mass spectrometry technique. Zn absorption was significantly less in rats fed on chlorogenic acid or caffeic acid than in the control group. Catechin ingestion non-significantly inhibited 67Zn absorption. However, the PP studied were without effect on Cu absorption. The study illustrates the effect of metal-binding phenolic compounds on mineral nutrition in the rat, and the possible importance of the effects of different foods rich in these compounds on mineral absorption in man.
The present work aimed to investigate the feasibility of using stable isotopes and inductively-coupled plasma mass spectrometry (ICP/MS) to study Mg absorption in rats. Male Wistar rats, aged 7 weeks and weighing 180g, were used. They were fed on a semi-purified diet containing 1070mg Mg/kg, and had free access to feed and distilled water. In the first experiment, after a 16d adaptation period, two doses of enriched 25Mg (6 and 12mg) were administered by oral intubation, faeces and urine were collected daily and blood was sampled. Isotope ratios were determined by ICP/;MS. ‘True’ absorption values, using the faecal isotope data, were 0.63 and 0.56 in rats receiving 6 and 12mg 25Mg respectively, while apparent absorption was 0.50 for two successive periods of metabolic balance studies. Moreover, the oral isotope administration resulted in a measurable isotopic enrichment in plasma within hours which was still detectable on the third day following the isotope administration. In the second experiment, investigating the double labelling technique, similar rats were dosed Simultaneously with 5mg 26Mg orally (premixed with diet) and 0.29mg 25Mg intravenously. The calculated Mg true absorption values were very similar when calculated from blood or urine data (0.38) but were lower than that obtained from faecal data (0.50). The possible causes of such an unexpected difference and limits of the double labelling technique for Mg absorption are discussed here. Together these results indicate that although 25Mg and 26Mg isotopes have high natural abundance, the described methodology permits meaningful investigations of Mg bioavailability and metabolism
Email your librarian or administrator to recommend adding this to your organisation's collection.