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Un niveau élevé d'acides gras saturés (AGS) dans le sang a un effet délétère sur les muscles squelettiques en inhibant à la fois la régénération des fibres musculaires et la synthèse des protéines musculaires. Du fait de sa richesse en AGS, l’huile de palme est controversée. Cette étude avait pour objectif d’étudier l’effet d’un régime riche en huile de palme (brute et raffinée) sur l’expression des facteurs myogéniques dans le muscle de rats sédentaires et le comparer avec un régime riche en huile d’olive et en Lard. Quarante rats mâles Wistar ont été répartis en 5 groupes de 8 rats chacun : 1 groupe témoin et 4 groupes nourris par des régimes riches en graisse (HFD) contenant respectivement de l’huile de palme brute, de l’huile de palme raffinée, de l’huile d’olive et du lard. Après 12 semaines de régime, les rats ont été sacrifiés et les tissus prélevés L'expression de Pax7, Myf5, MyoD et MyoG a été évaluée par RT-qPCR dans les muscles gastrocnémiens. Aucune différence significative n’a été observée entre régime témoin et HFD concernant les expressions de Pax7, Myf5 et MyoG. L’expression de MyoD s’est avérée significativement plus élevée dans les animaux HFD (p=0,0004) par rapport au témoin ; en particulier dans le régime riche en huile d’olive par rapport aux autres régimes HFD (p=0,05). Aucune altération significative de l’expression des gènes des facteurs de régulation myogénique n’a été observée avec l’huile de palme sous ses 2 formes, brute et raffinée. En conclusion, l’huile de palme, malgré sa richesse en AGS, n’a pas d’effet délétère sur la régénération du muscle squelettique.Mots clés : Régime riche graisses, muscle squelettique, Pax7, Myf5, MyoD, MyoG.

Branched fatty acid esters of hydroxy fatty acids are endogenous lipids reported to have antidiabetic and anti-inflammatory effects. Recently, we showed that 9-palmitic acid esters of hydroxypalmitic acid (9-PAHPA) and 9-oleic acid esters of hydroxypalmitic acid increased insulin sensitivity in mice when incorporated to a chow diet or to a high fat and high sucrose diet. However, preventive supplementation with 9-PAHPA and 9-oleic acid esters of hydroxypalmitic acid in high fat and high sucrose diet mice did not impair significant weight gain or the development of hyperglycemia. The aim of this work was therefore to study whether in two animal models of obesity, namely the classical diet-induced obesity (DIO) and the db/db mice, 9-PAHPA may have beneficial effects against obesity and liver and skeletal muscle metabolic dysfunction. In DIO mice, we observed that 9-PAHPA increased body weight and fat mass. In line with this observation, we found that 9-PAHPA supplementation decreased energy expenditure. In liver and in skeletal muscle, mitochondrial activities and oxidative stress parameters were not modified by 9-PAHPA supplementation. In db/db mice, 9-PAHPA had no effect on the dramatic weight gain and hyperglycemia. In addition, 9-PAHPA supplementation did not correct either the hepatomegaly and hepatic steatosis or the severe muscle atrophy recorded compared with db/+ animals. Likewise, supplementation with 9-PAHPA did not impact the different metabolic parameters analyzed, either in the liver or in the skeletal muscles. However, it decreased insulin resistance in DIO and db/db mice. In conclusion, our study indicated that a long-term intake of 9-PAHPA in DIO and db/db mice improved insulin sensitivity but had only few effects on obesity and associated metabolic disorders.

The use of new lightweight meshes in pelvic organ prolapse (POP) surgery may reduce complications related to mesh retraction (chronic pain, dyspareunia, and mesh exposure). The aim of this study was to investigate changes in the area and position of Uphold Lite™ mesh 6 weeks and 12 months after anterior and/or apical prolapse repair. This observational prospective multicenter study included patients who had undergone transvaginal surgery for symptomatic POP-Q stage ≥ II anterior and/or apical compartment prolapse with placement of Uphold Lite mesh. The dimensions and position of the mesh were evaluated at 6 weeks and 12 months by ultrasonography. Correlations between ultrasonographic mesh characteristics and POP recurrence were analyzed. Fifty evaluable women with an average age of 66.8 years were included. No statistically significant difference in mesh area was found between week 6 and month 12 postoperatively, either at rest (1746.92 vs. 1574.48 mm2; p = 0.15) or on Valsalva (1568.81 vs. 1542.98 mm2; p = 0.65). The ROC-AUC of the distance between the mesh and the bladder neck (M-BN) at 6 weeks for predicting cystocele recurrence at 12 months was 0.764 (95% CI 0.573–0.955) at rest and 0.724 (95% CI 0.533–0.916) on Valsalva. An M-BN distance > 12.5 mm could predict cystocele recurrence at month 12 with a sensitivity of 80% and a specificity of 69%. Ultrasonographic measurements of the Uphold Lite™ mesh appear to remain stable between 6 weeks and 12 months postoperatively. M-BN distance correlates with cystocele recurrence. These results appear to confirm the value of ultrasound in mesh evaluation.

Palm olein (PO) and olive oil (OO) are widely consumed in the world. PO is considered harmful to health, whereas OO is considered healthy. The aim of the study was to compare the effects of consumption of these oils on antioxidant status and inflammation in rats. This was an experimental study in male wistar rats fed a diet containing 30% of each oil. Rats had free access to food and water. After being fed for 12 weeks, animals were sacrificed and liver and aortic blood were collected. Plasma was used for the determination of interleukin-6 (IL-6) and oxidative stress parameters (Superoxide dismutase -SOD; Gluthation peroxidase - GPx; Thiobarbituric acid reactive substances - TBARS; Thiol groups and isoprostane). The inflammation and oxidative stress status as well as the expression of several genes/proteins were also analyzed in liver homogenate. No significant differences were observed between PO and OO in plasma and liver levels of the studied inflammation and oxidative stress parameters. This study showed that the consumption of PO induces an antioxidant status superimposable to that of OO. Key words : Palm olein - Olive oil - Oxidative stress - Inflammation - High fat diet

International audience; Furan fatty acids (FuFAs) are a group of fatty acids containing a furan ring on their aliphatic chain. They are present in small quantities in plants, microorganisms, and animals. The biosynthesis of FuFAs in plants and microorganisms is not fully described and their presence in animals is thought to be exclusively due to food with a high concentration in seafood products, which are themselves consumed by humans. The presence of the furan cycle makes FuFAs highly reactive with reactive oxygen derivatives. The three major biological effects of FuFAs are antioxidant, antimicrobial and anti-inflammatory. More specific studies on health effects have been conducted in recent years: FuFAs and their catabolic degradation products (e.g. CMPF) may influence lipid metabolism, insulin resistance and diabetes, cardiovascular diseases, and neurodegenerative diseases. FuFAs could thus be biomarkers of exposure to a healthy, seafood-rich diet, and also bioactive compounds in our diet capable of modulating signalling pathways with potential beneficial effects against metabolic disorders associated with a Western-style diet.

International audience; P43 is a truncated form of thyroid hormone receptor alpha localized in mitochondria, which stimulates mitochondrial respiratory chain activity. Previously, we showed that deletion of p43 led to reduction of pancreatic islet density and a loss of glucose-stimulated insulin secretion in adult mice. The present study was designed to determine whether p43 was involved in the processes of beta cell development and maturation. We used neonatal, juvenile, and adult p43-/- mice, and we analyzed the development of beta cells in the pancreas. Here, we show that p43 deletion affected only slightly beta cell proliferation during the postnatal period. However, we found a dramatic fall in p43-/- mice of MafA expression (V-Maf Avian Musculoaponeurotic Fibrosarcoma Oncogene Homolog A), a key transcription factor of beta-cell maturation. Analysis of the expression of antioxidant enzymes in pancreatic islet and 4-hydroxynonenal (4-HNE) (a specific marker of lipid peroxidation) staining revealed that oxidative stress occurred in mice lacking p43. Lastly, administration of antioxidants cocktail to p43-/- pregnant mice restored a normal islet density but failed to ensure an insulin secretion in response to glucose. Our findings demonstrated that p43 drives the maturation of beta cells via its induction of transcription factor MafA during the critical postnatal window.

Excessive fat consumption leads to the development of ectopic adipose tissues, affecting the organs they surround. Peripancreatic adipose tissue is implicated in glucose homeostasis regulation and can be impaired in obesity. High palm oil consumption’s effects on health are still debated. We hypothesised that crude and refined palm oil high-fat feeding may have contrasting effects on peripancreatic adipocyte hypertrophy, inflammation and lipid oxidation compound production in obese rats. In Wistar rats, morphological changes, inflammation and isoprostanoid production following oxidative stress were assessed in peripancreatic adipose tissue after 12 weeks of diets enriched in crude or refined palm oil or lard (56% energy from fat in each case) versus a standard chow diet (11% energy from fat). Epididymal white and periaortic brown adipose tissues were also included in the study. A refined palm oil diet disturbed glucose homeostasis and promoted lipid deposition in periaortic locations, as well as adipocyte hypertrophy, macrophage infiltration and isoprostanoid (5-F2c-isoprostane and 7(RS)-ST-Δ8-11-dihomo-isofuran) production in peripancreatic adipose tissue. Crude palm oil induced a lower impact on adipose deposits than its refined form and lard. Our results show that the antioxidant composition of crude palm oil may have a protective effect on ectopic adipose tissues under the condition of excessive fat intake.

In addition to the major fatty acids widely studied, our diet contains many bioactive fatty acids less frequently investigated such as n-3 docosapentaenoic acid (n-3 DPA), natural trans fatty acids, conjugated fatty acids (CLAs), furan fatty acids (FuFAs), branched chain fatty acids (BCFAs) and fatty acid esters of hydroxyl fatty acids (FAHFAs). Many of them may have beneficial health effects, particularly in the prevention of cardiovascular diseases, inflammation and metabolic disorders such as diabetes. This review aims to give a brief overview of the current knowledge on these lipids. Thus, information about biosynthesis, food and tissue content, daily intake, biological and potential health effects of these fatty acids is provided., Parallèlement aux acides gras prépondérants qui sont largement étudiés, notre alimentation contient de nombreux acides gras bioactifs moins fréquemment considérés tels que l’acide docosapentaénoïque n-3 (n-3 DPA), des acides gras trans naturels, des acides gras conjugués (CLAs), des acides gras furaniques (FuFAs), des acides gras à chaîne ramifiée (BCFAs) et des esters d’acides gras hydroxylés (FAHFAs). Nombreux d’entre eux peuvent avoir des effets bénéfiques sur la santé, notamment dans la prévention des maladies cardiovasculaires, de l’inflammation et des troubles métaboliques tels que le diabète. Cette revue vise à donner un bref aperçu des connaissances actuelles sur ces lipides. Ainsi, des informations sur la biosynthèse, les teneurs tissulaires et dans les aliments, l’apport alimentaire quotidien, les effets biologiques et les effets santé potentiels de ces acides gras sont rapportés.

Branched fatty acid esters of hydroxy fatty acids (FAHFAs) are endogenous lipids reported to have antidiabetic and anti-inflammatory effects. Since skeletal muscle is a major target for insulin, the aim of this study is to explore for the first time the influence of several FAHFAs in C2C12 myoblasts and in skeletal muscle phenotype in mice. Here, we show that eleven FAHFAs belonging to different families inhibit C2C12 myoblast proliferation. In addition, all FAHFAs decreased mitochondrial cytochrome c oxidase activity without affecting reactive oxygen species production and the mitochondrial network. During C2C12 myoblasts differentiation, we found that two of the most active lipids, 9-PAHPA and 9-OAHPA, did not significantly affect the fusion index and the expression of myosin heavy chains. However, we found that three months&rsquo, intake of 9-PAHPA or 9-OAHPA in mice increased the expression of more oxidative myosin in skeletal muscle without affecting skeletal muscle mass, number, and mean fiber area, mitochondrial activity, and oxidative stress parameters. In conclusion, our study indicated that the eleven FAHFAs tested decreased the proliferation rate of C2C12 myoblasts, probably through the inhibition of mitochondrial activity. In addition, we found that 9-PAHPA or 9-OAHPA supplementation in mice induced a switch toward a more oxidative contractile phenotype of skeletal muscle. These data suggest that the increase in insulin sensitivity previously described for these two FAHFAs is of muscular origin.

International audience; It has recently emerged that myokines may be an important skeletal muscle adaptive response to obesogenic diets in sedentary subjects (who do not exercise). This study aimed to assess the influence of various high fat (HF) diets rich in either crude palm oil (cPO), refined palm oil (rPO), olive oil (OO) or lard on the modulation of myokine gene expression in the gastrocnemius. Five groups of 8 rats were each fed HF or control diet for 12 weeks. Systemic parameters concerning glucose, insulin, inflammation, cholesterol, triglycerides (TG) and transaminases were assessed by routine methods or ELISA. Akt and ACC phosphorylation were analyzed by WB in the soleus. Mitochondrial density, inflammation, and the gene expression of 17 myokines and the apelin receptor (Apj) were assessed by qPCR in the gastrocnemius. We found that HF diet-fed rats were insulin resistant and Akt phosphorylation decreased in the soleus muscle, but without any change in Glut4 gene expression. Systemic (IL-6) and muscle inflammation (NFκB and IκB) were not affected by the HF diets as well as TBARS, and ASAT level was enhanced with OO diet. Soleus pACC phosphorylation and gastrocnemius mitochondrial density were not significantly altered. The gene expression of some myokines was respectively increased (myostatin and Il-15) and decreased (Fndc5 and apelin) with the HF diets, whatever the type of fat used. The gene expression of two myokines with anti-inflammatory properties, Il-10 and myonectin, was dependent on the type of fat used and was most increased respectively with cPO or both rPO and OO diets. In conclusion, high-fat diets can differentially modulate the expression of some myokines, either in a dependent manner or independently of their composition.

International audience; Purpose: Fatty acid esters of hydroxy fatty acids (FAHFAs) are a large family of endogenous bioactive lipids. To date, most of the studied FAHFAs are branched regioisomers of Palmitic Acid Hydroxyl Stearic Acid (PAHSA) that were reported to possess anti-diabetic and anti-inflammatory activity in humans and rodents. Recently, we have demonstrated that 9-PAHPA or 9-OAHPA intake increased basal metabolism and enhanced insulin sensitivity in healthy control diet-fed mice but induced liver damage in some mice. The present work aims to explore whether a long-term intake of 9-PAHPA or 9-OAHPA may have similar effects in obesogenic diet-fed mice. Methods: C57Bl6 mice were fed with a control or high fat-high sugar (HFHS) diets for 12 weeks. The HFHS diet was supplemented or not with 9-PAHPA or 9-OAHPA. Whole-body metabolism was explored. Glucose and lipid metabolism as well as mitochondrial activity and oxidative stress status were analyzed. Results: As expected, the intake of HFHS diet led to obesity and lower insulin sensitivity with minor effects on liver parameters. The long-term intake of 9-PAHPA or 9-OAHPA modulated favorably the basal metabolism and improved insulin sensitivity as measured by insulin tolerance test. On the contrary to what we have reported previously in healthy mice, no marked effect for these FAHFAs was observed on liver metabolism of obese diabetic mice. Conclusion: This study indicates that both 9-PAHPA and 9-OAHPA may have interesting insulin-sensitizing effects in obese mice with lower insulin sensitivity.

International audience; Branched fatty acid esters of hydroxy fatty acids (FAHFAs) are a new family of endogenous lipids recently discovered. Several studies reported that some FAHFAs have antidiabetic and anti-inflammatory effects. The objective of this study was to explore the impact of two FAHFAs, 9-PAHPA or 9-OAHPA, on the metabolism of mice. C57Bl/6J male mice, 6 weeks old, were divided into 3 groups of 10 mice each. One group received a control diet and the two others groups received the control diet supplemented with 9-PAHPA or 9-OAHPA for 12 weeks. Mouse weight and body composition were monitored throughout the study. Some days before euthanasia, energy expenditure, glucose tolerance and insulin sensitivity were also determined. After sacrifice, blood and organs were collected for relevant molecular, biochemical and histological analyses. Although high intake of 9-PAHPA or 9-OAHPA increased basal metabolism, it had no direct effect on body weight. Interestingly, the 9-PAHPA or 9-OAHPA intake increased insulin sensitivity but without modifying glucose tolerance. Nevertheless, 9-PAHPA intake induced a loss of glucose-stimulated insulin secretion. Surprisingly, both studied FAHFAs induced hepatic steatosis and fibrosis in some mice, which were more marked with 9-PAHPA. Finally, a slight remodeling of white adipose tissue was also observed with 9-PAHPA intake. In conclusion, the long-term high intake of 9-PAHPA or 9-OAHPA increased basal metabolism and insulin sensitivity in healthy mice. However, this effect, highly likely beneficial in a diabetic state, was accompanied by manifest liver damage in certain mice that should deserve special attention in both healthy and pathological studies.

International audience; Inflammation and oxidative stress are thought to be involved in, or associated with, the development of obesity, dyslipidemia, hepatic steatosis, and insulin resistance. This work was designed to determine the evolution of inflammation and oxidative stress during onset and progression of hepatic steatosis and glucose intolerance. Seventy-five male Wistar rats were divided to control and high-fat high-fructose (HFHFr) groups. A subgroup of each group was sacrificed at 4, 8, 12, 16, and 20 weeks. HFHFr-fed rats exhibited overweight, glucose intolerance, and hepatic steatosis with increased contents of hepatic diacylglycerols and ceramides. The HFHFr diet increased hepatic interleukin 6 (IL-6) protein and adipose tissue CCL5 gene expression and hepatic nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity but not mitochondrial reactive oxygen species (ROS) production. The HFHFr diet decreased plasma and liver levels of isoprostanoid metabolites as well as plasma thiobarbituric acid-reactive substance (TBARS) levels. Hepatic glutathione content was decreased with a moderate decrease in superoxide dismutase (SOD) and glutathione peroxidase (GPx) with the HFHFr diet. Overall, HFHFr diet led to hepatic lipid accumulation and glucose intolerance, which were accompanied by only moderate inflammation and oxidative stress. Most of these changes occurred at the same time and as early as 8 or 12 weeks of diet treatment. This implies that oxidative stress may be the result, not the cause, of these metabolic alterations, and suggests that marked hepatic oxidative stress should probably occur at the end of the steatotic stage to result in frank insulin resistance and steatohepatitis. These findings need to be further evaluated in other animal species as well as in human studies.

Myostatin (Mstn) inactivation or inhibition is considered as a promising treatment for various muscle-wasting disorders because it promotes muscle growth. However, myostatin-deficient hypertrophic muscles show strong fatigability associated with abnormal mitochondria and lipid metabolism. Here, we investigated whether endurance training could improve lipid metabolism and mitochondrial membrane lipid composition in mice where the Mstn gene was genetically ablated (Mstn−/- mice). In Mstn−/- mice, 4 weeks of daily running exercise sessions (65–70% of the maximal aerobic speed for 1 h) improved significantly aerobic performance, particularly the endurance capacity (up to +280% compared with untrained Mstn−/- mice), to levels comparable to those of trained wild type (WT) littermates. The expression of oxidative and lipid metabolism markers also was increased, as indicated by the upregulation of the Cpt1, Ppar-δ and Fasn genes. Moreover, endurance training also increased, but far less than WT, citrate synthase level and mitochondrial protein content. Interestingly endurance training normalized the cardiolipin fraction in the mitochondrial membrane of Mstn−/- muscle compared with WT. These results suggest that the combination of myostatin inhibition and endurance training could increase the muscle mass while preserving the physical performance with specific effects on cardiolipin and lipid-related pathways.

Metabolic syndrome components, including obesity, dyslipidemia and impaired glucose homeostasis, become a major public health issue. Muscles play a predominant role in insulin-mediated glucose uptake, and high fat diets may negatively affect muscle function and homeostasis. This work aimed to study the time-course of muscle lipid accumulation, oxidative stress and mitochondrial dysfunction and their association to impaired glucose homeostasis in rats fed an obesogenic diet. Male Wistar rats were fed with a standard or a high fat/high fructose (HFHFr) diet and sacrificed on 4, 8, 12, 16, 20 weeks. Rats fed the HFHFr diet developed mild overweight, increased liver and adipose tissue weights and glucose intolerance. The impaired glucose homeostasis increased gradually with the HFHFr diet to become significant on the 12th and 16th weeks of diet. In parallel, the muscle lipid composition showed an increase in the saturated fatty acids and the monounsaturated fatty acids with a marked decrease in the polyunsaturated fatty acids. The HFHFr diet also increased muscle contents of both diacylglycerols and Ceramides. Surprisingly, HFHFr diet did not induce major muscle mitochondrial dysfunction or oxidative stress. These results indicate that muscle lipid alterations, as well as impaired glucose homeostasis occur as early as the 8th week of HFHFr diet, increase to reach a plateau around the 12th-16th weeks of diet, and then attenuate towards the end of study. At these diet treatment durations, muscle mitochondrial activity and oxidative stress remained unchanged and do not seem to have a major role in the observed impaired glucose homeostasis.

International audience; Purpose Palm (PO) and olive oils (OO) are the two most consumed and/or used oils in the world for food elaboration. These oils should not be confused with the solid palm stearin which is widely used in pastry making. Large number of studies was reported dealing with adverse/beneficial cardiovascular effects of PO and OO, whereas few studies were conducted to compare their potential effects on hepatic steatosis and liver lipid metabolism. The aim of this study was to compare the metabolic effects of high intake of POs (both crude and refined) and virgin OO on surrogate parameters of glucose tolerance, hepatic lipid metabolism and liver integrity. Methods Thirty-two young male Wistar rats were divided into four equal groups and fed either control diet (11% energy from fat) or three high-fat diets rich in crude or refined POs or in OO (56% energy from fat), during 12 weeks. Systemic blood and liver biochemical parameters linked to glucose and lipid metabolism as well as hepatic steatosis and liver fatty acid composition were explored. The inflammation and oxidative stress status as well as the expression of several genes/proteins were also analyzed. ResultsThe major effects of POs intake concerned glucose metabolism and liver fatty acid composition, whereas the major effects of OO intake concerned hepatic TG accumulation, inflammation, and cytolysis. Conclusions In conclusion, high dietary intake of PO compromises glucose tolerance whereas high dietary intake of OO compromises hepatic lipid composition and liver integrity. However, adverse hepatic effects of OO observed in this study may not be transposed to human since, (a) the rodent model could lead to different effects than those observed in humans and (b) the average normal OO amounts ingested in the population are lower than those corresponding to a high-fat diet. So, further studies are needed to determine a maximum non-invasive dietary intake of OO.

Pentadecanoic acid (C15:0) and heptadecanoic acid (C17:0) have been described as dietary biomarkers of dairy-fat consumption with varying degrees of reliability between studies. It remains unclear how the total amount of dietary fat; one of the main confounding factors in these biomarker investigations, affects C15:0 and C17:0 circulating compositions independently to their relative intake. Additionally, it is unknown how changes in the dietary total-fat affects other fatty acids in circulation. Through two dietary studies with different total-fat levels but maintaining individual fatty acid compositions we were able to see how the dietary total-fat affects the fatty acids in circulation. We saw that there was a significant, proportionate, and robust decrease in the endogenous C15:0 levels with an increase in dietary total-fat. However, there was an increase in the circulating C17:0 compositions as the total-fat increased. To conclude, the dietary total-fat content and fat-type have a very complex influence on the relative compositions of circulating fatty acids, which are independent to the actual dietary fatty acid composition. Knowing how to manipulate circulating C15:0 and C17:0 composition is far-reaching in nutritional/pathological research as they highlight a dietary route to attenuate the development of metabolic disease (both by reducing risk and improving prognosis).

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.

Fatty acid hydroxylated fatty acid esters (FAHFAs) are a family of endogenous lipids recently rediscovered by Professor Kahn's team (Yore et al., 2014). Several studies have shown that FAHFAs improve glucose tolerance, sensitivity to and secretion of insulin and have anti-inflammatory effects. FAHFAs are found in blood and many tissues in humans and in rodents, as well as in breast milk and in food. They are synthesized de novo in tissues, however the biosynthesis and degradation pathways of these bioactive lipids are not yet elucidated. Several studies show that the levels of FAHFAs are regulated in mice and humans by physiological and physiopathological conditions such as fasting, obesity and insulin resistance. In this review, we will present the current state of the art concerning FAHFAs and in particular, the biological effects of these bioactive lipids.; Les esters d’acides gras hydroxylés (FAHFAs) sont une famille de lipides endogènes récemment découverts par l’équipe du Pr Kahn (Yore et al., 2014). Plusieurs travaux montrent que les FAHFAs améliorent la tolérance au glucose, la sensibilité à l’insuline et sa sécrétion, et possèdent des effets anti-inflammatoires. Les FAHFAs sont présents dans le sang et dans de nombreux tissus chez l’homme et chez le rongeur, mais également dans le lait maternel et dans les aliments. Les FAHFAs sont synthétisés de novo dans les tissus, cependant leurs voies de biosynthèse et de dégradation ne sont pas élucidées à ce jour. Les taux de FAHFAs dans l’organisme seraient modifiés par des altérations physiologiques et physiopathologiques tels le jeûne, l’obésité et l’insulinorésistance. Dans cette revue, nous ferons un bilan sur l’état des connaissances concernant les FAHFAs et présenterons en particulier les effets biologiques de ces lipides bioactifs connus à l’heure actuelle

Natural deep eutectic solvents (NaDES) are new natural solvents in green chemistry that in some cases have been shown to allow better extraction of plant bioactive molecules compared to conventional solvents and higher phenolic compound absorption in rodents. However, there is a serious lack of information regarding their in vivo safety. The purpose of this study wasto verify the safety of a NaDES (glycerol:betaine (mole ratio 2:1) + 10% (v/v) of water) extract from green coffee beans, rich in polyphenols. Twelve 6-week-old male Wistar rats were randomized into two groups of 6 animals each and twice daily gavaged for 14 days either with 3 mL of water or 3 mL of phenolic NaDES extract. Oral administration of phenolic NaDES extract induced mortality in two rats. In addition, it induced excessive water consumption, reduced dietary intake and weight loss, hepatomegaly, and plasma oxidative stress associated with high blood lipid levels. In conclusion, this work demonstrated the toxicity of oral administration of the selected NaDES under a short-term condition. This occurs despite the fact that this NaDES extract contains polyphenols, whose beneficial effects have been shown. Therefore, complementary work is needed tofind the best dose and formulation of NaDES that are safe for the environment and animals and ultimately for humans.

Thyroid hormone is a major regulator of metabolism and mitochondrial function. Thyroid hormone also affects reactions in almost all pathways of lipids metabolism and as such is considered as the main hormonal regulator of lipid biogenesis. The aim of this study was to explore the possible involvement of p43, a 43 Kda truncated form of the nuclear thyroid hormone receptor TRα1 which stimulates mitochondrial activity. Therefore, using mouse models overexpressing p43 in skeletal muscle (p43-Tg) or lacking p43 (p43-/-), we have investigated the lipid composition in quadriceps muscle and in mitochondria. Here, we reported in the quadriceps muscle of p43-/- mice, a fall in triglycerides, an inhibition of monounsaturated fatty acids (MUFA) synthesis, an increase in elongase index and an decrease in desaturase index. However, in mitochondria from p43-/- mice, fatty acid profile was barely modified. In the quadriceps muscle of p43-Tg mice, MUFA content was decreased whereas the unsaturation index was increased. In addition, in quadriceps mitochondria of p43-Tg mice, we found an increase of linoleic acid level and unsaturation index. Last, we showed that cardiolipin content, a key phospholipid for mitochondrial function, remained unchanged both in quadriceps muscle and in its mitochondria whatever the mice genotype. In conclusion, this study shows that muscle lipid content and fatty acid profile are strongly affected in skeletal muscle by p43 levels. We also demonstrate that regulation of cardiolipin biosynthesis by the thyroid hormone does not imply p43.

International audience; The prevalence of metabolic syndrome components, such as obesity, glucose intolerance and hepatic steatosis, is rapidly increasing and becoming a major issue of public health. The present work was designed to determine the effects of Spirulina platensis (Sp) algae and silicon-enriched Sp on major metabolic syndrome components in obesogenic diet-fed rats. Forty male Wistar rats were divided into 4 groups. Ten rats were fed a control diet and 30 rats were fed a high fat (HF) diet. The HF groups were divided into three groups and supplemented with placebo or Sp or Si-enriched Sp for 12 weeks. Dietary intake and body weight were recorded. Oral glucose tolerance test and surrogate metabolic syndrome (insulin, leptin, adiponectin and lipids), mitochondrial function (enzymatic activity of respiratory chain complexes and β-hydroxyacyl-CoA dehydrogenase), NADPH oxidase activity and several long-established oxidative stress markers were measured in the blood and liver. The HF diet induced obesity, glucose intolerance, hepatic steatosis and huge metabolic alterations, associated with higher NADPH oxidase activity and lower hepatic sulfhydryl group and glutathione contents. Otherwise, the Sp and Sp + Si supplements showed some interesting effects on rat characteristics and particularly on blood and hepatic metabolic parameters. Indeed, the intake of Sp or Sp + Si mainly improved glucose tolerance and decreased the enzymatic activity of hepatic NADPH oxidase. Overall, Si supplementation of spirulina does not appear to have more beneficial effects than spirulina alone. Other experiments with different species of rats/mice, different diets or different durations of diet intake should be undertaken to confirm or invalidate these results.

Cardiolipin (CL) is a phospholipid at the heart of mitochondrial metabolism, which plays a key role in mitochondrial function and bioenergetics. Among mitochondrial activity regulators, SIRT3 plays a crucial role in controlling the acetylation status of many enzymes participating in the energy metabolism in particular concerning lipid metabolism and fatty acid oxidation. Data suggest that possible connection may exist between SIRT3 and CL status that has not been evaluated in skeletal muscle. In the present study, we have characterized skeletal muscle lipids as well as mitochondrial lipids composition in mice overexpressing long (SIRT3-M1) and short (SIRT3-M3) isoforms of SIRT3. Particular attention has been paid for CL. We reported no alteration in muscle lipids content and fatty acids composition between the two mice SIRT3 strains and the control mice. However, mitochondrial CL content was significantly decreased in SIRT3-M3 mice and associated to an upregulation of tafazzin gene expression. In addition, mitochondrial phospholipids and fatty acids composition was altered with an increase in the PC/PE ratio and arachidonic acid content and a reduction in the MUFA/SFA ratio. These modifications in mitochondrial membrane composition are associated with a reduction in the enzymatic activities of mitochondrial respiratory chain complexes I and IV. In spite of these mitochondrial enzymatic alterations, skeletal muscle mitochondrial respiration remained similar in SIRT3-M3 and control mice. Surprisingly, none of those metabolic alterations were detected in mitochondria from SIRT3-M1 mice. In conclusion, our data indicate a specific action of the shorter SIRT3 isoform on lipid mitochondrial membrane biosynthesis and functioning.

Myostatin (Mstn) deficiency leads to skeletal muscle overgrowth and Mstn inhibition is considered as a promising treatment for muscle-wasting disorders. Mstn gene deletion in mice also causes metabolic changes with decreased mitochondria content, disturbance in mitochondrial respiratory function and increased muscle fatigability. However the impact of MSTN deficiency on these metabolic changes is not fully elucidated. Here, we hypothesized that lack of MSTN will alter skeletal muscle membrane lipid composition in relation with pronounced alterations in muscle function and metabolism. Indeed, phospholipids and in particular cardiolipin mostly present in the inner mitochondrial membrane, play a crucial role in mitochondria function and oxidative phosphorylation process. We observed that Mstn KO muscle had reduced fat membrane transporter levels (FAT/CD36, FABP3, FATP1 and FATP4) associated with decreased lipid oxidative pathway (citrate synthase and β-HAD activities) and impaired lipogenesis (decreased triglyceride and free fatty acid content), indicating a role of mstn in muscle lipid metabolism. We further analyzed phospholipid classes and fatty acid composition by chromatographic methods in muscle and mitochondrial membranes. Mstn KO mice showed increased levels of saturated and polyunsaturated fatty acids at the expense of monounsaturated fatty acids. We also demonstrated, in this phenotype, a reduction in cardiolipin proportion in mitochondrial membrane versus the proportion of others phospholipids, in relation with a decrease in the expression of phosphatidylglycerolphosphate synthase and cardiolipin synthase, enzymes involved in cardiolipin synthesis. These data illustrate the importance of lipids as a link by which MSTN deficiency can impact mitochondrial bioenergetics in skeletal muscle.

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.

International audience; While myostatin gene deletion is a promising therapy to fight muscle loss during aging, this approach induces also skeletal muscle metabolic changes such as mitochondrial deficits, redox alteration and increased fatigability. In the present study, we evaluated the effects of aging on these features in aged wild-type (WT) and mstn knockout (KO) mice. Moreover, to determine whether an enriched-antioxidant diet may be useful to prevent age-related disorders, we orally administered to the two genotypes a melon concentrate rich in superoxide dismutase for 12 weeks. We reported that mitochondrial functional abnormalities persisted (decreased state 3 and 4 of respiration; p

International audience; No data are reported on changes in mitochondrial membrane phospholipids in non-alcoholic fatty liver disease. We determined the content of mitochondrial membrane phospholipids from rats with non alcoholic liver steatosis, with a particular attention for cardiolipin (CL) content and its fatty acid composition, and their relation with the activity of the mitochondrial respiratory chain complexes. Different dietary fatty acid patterns leading to steatosis were explored.With high-fat diet, moderate macrosteatosis was observed and the liver mitochondrial phospholipid class distribution and CL fatty acids composition were modified. Indeed, both CL content and its C18:2n-6 content were increased with liver steatosis. Moreover, mitochondrial ATP synthase activity was positively correlated to the total CL content in liver phospholipid and to CL C18:2n-6 content while other complexes activity were negatively correlated to total CL content and/or CL C18:2n-6 content of liver mitochondria. The lard-rich diet increased liver CL synthase gene expression while the fish oil-rich diet increased the (n-3) polyunsaturated fatty acids content in CL. Thus, the diet may be a significant determinant of both the phospholipid class content and the fatty acid composition of liver mitochondrial membrane, and the activities of some of the respiratory chain complex enzymes may be influenced by dietary lipid amount in particular via modification of the CL content and fatty acid composition in phospholipid.

Contact: christelle.ramonatxo@univ-montp1.fr; International audience; Lack of myostatin alters intermyofibrillar mitochondria activity, unbalances redox status, and impairs tolerance to chronic repetitive contractions in muscle. Am J Physiol Endocrinol Metab 302: E1000-E1008, 2012. First published February 7, 2012; doi:10.1152/ajpendo.00652.2011.-Loss of myostatin (mstn) function leads to a decrease in mitochondrial content, a reduced expression of cytochrome c oxidase, and a lower citrate synthase activity in skeletal muscle. These data suggest functional or ultrastructural mitochondrial abnormalities that can impact on muscle endurance characteristics in such phenotype. To address this issue, we investigated subsarcolemmal and intermyofibrillar (IMF) mitochondrial activities, skeletal muscle redox homeostasis, and muscle fiber endurance quality in mstn-deficient mice [ mstn knockout (KO)]. We report that lack of mstn induced a decrease in the coupling of IMF mitochondria respiration, with significantly higher basal oxygen consumption. No lysis of mitochondrial cristae or excessive swelling were observed in mstn KO mice compared with wild-type (WT) mice. Concerning redox status, mstn KO gastrocnemius exhibited a significant decrease in lipid peroxidation levels (-56%; P < 0.01 vs. WT) together with a significant upregulation of the antioxidant glutathione system. In contrast, superoxide dismutase and catalase activities were altered in mstn KO, gastrocnemius and soleus with a reduction of up to 80% compared with WT animals. The force production observed after contractile endurance test was significantly lower in extensor digitorum longus and soleus muscles of mstn KO mice compared with the controls (17 +/- 3 and 36 +/- 5% vs. 28 +/- 4 and 56 +/- 5%, respectively, P < 0.05). Together, these findings indicate that, besides an increased skeletal muscle mass, genetic mstn inhibition has differential effects on redox homeostasis and mitochondrial function that would have functional consequences on muscle response to endurance exercise.

An increased rate of bone turnover increases risk of osteoporotic fracture later in life. The concentration of 25-hydroxyvitamin D that contributes to an elevated rate of bone turnover in older adults is unclear. The objective of this study was to investigate the associations between 25-hydroxyvitamin D and biochemical markers of bone turnover in an older, pan-European cohort. 25-hydroxyvitamin D and serum markers of bone-formation (osteocalcin and bone-specific alkaline phosphatase) were assessed by ELISA, while urinary markers of bone-resorption (pyridinoline and deoxypyridinoline) were assessed by HPLC. Six percent, 36 %, and 64 % of subjects had 25-hydroxyvitamin D concentrations < 25, < 50, and < 80 nmol/L throughout the year, respectively. 25-hydroxyvitamin D was significantly and inversely correlated with serum bone-specific alkaline phosphatase (r = 0.119; p = 0.022) and urinary pyridinoline (r = 0.207; p < 0.0001) and deoxypyridinoline (r = 0.230; p < 0.0001). Stratification on the basis of tertiles [T] of 25-hydroxyvitamin D (< 47.6 [T1]; 47.6 - 85.8 [T2]; > 85.8 [T3] nmol/L), showed that urinary pyridinoline and deoxypyridinoline were significantly lower in subjects in the 2nd and 3rd compared to the 1st tertile (p < 0.015). Low vitamin D status (< 50 nmol/L) was associated with an increased rate of bone turnover in this older pan-European cohort.

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 andtrans-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 dietv.basal and lard-rich diets, and PLtrans-FA increased with lard dietv.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.

ObjectiveOlder 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.SubjectsHealthy volunteers (n 387) aged 55–87 years were recruited.SettingVolunteers 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.DesignMood 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.ResultsMixed 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.ConclusionsThese results suggest that zinc does not benefit mood in healthy older people.

The dysmetabolic iron overload syndrome (DIOS) is a common disorder but its origin remains unclear.A case-control study was conducted to compare intestinal absorption of iron in 16 men with DIOS (age 53 +/- 11 years, serum ferritin 750 +/- 372 microg/l, hepatic iron 78 +/- 25 micromol/g) and in 32 age-matched controls with normal body iron stores (16 overweight subjects and 16 lean subjects). Intestinal absorption was calculated as the area under the curve (AUC) of 58Fe administered orally and correlated with plasma hepcidin and with insulin resistance parameters including HOMA.Intestinal iron absorption was lower in DIOS (AUC = 22.4 +/- 15.9 microg/l/h) compared to both overweight controls (AUC = 40.5 +/- 29.4 microg/l/h, p=0.04) and to lean controls (AUC = 102.5 +/- 113.5 microg/l/h, p0.01). There was an inverse correlation between intestinal iron absorption and plasma hepcidin (r = -0.61, p0.001), HOMA (r = -0.35, p = 0.01) and C reactive protein (r = -0.52, p0.001).In overweight subjects with normal iron stores, iron absorption is decreased through hepcidin upregulation. In patients with DIOS, this decrease is more pronounced due to an additional effect of iron excess on circulating hepcidin levels.

The aims of this study were to investigate the relationship between salivary cortisol, stress and mood and to look at the circadian rhythms of positive (PA) and negative (NA) mood in older adults. The participants were 41 healthy adults aged 55-69 years, recruited in Northern Ireland as part of the European Commission-funded Zenith project. Salivary cortisol samples were obtained twice a day (2.30 p.m. and 10.30 p.m.) for 7 consecutive days in conjunction with momentary measures of positive (PA) and negative mood (NA), using PANAS and a trait measure of perceived stress (Perceived Stress Scale). Salivary cortisol levels were measured using an enzyme-linked immunoassay kit. Higher perceived stress levels were associated with lower afternoon PA (r = -0.46, p = 0.003) and higher afternoon (r = 0.43, p = 0.007) and evening (r = 0.45, p = 0.004) NA. Lower afternoon PA was correlated with higher evening cortisol concentrations (r = -0.47, p = 0.002). Greater afternoon PA variability was associated with higher evening cortisol concentrations (r = 0.38, p = 0.015). A high intra-class correlation between cortisol and positive mood was found (r = 0.67, p = 0.009). Previously established rhythms for positive and negative mood were confirmed. Interestingly, there was no association between salivary cortisol levels and perceived stress in these healthy older adults. Further, more extensive research is required to better understand the apparent interplay between these variables and ageing. (c) 2007 Elsevier B.V. All rights reserved.

Aging is associated with alterations in the immune system, effects which may be exacerbated by inadequate zinc (Zn) status. We examined the relationship between Zn status and markers of immunity and the effect of supplementation with 15 mg or 30 mg Zn/d for 6 months on immune status in healthy individuals. Zn status was assessed by dietary intake and biochemical indices. Immune status was assessed by multiple flow cytometric methods. At baseline, Zn concentration was positively associated with lymphocyte subpopulation counts and T-lymphocyte activation. Zn supplementation of 30 mg/d significantly lowered B-lymphocyte count, albeit at month 3 only. Lower doses of Zn (15 mg Zn/d) significantly increased the ratio of CD4 to CD8 T lymphocytes at month 6. Overall, these findings suggest that total Zn intake (diet plus supplementation) of up to 40 mg Zn/d do not have significant long-term effects on immune status in apparently healthy persons aged 55-70 years.

International audience; Myostatin (mstn) blockade, resulting in muscle hypertrophy, is a promising therapy to counteract age-related muscle loss. However, oxidative and mitochondrial deficit observed in young mice with myostatin inhibition could be detrimental with aging. The aim of this study was (a) to bring original data on metabolic and mitochondrial consequences of mstn inhibition in old mice, and (b) to examine whether 4-weeks of AICAR treatment, a pharmacological compound known to upregulate oxidative metabolism, may be useful to improve exercise capacity and mitochondrial deficit of 20-months mstn KO versus wild-type (WT) mice. Our results show that despite the enlarged muscle mass, the oxidative and mitochondrial deficit associated with reduced endurance running capacity is maintained in old mstn KO mice but not worsened by aging. Importantly, AICAR treatment induced a significant beneficial effect on running limit time only in old mstn KO mice, with a marked increase in PGC-1α expression and slight beneficial effects on mitochondrial function. We showed that AICAR effects were autophagy-independent. This study underlines the relevance of aged muscle remodelling by complementary approaches that impact both muscle mass and function, and suggest that mstn inhibition and aerobic metabolism activators should be co-developed for delaying age-related deficits in skeletal muscle.

Cardiolipin (CL), a unique mitochondrial phospholipid, plays a key role in several processes of mitochondrial bioenergetics as well as in mitochondrial membrane stability and dynamics. The present study was designed to determine the effect of MitoQ, a mitochondrial-targeted antioxidant, on the content of liver mitochondrial membrane phospholipids, in particular CL, and its fatty acid composition in obesogenic diet-fed rats.To do this, twenty-four 6week old male Sprague Dawley rats were randomized into three groups of 8 animals and fed for 8weeks with either a control diet, a high fat diet (HF), or a HF diet with MitoQ (HF+MitoQ). Phospholipid classes and fatty acid composition were assayed by chromatographic methods in liver and liver mitochondria. Mitochondrial bioenergetic function was also evaluated. While MitoQ had no or slight effects on total liver fatty acid composition and phospholipid classes and their fatty acid composition, it had major effects on liver mitochondrial phospholipids and mitochondrial function. Indeed, MitoQ both increased CL synthase gene expression and CL content of liver mitochondria and increased 18:2n-6 (linoleic acid) content of mitochondrial phospholipids by comparison to the HF diet. Moreover, mitochondrial CL content was positively correlated to mitochondrial membrane fluidity, membrane potential and respiration, as well as to ATP synthase activity, while it was negatively correlated to mitochondrial ROS production.These findings suggest that MitoQ may decrease pathogenic alterations to CL content and profiles, thereby preserving mitochondrial function and attenuating the development of some of the features of metabolic syndrome in obesogenic diet-fed rats.

Resume Le cardiolipide (CL) est un phospholipide exclusivement present dans la membrane mitochondriale et joue un role cle dans plusieurs processus de bioenergetique mitochondriale, ainsi que dans la stabilite et la dynamique de la membrane mitochondriale. En raison de sa richesse en acides gras polyinsatures (en particulier en acide linoleique), le CL est tres sensible a l’attaque par les radicaux libres produits par la mitochondrie. L’oxydation du CL a des consequences majeures sur le fonctionnement de la mitochondrie, en particulier la phosphorylation oxydative et la production d’ATP. Par ailleurs, les regimes alimentaires plus ou moins riches en graisses peuvent modifier la composition lipidique de la membrane mitochondriale, y compris la teneur en CL et sa composition en acides gras, et ces modifications peuvent par la suite alterer le fonctionnement de la mitochondrie. Or, les regimes alimentaires riches en graisses sont associes a la steatose hepatique et a l’insulino-resistance, deux problemes majeurs de sante publique. L’objectif de cet article est de faire le point sur les connaissances actuelles concernant le role du CL dans les pathologies nutritionnelles liees a une surcharge en lipides.

International audience; Fibers and potassium (K) organic salts in plant foods are liable to affect Ca and Mg balance at digestive and renal levels, respectively. K organic salts could counteract the acidifying effects of western diets and consequences of excess NaCl. Aim of the study: To study this question, male rats were adapted to a basal acidifying low-K (LK) diet, or to diets supplemented with a fiber mix (LK/F), or K citrate (HK) or both (HK/F). Results: HK and HK/F diets displayed a marked alkalinizing effect in urine and promoted citraturia, but this effect was not modulated by fibers. The effect of fibers on Ca digestive absorption was more potent than K citrate effect on Ca renal excretion. In contrast, K citrate effect on kidney Mg excretion was more effective than that of fibers on Mg digestive absorption, a maximal effect on Mg balance was observed in rats fed the HK/F diet. Digestive fermentations in rats fed the LK/F diet were characterized by high-propionic acid fermentations and succinate accumulation. In rats adapted to the HK/F diet, K citrate supplementation depressed succinate and increased butyrate concentrations. Conclusion: Organic anions arising from digestive fermentations seem to be not directly involved in the alkalinizing effects of plant foods. Fibers and organic K salts exert distinct effects on Ca and Mg metabolism, but with interesting interactions as to Mg balance, digestive fermentations and urine pH.

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 waterad libitumfor 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.

Background: Age-related decline in taste acuity may be both a cause and an effect of depleted zinc and/or increased zinc requirement. Objective: The aim of this study was to explore associations between zinc status and taste acuity in healthy older European adults aged 55-90 y. Sample: Volunteers were recruited within Italy (n = 108 aged 70-90 y), the United Kingdom (UK) (n = 93 aged 55-70) and two regions of France (n = 186), Grenoble (aged 70-90 y) and Clermont-Ferrand (aged 55-70 y). Methods: A signal detection theory approach was adopted, employing a three-alternative, forced-choice procedure. The data were converted to R-indices and bivariate correlations were computed to explore relationships between serum zinc, erythrocyte zinc and taste acuity. ANOVA was undertaken to determine regional differences in zinc status. Results: Higher erythrocyte zinc status was associated with better acuity for salt (sodium chloride) taste in the sample as a whole (P = 0.012) (n = 385). Higher serum zinc levels were associated with greater sensitivity to sour taste (citric acid) (P = 0.015) only in the older groups (aged 70-90 y). There were no apparent associations between serum or erythrocyte zinc status and acuity for bitter (quinine) or sweet (sucrose) tastes irrespective of age. Conclusion: These results agree with those previously suggesting that age-related detriment in sensitivity for salt taste may be associated with depleted zinc.

To report the rational, design, recruitment, baseline characteristics and preliminary overview of volunteers in the ZENITH study. A multicentre prospective intervention study employing a randomised double-blind design. Clermont-Ferrand, Theix (France), Coleraine (Northern Ireland), Grenoble (France), Rome (Italy). Healthy men and women middle-aged (55–70 y) and older volunteers (70–87 y). At baseline (prior to zinc (Zn) supplementation), all volunteers underwent a full clinical examination, anthropometric measurements, health and lifestyle questionnaire, Mini Mental State Examination, Geriatric Depression Scale, and biochemistry profile. In total, 842 volunteers (378 men and 464 women) were invited to take part in the study. A total of 49% of these volunteers were excluded on the basis of inclusion/exclusion criteria. In total, 433 participants were admitted to the Zn supplementation for 6 months. During this period, about 10% of volunteers dropped out from the study. A total of 387 subjects (197 male and 190 female subjects) successfully completed the supplementation phase of the ZENITH study. The ZENITH study is supported by the European Commission ‘Quality of Life and Management of Living Resources’ Fifth Framework Programme, Contract No: QLK1-CT-2001-00168.