The effect of camelina oil on vascular function in essential hypertensive patients with metabolic syndrome: a randomized, placebo-controlled, double-blind study.

BACKGROUND: The effects of a dietary supplementation with the vegetable ω-3 α-linolenic acid (ALA) on cardiovascular homeostasis are unclear. In this context, it would be interesting to assess the effects of camelina oil. OBJECTIVE: This study aimed to assess the cardiovascular and metabolic effects of camelina oil in hypertensive patients with metabolic syndrome. METHODS: In a double-blind, placebo-controlled randomized study, treated essential hypertensive patients with metabolic syndrome received, during 6 mo, either cyclodextrin-complexed camelina oil containing ≈ 1.5 g ALA/d (n = 40) or an isocaloric placebo (n = 41), consisting of the same quantity of cyclodextrins and wheat starch. Anthropometric data, plasma lipids, glycemia, insulinemia, creatininemia, TBARs, high-sensitivity C-reactive protein, and n-3, n-6, and n-9 fatty acids in erythrocyte membranes were measured. Peripheral and central blood pressures, arterial stiffness, carotid intima-media thickness, and brachial artery endothelium-dependent flow-mediated dilatation (FMD) and endothelium-independent dilatation were assessed. RESULTS: Compared with placebo, camelina oil increased ALA (mean ± SD: 0 ± 0.04 compared with 0.08 ± 0.06%, P <0.001), its elongation product EPA (0 ± 0.5 compared with 0.16 ± 0.65%, P <0.05), and the n-9 gondoic acid (GA; 0 ± 0.04 compared with 0.08 ± 0.04%, P <0.001). No between-group difference was observed for cardiovascular parameters. However, changes in FMD were associated with the magnitude of changes in EPA (r = 0.26, P = 0.03). Compared with placebo, camelina oil increased fasting glycemia (-0.2 ± 0.6 compared with 0.3 ± 0.5 mmol/L, P <0.001) and HOMA-IR index (-0.8 ± 2.5 compared with 0.5 ± 0.9, P <0.01), without affecting plasma lipids, or inflammatory and oxidative stress markers. Changes in HOMA-IR index were correlated with the magnitude of changes in GA (r = 0.32, P <0.01). Nutritional intake remained similar between groups. CONCLUSION: ALA supplementation with camelina oil did not improve vascular function but adversely affected glucose metabolism in hypertensive patients with metabolic syndrome. Whether this adverse effect on insulin sensitivity is related to GA enrichment, remains to be elucidated.

Rapeseed oil fortified with micronutrients improves cognitive alterations associated with metabolic syndrome.

Metabolic syndrome represents a major risk factor for severe comorbidities such as cardiovascular diseases or diabetes. It is also associated with an increased prevalence of emotional and cognitive alterations that in turn aggravate the disease and related outcomes. Identifying therapeutic strategies able to improve those alterations is therefore a major socioeconomical and public health challenge. We previously reported that both hippocampal inflammatory processes and neuronal plasticity contribute to the development of emotional and cognitive alterations in db/db mice, an experimental model of metabolic syndrome that displays most of the classical features of the syndrome. In that context, nutritional interventions with known impact on those neurobiological processes appear as a promising alternative to limit the development of neurobiological comorbidities of metabolic syndrome. We therefore tested here whether n-3 polyunsaturated fatty acids (n-3 PUFAs) associated with a cocktail of antioxidants can protect against the development of behavioral alterations that accompany the metabolic syndrome. Thus, this study aimed: 1) to evaluate if a diet supplemented with the plant-derived n-3 PUFA α-linolenic acid (ALA) and antioxidants (provided by n-3 PUFAs-rich rapeseed oil fortified with a mix of naturally constituting antioxidant micronutrients, including coenzyme Q10, tocopherol, and the phenolic compound canolol) improved behavioral alterations in db/db mice, and 2) to decipher the biological mechanisms underlying this behavioral effect. Although the supplemented diet did not improve anxiety-like behavior and inflammatory abnormalities, it reversed hippocampus-dependent spatial memory deficits displayed by db/db mice in a water maze task. It concomitantly changed subunit composition of glutamatergic AMPA and NMDA receptors in the hippocampus that has been shown to modulate synaptic function related to spatial memory. These data suggest that changes in local neuronal plasticity may underlie cognitive improvements in db/db mice fed the supplemented diet. The current findings might therefore provide valuable data for introducing new nutritional strategies for the treatment of behavioral complications associated with MetS.

Vitamin D supplementation and muscle strength in pre-sarcopenic elderly Lebanese people: a randomized controlled trial.

Previous studies have shown that improving vitamin D status among the elderly may lead to an improvement in muscle mass and muscle strength. In our study, vitamin D supplementation showed significant improvements in vitamin D concentrations as well as appendicular muscle mass in pre-sarcopenic older Lebanese people. However, we found no significant effect on muscle strength. INTRODUCTION: Improving vitamin D status might improve muscle function and muscle mass that lead to sarcopenia in older subjects. The aim of this randomized, controlled, double-blind study was to examine the effect of vitamin D supplementation on handgrip strength and appendicular skeletal muscle mass in pre-sarcopenic older Lebanese subjects. We also examined whether this effect differs in normal vs. obese subjects. METHODS: Participants (n = 128; 62 men and 66 women) deficient in vitamin D (25(OH)D = 12.92 ± 4.3 ng/ml) were recruited from Saint Charles Hospital, Beirut, Lebanon. The participants were given a supplement of 10,000 IU of cholecalciferol (vitamin D group; n = 64) to be taken three times a week or a placebo tablet (placebo group; n = 64) for 6 months. One hundred fifteen subjects completed the study: 59 had normal weight, while 56 were obese. Strength and functional assessment and biochemical analysis were performed at the start and after 6 months. RESULTS: Compared to placebo, the vitamin D supplemented group showed significant improvements in appendicular skeletal muscle mass (ASMM) (P < 0.001) but not in handgrip strength (P = 0.2901). ANCOVA for ASMM adjusting for obesity and including the interaction between obesity and vitamin D showed a significant interaction. The increase in ASMM with vitamin D in normal-weight subjects was higher than that of obese subjects (B = 35.09 vs. B = 2.19). CONCLUSION: Treatment with vitamin D showed beneficial effects on appendicular muscle mass in pre-sarcopenic older Lebanese men and women. However, it had no effect on muscle strength relative to placebo. This trial was registered at isrctn.org as ISRCTN16665940.

Rapeseed oil fortified with micronutrients can reduce glucose intolerance during a high fat challenge in rats.

BACKGROUND: Better choices of dietary lipid sources and substitution of refined by fortified oils could reduce the intake of saturated fatty acids (FA) and increase the intake of omega 3 FA concomitantly to healthy bioactive compounds. METHODS: The development of obesity and metabolic disturbances was explored in rats fed during 11 weeks with a high fat diet (HFD) in which the amount of saturated and polyunsaturated FA was respectively reduced and increased, using rapeseed oil as lipid source. This oil was used in a refined form (R) or fortified (10 fold increase in concentration) with endogenous micronutrients (coenzyme Q10 + tocopherol only (RF) only and also with canolol (RFC)). The effect of substituting palm by rapeseed oil was analysed using a student t test, oil fortification was analysed using ANOVA statistical test. RESULTS: Despite a similar weight gain, diets R, RF and RFC improved glucose tolerance (+ 10%) of the rats compared to a standard HFD with palm and sunflower oils as lipid source. Plasma glucose was lowered in RF and RFC groups (- 15 and 23% respectively), although triacylglycerol level was only reduced in group RFC (- 33%) compared to R. The fortification with canolol promoted the activation of Akt and AMP-activated protein kinase (AMPK) in skeletal muscle and subcutaneous adipose tissue respectively. Canolol supplementation also led to reduce p38 MAPK activation in skeletal muscle. CONCLUSIONS: This study suggests that the presence of endogenous micronutrients in rapeseed oil promotes cellular adaptations to reverse glucose intolerance and improve the metabolism of insulin sensitive tissues.

Dietary canolol protects the heart against the deleterious effects induced by the association of rapeseed oil, vitamin E and coenzyme Q10 in the context of a high-fat diet.

BACKGROUND: Obesity progressively leads to cardiac failure. Omega-3 polyunsaturated fatty acids (PUFA) have been shown to have cardio-protective effects in numerous pathological situations. It is not known whether rapeseed oil, which contains α-linolenic acid (ALA), has a similar protective effect. Omega-3 PUFAs are sensitive to attack by reactive oxygen species (ROS), and lipid peroxidation products could damage cardiac cells. We thus tested whether dietary refined rapeseed oil (RSO) associated with or without different antioxidants (vitamin E, coenzyme Q10 and canolol) is cardio-protective in a situation of abdominal obesity. METHODS: Sixty male Wistar rats were subdivided into 5 groups. Each group was fed a specific diet for 11 weeks: a low-fat diet (3% of lipids, C diet) with compositionally-balanced PUFAs; a high-fat diet rich in palm oil (30% of lipids, PS diet); the PS diet in which 40% of lipids were replaced by RSO (R diet); the R diet supplemented with coenzyme Q10 (CoQ10) and vitamin E (RTC diet); and the RTC diet supplemented with canolol (RTCC diet). At the end of the diet period, the rats were sacrificed and the heart was collected and immediately frozen. Fatty acid composition of cardiac phospholipids was then determined. Several features of cardiac function (fibrosis, inflammation, oxidative stress, apoptosis, metabolism, mitochondrial biogenesis) were also estimated. RESULTS: Abdominal obesity reduced cardiac oxidative stress and apoptosis rate by increasing the proportion of arachidonic acid (AA) in membrane phospholipids. Dietary RSO had the same effect, though it normalized the proportion of AA. Adding vitamin E and CoQ10 in the RSO-rich high fat diet had a deleterious effect, increasing fibrosis by increasing angiotensin-2 receptor-1b (Ag2R-1b) mRNA expression. Overexpression of these receptors triggers coronary vasoconstriction, which probably induced ischemia. Canolol supplementation counteracted this deleterious effect by reducing coronary vasoconstriction. CONCLUSION: Canolol was found to counteract the fibrotic effects of vitamin E + CoQ10 on cardiac fibrosis in the context of a high-fat diet enriched with RSO. This effect occurred through a restoration of cardiac Ag2R-1b mRNA expression and decreased ischemia.

Is there a linear relationship between the dose of ruminant trans-fatty acids and cardiovascular risk markers in healthy subjects: results from a systematic review and meta-regression of randomised clinical trials.

The effects of ruminant (R) trans-fatty acids (TFA) on the risk of CVD are still under debate. It could be argued that the lack of the effect of R-TFA may be the result of the small amount of their intake. Taking into consideration the growing available data from intervention studies, we carried out a systematic review and meta-regression to assess the impact of R-TFA intake levels on changes in the total cholesterol: HDL-cholesterol (TC:HDL-C) ratio. A systematic review of the literature was conducted and thirteen randomised clinical trials were included, yielding a total of twenty-three independent experimental groups of subjects. A univariate random-effects meta-regression approach was used to quantify the relationship between the dose of R-TFA and changes in the TC:HDL-C ratio. To consider several potential modifiers such as subject and dietary characteristics, a multivariate regression analysis was performed. We found no relationship between R-TFA intake levels of up to 4.19% of daily energy intake (EI) and changes in cardiovascular risk factors such as TC:HDL-C and LDL-cholesterol (LDL-C):HDL-C ratios. In addition, a multivariate regression analysis that included other dietary variables, as well as subject baseline characteristics, confirmed that doses of R-TFA did not significantly influence the changes in the lipid ratio. Our findings showed that doses of R-TFA did not influence the changes in the ratios of plasma TC:HDL-C and LDL-C:HDL-C. These data suggest that TFA from natural sources, at least at the current levels of intake and up to 4.19% EI, have no adverse effects on these key CVD risk markers in healthy people.

Muscle ectopic fat deposition contributes to anabolic resistance in obese sarcopenic old rats through eIF2α activation.

Obesity and aging are characterized by decreased insulin sensitivity (IS) and muscle protein synthesis. Intramuscular ceramide accumulation has been implicated in insulin resistance during obesity. We aimed to measure IS, muscle ceramide level, protein synthesis, and activation of intracellular signaling pathways involved in translation initiation in male Wistar young (YR, 6-month) and old (OR, 25-month) rats receiving a low- (LFD) or a high-fat diet (HFD) for 10 weeks. A corresponding cellular approach using C2C12 myotubes treated with palmitate to induce intracellular ceramide deposition was taken. A decreased ability of adipose tissue to store lipids together with a reduced adipocyte diameter and a development of fibrosis were observed in OR after the HFD. Consequently, OR fed the HFD were insulin resistant, showed a strong increase in intramuscular ceramide level and a decrease in muscle protein synthesis associated with increased eIF2α phosphorylation. The accumulation of intramuscular lipids placed a lipid burden on mitochondria and created a disconnect between metabolic and regulating pathways in skeletal muscles of OR. In C2C12 cells, palmitate-induced ceramide accumulation was associated with a decreased protein synthesis together with upregulated eIF2α phosphorylation. In conclusion, a reduced ability to expand adipose tissues was found in OR, reflecting a lower lipid buffering capacity. Muscle mitochondrial activity was affected in OR conferring a reduced ability to oxidize fatty acids entering the muscle cell. Hence, OR were more prone to ectopic muscle lipid accumulation than YR, leading to decreased muscle protein anabolism. This metabolic change is a potential therapeutic target to counter sarcopenic obesity.

Combined food intake and exercise unmask different hormonal responses in lean and obese children.

Our purpose was to investigate the effect of obesity in prepubertal children on the hormonal response to exercise performed under different conditions of nutrient availability. Prepubertal obese (age, 10.3 ± 1.8 years; %body fat, 36.1 ± 6.1; n = 9) and lean (age, 9.2 ± 1.6 years; %body fat, 22.2 ± 4.1; n = 7) children completed 2 experimental sessions in which they performed a 30 min of cycling exercise at 50% of their maximal aerobic power either 1 h (T1h) or 3 h (T3h) after a standardized breakfast. Plasma insulin-like growth factor 1 (IGF-1), IGF binding protein 1 (IGFBP-1), and IGFBP-3 levels were assessed at baseline and after exercise. Urine was collected during the sessions, and catecholamine and glucocorticoid excretions were analyzed. A significant time effect was observed for IGFBP-1; postexercise levels decreased in lean and obese children (p ≤ 0.001). IGF-1 and IGFBP-3 were not affected by obesity or food intake combined with exercise. In lean children, urinary excretion rates of epinephrine, norepinephrine, cortisol, and cortisone were significantly higher during the sessions than during the overnight resting period; in obese children, only epinephrine in T1h was significantly increased (p ≤ 0.05 for all). Our study indicates that the activity of the hypothalamic-pituitary-adrenal axis and sympathetic adrenal medullary axis was similar in lean and obese children, based on measurement under resting conditions, but response to exercise performed in postprandial conditions was altered in obese children for both axes. In addition, exercise in the postprandial state elicited a decrease in IGFBP-1 plasma levels, whereas IGF-1 and IGFBP-3 levels were not significantly altered.

Plant-based foods as a source of lipotropes for human nutrition: a survey of in vivo studies.

Increased consumption of plant products is associated with lower chronic disease prevalence. This is attributed to the great diversity of healthy phytochemicals present in these foods. The most investigated physiological effects have been their antioxidant, anti-carcinogenic, hypolipidemic, and hypoglycemic properties. Although less studied in humans, some compounds were very early on shown to be lipotropic in animals, i.e., the capacity to hasten the removal of fat from liver and/or reduce hepatic lipid synthesis or deposits by mainly increasing phospholipid synthesis via the transmethylation pathway for triglyceride-rich lipoprotein exportation from the liver and enhanced fatty acid ß-oxidation and/or down- and up-regulation of genes involved in lipogenic and fatty acid oxidation enzyme synthesis, respectively. The main plant lipotropes are choline, betaine, myo-inositol, methionine, and carnitine. Magnesium, niacin, pantothenate, and folates also indirectly support the overall lipotropic effect. The exhaustive review of rat studies investigating phytochemical effect on hepatic lipid metabolism suggests that some fatty acids, acetic acid, melatonin, phytic acid, some fiber compounds, oligofructose, resistant starch, some phenolic acids, flavonoids, lignans, stilbenes, curcumin, saponins, coumarin, some plant extracts, and some solid foods may be lipotropic. However, this remains to be confirmed in humans, for whom intervention studies are practically non-existent. Supplemental materials are available for this article. Go to the publisher's online edition of Critical Reviews in Food Science and Nutrition® to view the free supplemental file.

Optimized rapeseed oil enriched with healthy micronutrients: a relevant nutritional approach to prevent cardiovascular diseases. Results of the Optim'Oils randomized intervention trial.

Rapeseeds are naturally rich in cardioprotective micronutrients but refining leads to substantial losses or the production of undesirable compounds. The Optim'Oils European project proposed innovative refining conditions to produce an optimized rapeseed oil enriched in micronutrients and low in trans linolenic acid. We aimed to investigate cardioprotective properties of this Optimized oil. In a randomized, double-blind, controlled, cross-over study, 59 healthy normolipidaemic men consumed either Optimized or Standard rapeseed oils (20 g/d) and margarines (22 g/d) for 3 weeks. The Optimized oil reduced the trans FA concentration (p=0.009) and increased the contents of alpha-tocopherol (p=0.022) and coenzyme Q10 (p<0.001) in comparison with the Standard oil. Over the 3-week trial, Total-/HDL-cholesterol and LDL-/HDL-cholesterol were increased by 4% (p<0.05) with the Standard oil consumption whereas none of them rose with the Optimized rapeseed oil which increased the HDL-cholesterol and ApoA1 plasma content (+2%, NS and +3%, p<0.05 respectively). The effects observed on the plasma HDL-cholesterol levels (p=0.059), the Total-/HDL-cholesterol ratio (p=0.092), and on the ApoA1 concentrations (p=0.060) suggest an improvement of the cholesterol profile with the Optimized rapeseed oil. Finally, the Optimized oil reduced the plasma content of LDLox (-6%, NS), this effect being significantly different from the Standard oil (p=0.050). In conclusion, reasonable intake of an Optimized rapeseed oil resulting from innovative refining processes and enriched in cardioprotective micronutrients represent a relevant nutritional approach to prevent the risk of cardiovascular diseases by improving the cholesterol profile and reducing LDL oxidation.

TNFα gene knockout differentially affects lipid deposition in liver and skeletal muscle of high-fat-diet mice.

AIMS/HYPOTHESIS: Inflammation and ectopic lipid deposition contribute to obesity-related insulin resistance (IR). Studies have shown that deficiency of the proinflammatory cytokine tumor necrosis factor-α (TNFα) protects against the IR induced by a high-fat diet (HFD). We aimed to evaluate the relationship between HFD-related inflammation and lipid deposition in skeletal muscle and liver. EXPERIMENTAL DESIGN: Wild-type (WT) and TNFα-deficient (TNFα-KO) mice were subjected to an HFD for 12 weeks. A glucose tolerance test was performed to evaluate IR. Inflammatory status was assessed by measuring plasma and tissue transcript levels of cytokines. Lipid intermediate concentrations were measured in plasma, muscle and liver. The expression of genes involved in fatty acid transport, synthesis and oxidation was analyzed in adipose tissue, muscle and liver. RESULTS: HFD induced a higher body weight gain in TNFα-KO mice than in WT mice. The weight of epididymal and abdominal adipose tissues was twofold lower in WT mice than in TNFα-KO mice, whereas liver weight was significantly heavier in WT mice. IR, systemic and adipose tissue inflammation, and plasma nonesterified fatty acid levels were reduced in TNFα-KO mice fed an HFD. TNFα deficiency improved fatty acid metabolism and had a protective effect against lipid deposition, inflammation and fibrosis associated with HFD in liver but had no impact on these markers in muscle. CONCLUSIONS: Our data suggest that in an HFD context, TNFα deficiency reduced hepatic lipid accumulation through two mechanisms: an increase in adipose tissue storage capacity and a decrease in fatty acid uptake and synthesis in the liver.

Increasing intake of long-chain n-3 PUFA enhances lipoperoxidation and modulates hepatic gene expression in a dose-dependent manner.

Long-chain (LC) n-3 PUFA have a broad range of biological properties that can be achieved at the gene expression level. This has been well described in liver, where LC n-3 PUFA modulate the expression of genes related to lipid metabolism. However, the complexity of biological pathway modulations and the nature of bioactive molecules are still under investigation. The present study aimed to investigate the dose-response effects of LC n-3 PUFA on the production of peroxidised metabolites, as potential bioactive molecules, and on global gene expression in liver. Hypercholesterolaemic rabbits received by daily oral administration (7 weeks) either oleic acid-rich oil or a mixture of oils providing 0.1, 0.5 or 1 % (groups 1, 2 and 3 respectively) of energy as DHA. Levels of specific peroxidised metabolites, namely 4-hydroxyhexenal (4-HHE)-protein adducts, issued from LC n-3 PUFA were measured by GC/MS/MS in liver in parallel to transcription profiling. The intake of LC n-3 PUFA increased, in a dose-dependent manner, the hepatic production of 4-HHE. At the highest dose, LC n-3 PUFA provoked an accumulation of TAG in liver, which can be directly linked to increased mRNA levels of lipoprotein hepatic receptors (LDL-receptor and VLDL-receptor). In groups 1 and 2, the mRNA levels of microsomal TAG transfer protein decreased, suggesting a possible new mechanism to reduce VLDL secretion. These modulations of genes related to lipoprotein metabolism were independent of PPARα signalling but were probably linked to the activation of the farnesol X receptor pathway by LC n-3 PUFA and/or their metabolites such as HHE.

Borage and fish oils lifelong supplementation decreases inflammation and improves bone health in a murine model of senile osteoporosis.

Fats are prevalent in western diets; they have known deleterious effects on muscle insulin resistance and may contribute to bone loss. However, relationships between fatty acids and locomotor system dysfunctions in elderly population remain controversial. The aim of this study was to analyze the impact of fatty acid quality on the age related evolution of the locomotor system and to understand which aging mechanisms are involved. In order to analyze age related complications, the SAMP8 mouse strain was chosen as a progeria model as compared to the SAMR1 control strain. Then, two months old mice were divided in different groups and subjected to the following diets : (1) standard "growth" diet - (2) "sunflower" diet (high ω6/ω3 ratio) - (3) "borage" diet (high γ-linolenic acid) - (4) "fish" diet (high in long chain ω3). Mice were fed ad libitum through the whole protocol. At 12 months old, the mice were sacrificed and tissues were harvested for bone studies, fat and muscle mass measures, inflammation parameters and bone cell marker expression. We demonstrated for the first time that borage and fish diets restored inflammation and bone parameters using an original model of senile osteoporosis that mimics clinical features of aging in humans. Therefore, our study strongly encourages nutritional approaches as relevant and promising strategies for preventing aged-related locomotor dysfunctions.

Thermal and refining processes, not fermentation, tend to reduce lipotropic capacity of plant-based foods.

Plant-based foods (PBF) are relevant and diversified sources of lipotropes, which are compounds preventing excess hepatic fat deposits. In a first study, we defined the lipotropic capacity (LC, %) of raw PBF as the means of 8 lipotrope densities (LD, mg/100 kcal), each expressed relative to that of a reference food ranking the highest considering its mean 8 LD ranks (LC(raw asparagus)=100%) (A. Fardet, J.-F. Martin and J. M. Chardigny, J. Food Comp. Anal., 2011, DOI: 10.1016/j.jfca.2011.1003.1013). We showed that vegetables appeared as the best source of lipotropes on a 100 kcal-basis compared to legumes, cereals, fruits and nuts. The main objective of this second study was to quantify the effect of processing on LD and LC of raw PBF based on lipotrope contents collected in a USDA (United State Department of Agriculture) database and the literature, i.e. betaine, choline, myo-inositol, methionine, magnesium, niacin, pantothenic acid and folate contents. Choline and betaine densities were not significantly affected by processing while methionine and lipotropic micronutrient densities were significantly decreased, especially for magnesium, pantothenate and folates. Myo-inositol density decreases were insignificant due to lower product number resulting from limited literature data. Lipotropic micronutrient densities were more affected by processing than other densities. Fermentations increased betaine (median change of +32%) and choline (+34%) densities. Canning and boiling vegetables increased choline densities (+26%). Globally, processing significantly reduced LC by ∼20%, fermentations being less drastic (median change of -5%) than refining (-33%) and thermal treatments (-16%). More specifically, canning increased LC of beetroot (536 vs 390%) and common bean (40 vs 36%) as fermentation towards LC grape (14 vs 7% for wine). Results were then mainly discussed based on percentages of lipotrope content changes on a dry-weight basis. Results of this study also showed that the LC is quite a relevant index to estimate effect of processing on lipotropic potential of PBF.

Laparoscopic implantation of neural electrodes on pelvic nerves: an experimental study on the obturator nerve in a chronic minipig model.

BACKGROUND: Laparoscopic exposure of pelvic nerves has opened a new area in the field of neuromodulation. However, electrode design and material deterioration remain issues that limit clinical application. The objective of this study was to evaluate experimentally the laparoscopic implantation of different types of neural electrodes in order to achieve functional and selective electrical stimulation of pelvic nerves. METHODS: This was a prospective comparative study of the laparoscopic implantation and tolerance and efficacy of three monopolar cuff electrodes implanted on the obturator nerve in ten Göttingen minipigs (18-20 months old; 14.5-24 kg body weight). Animals were allocated to two groups. A 3-mm-diameter laparoscopic instrument was used during dissection of paravesical fossa and obturator nerve on both sides in order to minimize nerve damage. In all animals, a "split-cylinder" cuff electrode was implanted around the left obturator nerve. On the right side, a "lasso" cuff electrode was implanted in the first group and a "closed-cylinder" cuff was implanted in the second group. Electrical stimulation (0-5 V, 20 Hz) was performed for implanted electrodes on days 0, 7, 15, 30, 45, 60, and 90. Current intensity thresholds were identified by palpation of muscle contraction. Strength developed according to stimulation level and was measured using weight transducers. RESULTS: All procedures were performed by laparoscopy. Mean operative times differed significantly among groups, the shortest being for split-cylinder electrodes (P = 0.0002). No electrical spread phenomena were observed. Initial thresholds were below 1.5 V (range = 0.5-1.3); however, a significant rise was observed, with time to a maximum of 2.7 V (P < 0.0001). Only split-cylinder electrodes remained functional after 3 months. The mean value of maximum strength remained stable during the study period (P = 0.21, NS). CONCLUSIONS: The laparoscopic approach to implanting neuroprostheses seems to be very attractive. Furthermore, this approach could allow highly selective nerve stimulation to be achieved using simpler devices such as split-cylinder monopolar electrodes.

Effect of time interval between food intake and exercise on substrate oxidation during exercise in obese and lean children.

BACKGROUND & AIMS: Exercise induces adaptations in fat metabolism favourable to the treatment of obesity. However, time interval between meal and exercise alters substrate bioavailability and oxidation during exercise. The aim of this study was therefore to investigate the effect of time interval between food intake and exercise on substrate oxidation rates in obese and lean children. METHODS: The metabolic responses to exercise of nine obese children (10.3 ± 1.8 years; %body fat: 36.1 ± 6.1) and seven lean children (9.2 ± 1.6 years; %body fat: 22.2 ± 4.1) were compared 1 h (time interval 1, TI1) and 3 h (TI3) after a standardized breakfast. RESULTS: Despite significantly lower plasma glucose and insulin concentrations and large effect size suggesting a higher plasma FFA availability (lean, 1.43, obese 0.98), fat oxidation was not significantly increased in TI3 compared to TI1 in both lean and obese children. Fat oxidation contributed marginally to energy expenditure during exercise (<20%) in both conditions and groups but was moderately increased during TI3 compared to TI1 in lean children (effect size: 0.54). CONCLUSIONS: The low contribution of fat oxidation to energy expenditure during exercise in obese and lean children fed 3 h before exercise questions the efficacy of moderate intensity exercise to favourably affect fat balance.

Oleate-enriched diet improves insulin sensitivity and restores muscle protein synthesis in old rats.

BACKGROUND & AIMS: Age-related inflammation and insulin resistance (IR) have been implicated in the inability of old muscles to properly respond to anabolic stimuli such as amino acids (AA) or insulin. Since fatty acids can modulate inflammation and IR in muscle cells, we investigated the effect of palmitate-enriched diet and oleate-enriched diet on inflammation, IR and muscle protein synthesis (MPS) rate in old rats. METHODS: Twenty-four 25-month-old rats were fed either a control diet (OC), an oleate-enriched diet (HFO) or a palmitate-enriched diet (HFP) for 16 weeks. MPS using labeled amino acids and mTOR activation were assessed after AA and insulin anabolic stimulation to mimic postprandial state. RESULTS: IR and systemic and adipose tissue inflammation (TNFα and IL1ß) were improved in the HFO group. Muscle genes controlling mitochondrial ß-oxidation (PPARs, MCAD and CPT-1b) were up-regulated in the HFO group. AA and insulin-stimulated MPS in the HFO group only, and this stimulation was related to activation of the Akt/mTOR pathway. CONCLUSIONS: The age-related MPS response to anabolic signals was improved in rats fed an oleate-enriched diet. This effect was related to activation of muscle oxidative pathways, lower IR, and a decrease in inflammation.

Ruminant and industrial sources of trans-fat and cardiovascular and diabetic diseases.

The various positional isomers of oleic acid (18 : 1Δ9c or 9c-18 : 1) may have distinct biological effects. Detrimental effects of consumption of industrial trans-fatty acids (TFA) (elaidic acid; 18 : 1Δ9t) from partially hydrogenated vegetable oils on CVD risk factors are well documented. In addition, epidemiological data suggest that chronic consumption of industrial sources of TFA could alter insulin sensitivity and predispose for type 2 diabetes. However, intervention studies on this issue have remained inconclusive. Moreover, very little information is available on the effect of natural sources of TFA (vaccenic acid; 18 : 1Δ11t) coming from dairy products and ruminant meat on the development of CVD and type 2 diabetes. The review focuses on the impact of the consumption of ruminant TFA in relation to cardiovascular risk factors, inflammation and type 2 diabetes.

Effects of ruminant trans fatty acids on cardiovascular disease and cancer: a comprehensive review of epidemiological, clinical, and mechanistic studies.

There are 2 predominant sources of dietary trans fatty acids (TFA) in the food supply, those formed during the industrial partial hydrogenation of vegetable oils (iTFA) and those formed by biohydrogenation in ruminants (rTFA), including vaccenic acid (VA) and the naturally occurring isomer of conjugated linoleic acid, cis-9, trans-11 CLA (c9,t11-CLA). The objective of this review is to evaluate the evidence base from epidemiological and clinical studies to determine whether intake of rTFA isomers, specifically VA and c9,t11-CLA, differentially affects risk of cardiovascular disease (CVD) and cancer compared with iTFA. In addition, animal and cell culture studies are reviewed to explore potential pro- and antiatherogenic mechanisms of VA and c9,t11-CLA. Some epidemiological studies suggest that a positive association with coronary heart disease risk exists between only iTFA isomers and not rTFA isomers. Small clinical studies have been conducted to establish cause-and-effect relationships between these different sources of TFA and biomarkers or risk factors of CVD with inconclusive results. The lack of detection of treatment effects reported in some studies may be due to insufficient statistical power. Many studies have used doses of rTFA that are not realistically attainable via diet; thus, further clinical studies are warranted. Associations between iTFA intake and cancer have been inconsistent, and associations between rTFA intake and cancer have not been well studied. Clinical studies have not been conducted investigating the cause-and-effect relationship between iTFA and rTFA intake and risk for cancers. Further research is needed to determine the health effects of VA and c9,t11-CLA in humans.

Comparison of postprandial oleic acid, 9c,11t CLA and 10t,12c CLA oxidation in healthy moderately overweight subjects.

Few studies report the individual effect of 9c,11t- and 10t,12c-CLA on human energy metabolism. We compared the postprandial oxidative metabolism of 9c,11t- and 10t,12c-CLA and oleic acid (9c-18:1) in 22 healthy moderately overweight volunteers. After 24 weeks supplementation with 9c,11t-, 10t,12c-CLA or 9c-18:1 (3 g/day), subjects consumed a single oral bolus of the appropriate [1-(13)C]-labeled fatty acid. 8 h post-dose, cumulative oxidation was similar for 9c-18:1 and 10t,12c (P = 0.66), but significantly higher for 9c,11t (P < 0.01).