Fish oil minimises feed intake and improves insulin sensitivity in Zucker fa/fa rats.

Long-chain n-3 PUFA (LC n-3 PUFA) prevent, in rodents, insulin resistance (IR) induced by a high-fat and/or fructose diet but not IR induced by glucocorticoids. In humans, contrasting effects have also been reported. We investigated their effects on insulin sensitivity, feed intake (FI) and body weight gain in genetically insulin resistant male obese (fa/fa) Zucker (ZO) rats during the development of obesity. ZO rats were fed a diet supplemented with 7 % fish oil (FO) + 1 % corn oil (CO) (wt/wt) (ZOFO), while the control group was fed a diet containing 8 % fat from CO (wt/wt) (ZOCO). Male lean Zucker (ZL) rats fed either FO (ZLFO) or CO (ZLCO) diet were used as controls. FO was a marine-derived TAG oil containing EPA 90 mg/g + DHA 430 mg/g. During an oral glucose tolerance test, glucose tolerance remained unaltered by FO while insulin response was reduced in ZOFO only. Liver insulin sensitivity (euglycaemic-hyperinsulinaemic clamp + 2 deoxyglucose) was improved in ZOFO rats, linked to changes in phosphoenolpyruvate carboxykinase expression, activity and glucose-6-phosphatase activity. FI in response to intra-carotid insulin/glucose infusion was decreased similarly in ZOFO and ZOCO. Hypothalamic ceramides levels were lower in ZOFO than in ZOCO. Our study demonstrates that LC n-3 PUFA can minimise weight gain, possibly by alleviating hypothalamic lipotoxicity, and liver IR in genetically obese Zucker rats.

Long-chain n-3 PUFA given before and throughout gestation and lactation in rats prevent high-fat diet-induced insulin resistance in male offspring in a tissue-specific manner.

This study investigated whether long-chain n-3 PUFA (LC n-3 PUFA) given to pregnant rats fed a high-fat (HF) diet may prevent fetal programming in male offspring at adulthood. Six weeks before mating, and throughout gestation and lactation, female nulliparous Sprague-Dawley rats were given a chow (C) diet, HF (60·6 % fat from maize, rapeseed oils and lard) or HF in which one-third of fat was replaced by fish oil (HF n-3). At weaning, the three offspring groups were randomly separated in two groups fed C diet, or HF without LC n-3 PUFA, for 7 weeks until adulthood. Glucose tolerance and insulin sensitivity were assessed by an oral glucose tolerance test both at weaning and at adulthood. Insulin signalling was determined in liver, muscle and adipose tissue by quantification of the phosphorylation of Akt on Ser 473 at adulthood. At weaning, as at adulthood, offspring from HF-fed dams were obese and displayed glucose intolerance (GI) and insulin resistance (IR), but not those from HFn-3 fed dams. Following the post-weaning C diet, phosphorylation of Akt was strongly reduced in all tissues of offspring from HF dams, but to a lesser extent in liver and muscle of offspring from HFn-3 dams. However, it was abolished in all tissues of all offspring groups fed the HF post-weaning diet. Thus, LC n-3 PUFA introduced in a HF in dams partially prevented the transmission of GI and IR in adult offspring even though they were fed without LC n-3 PUFA from weaning.

[Definition, epidemiology and prognosis of undernutrition in adults]. / Définition, épidémiologie et pronostic de la dénutrition chez l'adulte.

DEFINITION, EPIDEMIOLOGY AND PROGNOSIS OF UNDERNUTRITION IN ADULTS Undernutrition is a pernicious and very frequent disease, particularly in hospitals (30 to 40% of adults) where it tends to worsen during the stay. The Covid-19 epidemic has further increased its prevalence. Its pernicious nature is that it is often considered as a symptom accompanying a pre-existing acute or chronic illness and not a disease in its own right. Even in 2022, in addition to the lack of prevention in at-risk populations, it very often remains undetected and/or insufficiently treated. However, it is accompanied by excess mortality and an increased risk of multiple complications: poorer healing, more frequent infections (particularly nosocomial), reduced immunity, increased prevalence of pressure sores, fistula in surgery, poorer quality of life, loss of autonomy, increased duration of artificial ventilation, and more difficult recovery from a pathology, particularly in the elderly. To this must be added an additional cost of care for one given disease or a group of given diseases. Its early diagnosis and management have proven to be effective: reduction of mortality, comorbidities and societal costs.

DÉFINITION, ÉPIDÉMIOLOGIE ET PRONOSTIC DE LA DÉNUTRITION CHEZ L'ADULTE La dénutrition est une maladie pernicieuse et très fréquente, en particulier à l'hôpital (30 à 40 % des adultes), où elle tend à s'aggraver pendant le séjour. L'épidémie de Covid-19 a encore augmenté sa prévalence. Sa nature pernicieuse tient au fait qu'elle est souvent considérée comme un symptôme accompagnant une maladie aiguë ou chronique préexistante et non comme une pathologie à part entière. Même en 2022, outre le défaut de prévention dans les populations à risque, elle reste très souvent non détectée et/ou insuffisamment traitée. Or elle s'accompagne d'une surmortalité et d'un risque accru de complications multiples : moins bonne cicatrisation, infections (notamment nosocomiales) plus fréquentes, baisse de l'immunité, accroissement de la prévalence des escarres, lâchage de suture en chirurgie, altération de la qualité de vie, perte d'autonomie, durée de ventilation artificielle accrue, récupération d'une pathologie plus difficile, en particulier chez le sujet âgé. Il faut ajouter à cela un surcoût de la prise en charge pour une maladie ou un groupe de pathologies données. Son diagnostic et sa prise en charge précoces ont fait la preuve de leur efficacité : diminution de la mortalité, des comorbidités et du coût sociétal.

French recommendations on the prevention and treatment of osteoporosis secondary to bariatric surgery.

INTRODUCTION: This article presents the initial recommendations of the Groupe de Recherche et d'Information sur les Ostéoporoses (Osteoporosis Research and Information Group [GRIO]) and the Société Française de Rhumatologie (French Rheumatology Society [SFR]) on the prevention and treatment of osteoporosis secondary to bariatric surgery. METHODS: The recommendations were produced by a working group comprising 4 expert rheumatologists, 3 medically qualified nutritionists, 2 obesity surgeons, 1 physical activity specialist, and 1 patient-association representative. RESULTS: The following generally recommended measures apply to all patients with an indication for bariatric surgery or who have already undergone bariatric surgery: normalize calcium and protein intake, attain a 25(OH) vitamin D concentration of between 30 and 60ng/mL; prevent the risk of falls, and introduce a suitable regimen of physical activity. An initial assessment of fracture risk should be routinely performed - ideally before the first bariatric surgery procedure - (i) in the case of RYGB and biliopancreatic diversion, regardless of age, (ii) in patients at high risk of fracture, regardless of age, and (iii) in all menopausal women and all men ≥ 50 years old, regardless of the type of bariatric surgical procedure. The fracture risk assessment is based on a determination of osteoporosis risk factors and bone mineral density measurements. Anti-osteoporosis treatment - zoledronic acid as the first line of treatment - is indicated for menopausal women and men ≥ 50 years old with (i) a history of severe fracture, regardless of T-score, (ii) a history of non-severe fracture and a T-score ≤ -1, and (iii) no history of fracture and a T-score ≤ -2. CONCLUSIONS: There is an increased risk of fracture after bariatric surgery. Clinicians should focus their attention on patients at high fracture risk such as postmenopausal women and men older than 50 years. More research is necessary to direct and support guidelines.

Contrasted central effects of n-3 versus n-6 diets on brain functions in diet-induced obesity in minipigs.

INTRODUCTION: N3 polyunsaturated fatty acids (n-3 PUFAs) exert anti-inflammatory effects for the hypothalamus, but their extra-hypothalamic outcome lack documentation. We evaluated the central consequences of the substitution of saturated fatty acids with n-3 or n-6 PUFA in obesogenic diets. METHODS: Twenty-one miniature pigs were fed ad libitum obesogenic diets enriched in fat provided either as lard, fish oil (source for n-3 PUFAs), or sunflower oil (source for n-6 PUFAs) for ten weeks. The blood-brain barrier (BBB) permeability was quantified by CT perfusion. Central autonomic network was evaluated using heart rate variability, and PET 18FDG was performed to assess brain metabolism. RESULTS: BBB permeability was higher in lard group, but heart rate variability changed only in fish oil group. Brain connectivity analysis and voxel-based comparisons show regional differences between groups except for the cingulate cortex in fish oil vs. sunflower oil groups. DISCUSSION: : The minute changes in brain metabolism in obese pigs feed with fish oil compared with saturated fatty acids were sufficient to induce detrimental changes in heart rate variability. On the contrary, the BBB's decreased permeability in n-3 and n-6 PUFAs groups was protective against an obesity-driven damaged BBB.

Diagnosing undernutrition children and adults: new French criteria. Why, for what and for whom? A joint statement of the French National Authority for Health and French Federation of Nutrition.

The objective was to establish new diagnostic criteria for undernutrition for the French population, concordant for children aged <18 years and adults aged <70 years, easy to use by health professionals and applicable whatever the situation (in and outpatients). A multi-disciplinary working and a reading group were involved. The procedure was divided into four phases: (1) systematic review and synthesis of the literature; (2) writing of the initial version of the guidelines; (3) reading and (4) finalisation. The literature search included international guidelines, meta-analyses, systematic reviews and randomised control trials from January 2007 to 31 July 2018. A two-step approach was selected: diagnosing undernutrition and then grading its severity. For diagnosis at least one phenotypic criterion associated with at least one aetiologic criterion were required for both children and adults. Phenotypic criteria for children were weight loss, Body Mass Index (BMI) < International Obesity Task Force curve 18·5, weight stagnation, reduction of muscle mass/function; for adults: weight loss, BMI < 18·5 and reduction of muscle mass/function. Aetiological criteria for children and adults were reduction in dietary intake, reduced absorption and hypercatabolism. Phenotypic metrics were used in both children and adults for grading severity (moderate or severe). These new French recommendations integrate the proposals of recent international recommendations combining aetiologic with phenotypic criteria, but for the first time, they are concordant for children and adults. The WHO threshold of 18·5 for BMI was kept as phenotypic criteria because epidemiological data show an increased mortality for that threshold.

Mediterranean Diet and cardiovascular health: an historical perspective.

The first investigation of dietary intake in the Mediterranean region was undertaken at the initiative of the government of Greece in 1948. Plant foods (cereals, pulses, nuts, potatoes, vegetables and fruits) accounted for 61 % of total energy intake (TEI), animal foods (meat, eggs, fish and dairy products) for 7 % of TEI and olive oil was the main oil used. In 1950s, Ancel Keys undertook studies in USA, Italy, Spain, England, Japan, Australia and Canada leading him to hypothesise that a link could exist between diet, plasma cholesterol and CHD. Between 1958 and 1964, Keys and co-workers carried out the Seven Countries Study, which enrolled men aged 40-59 years in one of sixteen cohorts from seven countries (Finland, Greece, Italy, Yugoslavia, Japan, USA and Italy). After 15-, 25- and 50-year follow-up, a strong positive relation was observed between saturated fat intake and CHD mortality, and a negative one with Mediterranean Dietary Index. In 1975, Keys and his wife published a book entitled: 'How to eat well and stay well. The Mediterranean way', which popularised Mediterranean Diet (MedDiet). After 45-year follow-up, longevity without CHD death was 12·9 years higher in Crete than in Finland. Protecting effect of MedDiet towards CHD incidence and risk is now confirmed by Prevencion con Dieta Mediterranea study and by cohorts' studies gathered in several recent meta-analyses. MedDiet is sustainable and recognised by UNESCO as an intangible cultural heritage, which is the most beautiful homage that can be paid to Ancel Keys and all his co-workers.

Activation of chicken gamma-delta T lymphocytes by a purified ulvan extract.

Chicken γδ T lymphocytes are present in a variety of tissues such as blood, spleen and intestine. They constitute a major cytotoxic population. In chicken, Salmonella immunization as well as vaccination against Newcastle disease virus are accompanied by an increase of γδ T lymphocytes in peripheral blood, which may be activated, and thus represent a protective immune response. It has been published that activation of avian γδ T cells can occur in a MHC non-restricted manner. Ulvans are complex sulfated polysaccharides composed of disaccharide repetitions found in the cell walls of green algae belonging to the genus Ulva. We recently demonstrated that a purified ulvan extract activates chicken heterophils and monocytes in vivo through TLR2 and TLR4 receptors when given in drinking water. We demonstrate here, that the same extract given once in drinking water at 25 and 50 mg/l, results in increased membrane expression of Major Histocompatibility Complex class 2 as soon as day 2, as detected using flow cytometry. We conclude chicken γδ T lymphocytes to be activated, or at least primed, in vivo, with the extract. Further experiments are required to fully understand whether their activation or priming is the result of direct and/or indirect mechanisms.

Dietary fatty acids and CHD: from specific recommendations to dietary patterns.

Several countries have issued dietary recommendations about total and specific fatty acid (FA) intake for the prevention of CHD. For many years until today, controversies have existed especially about the deleterious effect or not of SFA, and the protective effect or not of n-3 PUFA, so that some authors have criticised these recommendations. There are many reasons for these controversies, including the different conclusions of prospective cohort studies compared with randomised clinical trials (RCT), and the contradictory conclusions of meta-analyses depending on the quality, number and type of studies included. The interrelationships between different FA in the diet make it difficult to analyse the specific effect of a particular class of FA on CHD. Furthermore, based on clinical practice and effectiveness of population-based prevention, it is very difficult at the individual level to assess in personal dietary intake the actual percentage and/or amount of SFA contained in each meal or consumed daily/weekly. In this critical narrative review, we try to answer the question of whether it would not be more relevant, in 2020, to promote dietary patterns, rather than FA intake recommendations. We critically analyse past and recent data on the association of FA with CHD, then propose that the Mediterranean diet and Japanese diet should be revitalised for Westerners and Asian populations, respectively. This does not exclude the usefulness of continuing research about effects of FA towards CHD, and accepting that what seems true today might be revised, at least partially tomorrow.

Are marine n-3 fatty acids protective towards insulin resistance? From cell to human.

Marine n-3 fatty acids improve most of the biochemical alterations associated with insulin resistance (IR). Experimental models of dietary-induced IR in rodents have shown their ability (often at a very high dose) to prevent IR, but with sometimes a tissue specific effect. However, in a high sucrose diet-induced IR rat model, they are unable to reverse IR once installed; in other rodent models (dexamethasone, Zucker rats), they are inefficacious perhaps because of the severity of IR. The very low incidence of type-2 diabetes (T2D) in Inuits in the 1960s, which largely increased over the following decades in parallel to the replacement of their traditional marine food for a western diet strongly suggests a protective effect of marine n-3 towards the risk of T2D; this was confirmed by reversal of its incidence in intervention studies reintroducing their traditional food. In healthy subjects and insulin-resistant non-diabetic patients, most trials and meta-analyses conclude to an insulin-sensitising effect and to a very probable preventive or alleviating effect towards IR. Concerning the risk of T2D, concordant data allow us to conclude the protective effect of marine n-3 in Asians while suspicion exists of an aggravation of risk in Westerners, but with the possibility that it could be explained by a high heterogeneity of studies performed in this population. Some longitudinal cohorts in US/European people showed no association or a decreased risk. Further studies using more homogeneous doses, sources of n-3 and assessment of insulin sensitivity methods are required to better delineate their effects in Westerners.

Weight Loss and Nutritional Outcomes 10 Years after Biliopancreatic Diversion with Duodenal Switch.

BACKGROUND: Biliopancreatic diversion with duodenal switch (BPD/DS) is the most effective bariatric surgical procedure, but major concerns exist about the nutritional consequences. OBJECTIVES: The study reported weight loss and nutritional outcomes of 80 patients with a follow-up of at least 10 years. SETTING: The follow-up was conducted at a university hospital as well as in a private practice institution in France. METHODS: Eighty patients operated on between February 2002 and May 2006 were reviewed. Weight outcomes were analyzed as well as complete biological status. Revisions were reported as well as the number of patients taking vitamin supplementation. RESULTS: A follow-up of 141 ± 16 months was available for 87.7% of the patients at least 10 years from surgery. Preoperative BMI decreased from 48.9 ± 7.3 to 31.2 ± 6.2 kg/m2 with an EWL of 73.4 ± 26.7% and a TWL of 35.9% ± 17.7%. Despite weight regain ≥10% of the weight loss in 61% of the cases, 78% of the patients maintained a BMI <35. Fourteen percent of the patients had a revision. Normal vitamin D levels were found in 35.4%. The overall PTH level was 91.9 ± 79.5 ng/mL, and 62% of the patients had hyperparathyroidism. Other deficiencies were less frequent but fat-soluble deficiencies as well as a PTH >100 ng/mL were significantly associated with the absence of vitamin supplementation. CONCLUSION: BPD/DS maintains a significant weight loss, but remains associated with side effects leading to revision and multiple vitamin deficiencies. The most severe deficiencies are related to the lack of supplementation compliance.

Laparoscopic sleeve gastrectomy versus laparoscopic mini gastric bypass: One year outcomes.

PURPOSE: Sleeve gastrectomy (LSG) and mini gastric bypass (LMGB) was considered as emerging procedures but are now considered for many authors as an alternative of the Roux-Y gastric bypass because of similar percentages of weight loss and better postoperative morbidity profiles. However, studies comparing LSG and LMGB are scarce. MATERIALS AND METHODS: From January 2010 to July 2014, 262 and 161 patients underwent LSG or LMGB in two centre of bariatric surgery, respectively. At one year, rate of follow-up was 88.4%. Main outcome was % of Total Weight Loss (%TWL) at one year. Propensity score matching and multivariable analyses were used to compensate for differences in some baseline characteristics. RESULTS: After matching LSG (N = 136) and LMGB (N = 136) groups did not differ for initial BMI (kg/m(2)) (43.4 ± 6.5 vs. 42.8 ± 5.0; P = 0.34), % of female patients (91.9% vs. 93.4%; P = 0.64), age (years) (41.2 ± 12.3 vs. 41.2 ± 11.3; P = 0.99) and diabetes (15.4% vs. 19.9%; P = 0.34). At one year, %TWL, change in BMI and rate of stenosis were higher for LMGB group, respectively: 38.2 ± 8.4 vs. 34.3 ± 8.4 (P < 0.0001); -16.5 ± 4.6 vs. -14.9 ± 4.4 (P = 0.005) and 16.9% vs. 0% (P < 0.0001). In multivariate analyses (ß coefficient), LMGB was a positive independent factor of %TWL (2.8; P = 0.008). CONCLUSION: LMGB seems to have better weight loss at one year compared to LSG with higher gastric complications. Further long term studies are needed.

Interaction of low dose of fish oil and glucocorticoids on insulin sensitivity and lipolysis in healthy humans: A randomized controlled study.

SCOPE: This study examined the interaction of fish oil (FO) with dexamethasone on glucose and lipid metabolisms in healthy subjects. METHODS AND RESULTS: The study included two consecutive parts. Part A (randomized) in 16 subjects studied the effects of dexamethasone (2 days, 2 mg/day) versus placebo (lactose), part B (two parallel subgroups of eight) studied the interaction of FO (3 wk, 840 mg/day of EPA + DHA) with dexamethasone. Insulin sensitivity of lipolysis (d5-glycerol infusion + microdialysis), endogenous glucose production, and muscle glucose uptake were assessed by a three-step hot insulin clamp and substrate oxidation by indirect calorimetry. Dexamethasone induced liver and peripheral insulin resistance, an increase in fat oxidation, and a decrease in suppression of plasma nonesterified fatty acids (NEFAs). FO amplified the effects of dexamethasone by increasing liver and muscle insulin resistance, by reducing suppression of plasma NEFAs and fat oxidation and by increasing adipose tissue (AT) lipolysis. CONCLUSION: FO, given at a moderate dose in healthy subjects prior to a very short-term (2 days) low dose of a synthetic glucocorticoid, worsened its deleterious effects on insulin sensitivity. The enhancing effect of FO on fat oxidation and AT lipolysis might be a protective effect toward an increase in fat mass.

Nonalcoholic fatty liver disease: Roles of the gut and the liver and metabolic modulation by some dietary factors and especially long-chain n-3 PUFA.

Nonalcoholic fatty liver disease (NAFLD), including nonalcoholic steatohepatitis (NASH), is the leading cause of chronic liver disease in Western countries. NASH increases the risk for fibrosis, cirrhosis, and hepatocellular carcinoma. The mechanisms underlying the steatosis to NASH transition remain incompletely understood despite recent progress in cellular and molecular aspects. Our primary aim is to analyze recent advances in understanding deviations in hepatic fat metabolism and the implication of gut physiology and microbiota in this transition. Our second aim is to gather experimental and clinical data on the capability of long-chain n-3 PUFA (LC n-3 PUFA), including docosahexaenoic (DHA) and eicosapentaenoic (EPA) acids to prevent or alleviate NAFLD. Our main conclusions are: (i) increasing data support a pivotal role for the gut toward NASH development; (ii) LC n-3 PUFA have often proven preventive or therapeutic effect toward NASH development in rodent models. In patients with NASH they appear to have no therapeutic effects, but they could have preventive effects, which require to define better the specific roles, modes of action, and doses of DHA and EPA.

Opportunities to enhance alternative sources of long-chain n-3 fatty acids within the diet.

Health benefits or advocated health benefits of long-chain (LC) n-3 PUFA are better known by medical doctors as well as by consumers, so that consumption increases. In addition, the development of aquaculture requires more fishmeal and fish oil. Humanisation of care of companion animals is also associated with addition of LC n-3 PUFA in pet foods. The risk of the increased demand for LC n-3 PUFA is the excess harvesting of natural sources, especially of marine origin (oily fishes, krill). In order to improve sustainability, alternative sources of LC n-3 PUFA have been developed. These alternative sources are: (a) terrestrial plants naturally or genetically enriched in stearidonic acid (SDA), which bypasses the first limiting step of (i.e. ∆6 desaturase) of the biosynthesis of LC n-3 PUFA; (b) single-cell oils rich in LC n-3 PUFA (microalgae, Escherichia coli) and krill. Currently, plants rich in SDA are expensive, metabolic engineering is unfavourably accepted by consumers in many countries, cultivation of microalgae is very expensive even though their ability (for some of them) to synthesise biofuels could induce a decrease in industrial costs, and Antarctic krill harvest must be restricted. Thus, it is difficult to predict their real development in the future.

Polyunsaturated fatty acids inhibit PI3K activity in a yeast-based model system.

The phosphatidylinositol 3-kinase (PI3K) pathway controls the regulation of cell growth, proliferation, migration and apoptosis. In many tumors, the PI3K gene is mutated or overexpressed, and/or the PI3K pathway is hyperactive. PI3K is therefore a potential pharmacological target for the development of anti-tumor drugs. Some polyunsaturated fatty acids (PUFA), when given in the diet, may lead to a decrease in PI3K activity. We used a yeast-based model to reconstitute the PI3K/PTEN/Akt pathway to study the effects of long-chain polyunsaturated n-3 fatty acids on PI3K, and found that various PUFA were able to alleviate toxicity induced by overexpression of PI3K. The various PUFA had no significant effect on the steady-state level of PI3K catalytic subunit proteins (p110alpha) in yeast. However, depletion of phosphatidylinositol 4,5-bisphosphate due to overexpression of the p110alpha subunit was significantly reduced by treating the yeast cells with the various PUFA. The inhibition of mammalian PI3K, expressed in an exogenous cellular context in yeast, is likely to be a direct effect of these PUFA on PI3K rather than on other mammalian endogenous or environmental factors. These results are particularly promising given the abundance of active PUFA in marine foodstuffs and especially fish oils.

Effects of n-3 fatty acids and acute exercise on endothelium-dependent vasorelaxation in healthy rat aorta.

The purpose of this study was to determine whether n-3 PUFA result in an effect on endothelial function that is in addition to that of acute exercise. For 4 weeks, male Sprague-Dawley rats were subjected to a diet based on n-3 PUFA or a standard diet. In each diet group, ten rats were submitted to an acute treadmill exercise while the remaining ten acted as sedentary controls. The running speed was progressively increased until the animals were exhausted. Endothelial function was then assessed by measuring isometric tension in rings of the thoracic aorta. In vessels precontracted with 0.1 microm-phenylephrine, responses to acetylcholine (ACh) were significantly improved following acute exercise in all diet groups. When PUFA supplementation was compared to the standard diet no significant difference was found in response to ACh, either at rest or after an acute exercise. Pretreatment of rings with Nomega-nitro-l-arginine methyl esther (50 microm) inhibited the ACh-mediated vasorelaxation in all groups. Response to 10 microm-nifedipine, an L-type Ca2+ channel antagonist, was similarly enhanced after acute exercise in both standard and PUFA diets. Furthermore, response to 0.01 microm-nifedipine was significantly higher after acute exercise only in the PUFA diet. In conclusion, in our 'healthy' rat model with 'normal' baseline endothelial function, acute exercise improves response to ACh while PUFA supplementation alone or in combination with acute exercise has no effect on endothelium-dependent vasorelaxation. However, PUFA may potentiate the acute exercise effect on smooth muscle cell relaxation via L-type Ca2+ channel modifications.

Fish oil attenuates adrenergic overactivity without altering glucose metabolism during an oral glucose load in haemodialysis patients.

Haemodialysis patients display an increased cardiac mortality, which may be partly related to increased sympathoadrenal activity and insulin resistance. Fish oil decreases adrenal activation induced by mental stress and has an insulin sensitizing effect in healthy subjects. Whole-body glucose metabolism after oral glucose was studied in eight haemodialysis patients before and after a 3-week oral fish oil supplementation (i.e. EPA + DHA at 1.8 g/d). Plasma glucose fluxes were traced by using [6,6- (2)H2]glucose infusion. Substrate oxidation was determined by using indirect calorimetry. Each patient was studied in the basal state and over the 6 h following absorption of a 1 g/kg glucose load. Energy expenditure in response to glucose re-increased over the last 2 h of the experiment (P < 0.05), which coincided with an increase in plasma catecholamines, especially epinephrine (P < 0.05), strongly suggesting a sympathoadrenal overactivity. Fish oil supplementation blunted both re-increase in thermogenic response and concomitant increase in plasma epinephrine, but not in plasma norepinephrine, over the last 2 h of the experiment. Fish oil did not alter either whole-body glucose metabolism or substrate oxidation. These data show that in haemodialysis patients, fish oil attenuates adrenal overactivity induced by oral glucose but does not modulate whole-body glucose metabolism and insulin sensitivity.

Free fatty acids and insulin resistance.

PURPOSE OF REVIEW: Dysregulation of free fatty acid metabolism is a key event responsible for insulin resistance and type 2 diabetes. According to the glucose-fatty acid cycle of Randle, preferential oxidation of free fatty acids over glucose plays a major role in insulin sensitivity and the metabolic disturbances of diabetes mellitus. However, other mechanisms are now described to explain the molecular basis of insulin resistance. RECENT FINDINGS: Recent studies have suggested that local accumulation of fat metabolites such as ceramides, diacylglycerol or acyl-CoA, inside skeletal muscle and liver, may activate a serine kinase cascade leading to defects in insulin signalling and glucose transport. Inflammation and oxidative stress are also potent mechanisms which could lead to a state of insulin resistance. Finally, modulation of transcription by free fatty acids through their binding to peroxisome proliferator-activated receptors could also contribute to impaired glucose metabolism. SUMMARY: The increase in free fatty acid flux resulting from increased lipolysis secondary to adipose-tissue insulin resistance induces or aggravates insulin resistance in liver and muscle through direct or indirect (from triglyceride deposits) generation of metabolites, altering the insulin signalling pathway. Alleviating the excess of free fatty acids is a target for the treatment of insulin resistance.