Omega-3 Fatty Acids are Inversely Related to Callous and Unemotional Traits in Adolescent Boys with Attention Deficit Hyperactivity Disorder

A number of research studies have reported abnormal plasma fatty acid profiles in children with ADHD along with some benefit of n−3 to symptoms of ADHD. However, it is currently unclear whether (lower) long chain-polyunsaturated fatty acids (LC-PUFAs) are related to ADHD pathology or to associated behaviours. The aim of this study was to test whether (1) ADHD children have abnormal plasma LC-PUFA levels and (2) ADHD symptoms and associated behaviours are correlated with LC-PUFA levels. Seventy-two, male children with (n=29) and without a clinical diagnosis of ADHD (n=43) were compared in their plasma levels of LC-PUFA. Plasma DHA was higher in the control group prior to statistical correction. Callous–unemotional (CU) traits were found to be significantly negatively related to both eicosapentaenoic acid (EPA), and total omega-3 in the ADHD group. The findings unveil for the first time that CU and anti-social traits in ADHD are associated with lower omega-3 levels.

A Palatable Hyperlipidic Diet Causes Obesity and Affects Brain Glucose Metabolism in Rats

Background We have previously shown that either the continuous intake of a palatable hyperlipidic diet (H) or the alternation of chow (C) and an H diet (CH regimen) induced obesity in rats. Here, we investigated whether the time of the start and duration of these feeding regimens are relevant and whether they affect brain glucose metabolism. Methods Male Wistar rats received C, H, or CH diets during various periods of their life spans: days 30-60, days 30-90, or days 60-90. Experiments were performed the 60th or the 90th day of life. Rats were killed by decapitation. The glucose, insulin, leptin plasma concentration, and lipid content of the carcasses were determined. The brain was sliced and incubated with or without insulin for the analysis of glucose uptake, oxidation, and the conversion of [1-14C]-glucose to lipids. Results The relative carcass lipid content increased in all of the H and CH groups, and the H30-60 and H30-90 groups had the highest levels. Groups H30-60, H30-90, CH30-60, and CH30-90 exhibited a higher serum glucose level. Serum leptin increased in all H groups and in the CH60-90 and CH30-90 groups. Serum insulin was elevated in the H30-60, H60-90, CH60-90, CH30-90 groups. Basal brain glucose consumption and hypothalamic insulin receptor density were lower only in the CH30-60 group. The rate of brain lipogenesis was increased in the H30-90 and CH30-90 groups. Conclusion These findings indicate that both H and CH diet regimens increased body adiposity independent treatment and the age at which treatment was started, whereas these diets caused hyperglycemia and affected brain metabolism when started at an early age.

Deleterious Effects of Lard-enriched Diet on Tissues Fatty Acids Composition and Hypothalamic Insulin Actions

Altered tissue fatty acid (FA) composition may affect mechanisms involved in the control of energy homeostasis, including central insulin actions. In rats fed either standard chow or a lard-enriched chow (high in saturated/low in polyunsaturated FA, HS-LP) for eight weeks, we examined the FA composition of blood, hypothalamus, liver, and retroperitoneal, epididymal and mesenteric adipose tissues. Insulin-induced hypophagia and hypothalamic signaling were evaluated after intracerebroventricular insulin injection. HS-LP feeding increased saturated FA content in adipose tissues and serum while it decreased polyunsaturated FA content of adipose tissues, serum, and liver. Hypothalamic C20:5n-3 and C20:3n-6 contents increased while monounsaturated FA content decreased. HS-LP rats showed hyperglycemia, impaired insulin-induced hypophagia and hypothalamic insulin signaling. The results showed that, upon HS-LP feeding, peripheral tissues underwent potentially deleterious alterations in their FA composition, whist the hypothalamus was relatively preserved. However, hypothalamic insulin signaling and hypophagia were drastically impaired. These findings suggest that impairment of hypothalamic insulin actions by HS-LP feeding was not related to tissue FA composition.

Dimethyl Acetals, an Indirect Marker of the Endogenous Antioxidant Plasmalogen Level, are Reduced in Blood Lipids of Sudanese Pre-eclamptic Subjects whose Background Diet is High in Carbohydrate

In Sudanese women with (n = 60) and without (n = 65) pre-eclampsia, circulating lipids, plasma and red cell saturated and monounsaturated fatty (MUFA) acids and dimethyl acetals (DMAs) were investigated. DMAs are an indirect marker of levels of plasmalogens, endogenous antioxidants, which play a critical role in oxidative protection, and cholesterol homeostasis. The pre-eclamptics had higher C18:1n-9 (p < 0.001) and ΣMUFA (p < 0.01) in plasma free fatty acids, C16:1n-7, C18:1n-9, ΣMUFA; 16:0/16:1n-7 (p < 0.01) in erythrocyte choline phosphoglycerides (ePC) and 16:1n-7, 18:1n-7 and 16:0/16:1n-7 (p < 0.01) in erythrocyte ethanolamine phosphoglycerides (ePE). In contrast, the DMAs 18:0, 18:1 and ΣDMAs in ePE, and 16:0, 18:0 and ΣDMAs in ePC were reduced (p < 0.001) in the pre-eclamptic women. This study of pregnant women with high carbohydrate and low fat background diet suggests pre-eclampsia is associated with oxidative stress and enhanced activity of the microsomal enzyme stearyl-CoA desaturase (delta 9 desaturase), as assessed by palmitic/palmitoleic (C16:0/C16:n-1) and stearic/oleic (C18/C18:1n-9) ratios.

Effects of Different Fatty Acids and Dietary Lipids on Adiponectin Gene Expression in 3T3-L1 Cells and C57BL/6J Mice Adipose Tissue

Obesity is positively correlated to dietary lipid intake, and the type of lipid may play a causal role in the development of obesity-related pathologies. A major protein secreted by adipose tissue is adiponectin, which has antiatherogenic and antidiabetic properties. The aim of this study was to evaluate the effects of four different high-fat diets (enriched with soybean oil, fish oil, coconut oil, or lard) on adiponectin gene expression and secretion by the white adipose tissue (WAT) of mice fed on a selected diet for either 2 (acute treatment) or 60 days (chronic treatment). Additionally, 3T3-L1 adipocytes were treated for 48 h with six different fatty acids: palmitic, linoleic, eicosapentaenoic (EPA), docosahexaenoic (DHA), lauric, or oleic acid. Serum adiponectin concentration was reduced in the soybean-, coconut-, and lard-enriched diets in both groups. Adiponectin gene expression was lower in retroperitoneal WAT after acute treatment with all diets. The same reduction in levels of adiponectin gene expression was observed in epididymal adipose tissue of animals chronically fed soybean and coconut diets and in 3T3-L1 cells treated with palmitic, linoleic, EPA, and DHA acids. These results indicate that the intake of certain fatty acids may affect serum adiponectin levels in mice and adiponectin gene expression in mouse WAT and 3T3-L1 adipocytes. The effects appear to be time dependent and depot specific. It is postulated that the downregulation of adiponectin expression by dietary enrichment with soybean oil or coconut oil may contribute to the development of insulin resistance and atherosclerosis.

Erythrocyte Phospholipid Molecular Species and Fatty Acids of Down Syndrome Children Compared with Non-affected Siblings

The majority of children with Down syndrome (DS) develop Alzheimer's disease (AD) at an early age. Although long-chain n-3 fatty acids (FA) are protective of neurodegeneration, little is known about the FA status in DS. In the present study, we aimed to investigate whether children with DS presented altered plasma and erythrocyte membrane phospholipids (PL) FA composition, when compared with their non-affected siblings. Venous blood samples were analysed for plasma and erythrocyte membrane FA composition by TLC followed by GC techniques. Lipid molecular species were determined by electrospray ionisation/tandem MS (ESI-MS/MS). FA analysis measured by standard GC showed an increased concentration of MUFA and a decreased concentration of plasmalogens in major PL fractions, but there were no differences in the concentrations of arachidonic acid or DHA. However, as identified by ESI-MS/MS, children with DS had increased levels of the following erythrocyte PL molecular species: 16 : 0–16 : 0, 16 : 0–18 : 1 and 16 : 0–18 : 2n-6, with reduced levels of 16 : 0–20 : 4n-6 species. Children with DS presented significantly higher levels of MUFA in both plasma and erythrocyte membrane, as well as higher levels of saturated and monounsaturated molecular species. Of interest was the almost double proportion of 16 : 0–18 : 2n-6 and nearly half the proportion of 16 : 0–20 : 4n-6 of choline phosphoacylglycerol species in children with DS compared with their non-affected siblings. These significant differences were only revealed by ESI-MS/MS and were not observed in the GC analysis. Further investigations are needed to explore molecular mechanisms and to test the association between the pathophysiology of DS and the risk of AD.

Exercise Training in Rats Impairs the Replenishment of White Adipose Tissue after Partial Lipectomy

The aim of this study was to evaluate the effect of exercise training on the metabolism of rats following the partial removal of fat pads. Three-month-old male Wistar rats were subjected to the partial removal (L) of retroperitoneal white adipose tissue (RET) and epididymal white adipose tissue (EPI), or a sham operation (Sh). Seven days after surgery, both sets of rats were subdivided into exercised (LE or ShE) (swimming 90 min/day, 5 days/week, 6 weeks) and sedentary (LS or ShS) groups. Partial removal of the fat pads increased the lipogenesis rates in both the RET and EPI and decreased the weight and lypolysis rate of the EPI, while the RET weight was not significantly affected by lipectomy. In both lipectomized and sham-operated groups, exercise training caused a reduction in carcass lipid content, food intake, RET and EPI weights, and RET lipogenesis rate. On the other hand, the exercise training increased the percentage of diet-derived lipid accumulation in both tissues, either in sham and lipectomized rats. These results confirmed that regrowth is not uniform and depends on the particular fat pad that is excised. They also demonstrated that exercise training following the partial removal of fat pads modified adipose tissue metabolism, impaired the replenishment of adipose tissue, and decrease body adiposity.

Fructose Alters Adiponectin, Haptoglobin and Angiotensinogen Gene Expression in 3T3-L1 Adipocytes

Fructose- or sucrose-rich diets can cause insulin resistance and increase the risk of cardiovascular disease. Adipokines are correlated with the development of these diseases in obesity. We hypothesize that fructose and sucrose induce insulin resistance via effects on adipokine gene expression in adipocytes. This study analyzed the effect of fructose or glucose on adiponectin, haptoglobin, and angiotensinogen gene expression in 3T3-L1 adipocytes. Ten days after differentiation, the cells were pretreated with serum- and glucose-free medium. Twenty-four hours later, fructose or glucose (0, 5, 10, or 20 mmol) was added into the medium, and the cells were collected after a further 24 hours. Adiponectin, haptoglobin, and angiotensinogen gene expression were determined. Adiponectin gene expression increased when 10 or 20 mmol glucose was added compared with that observed for the non–hexose-treated cells. A similar effect occurred when 5 mmol fructose was added. Glucose (10 mmol) and fructose (20 mmol) stimulated haptoglobin gene expression in 3T3-L1 adipocytes compared with 0 mmol, with glucose producing a more pronounced effect. Although 20 mmol fructose caused an increase in angiotensinogen gene expression, glucose did not. In conclusion, in this study of 2 hexoses revealed an increase in adiponectin gene expression, suggesting that the effect of a glucose-rich diet on the development of insulin resistance is not related to the effect of these hexoses on adipocyte adiponectin gene expression. However, insulin resistance and cardiovascular disease promoted by fructose-rich diets could be partially related to the effect of fructose on adiponectin and angiotensinogen gene expression.

Gut Microbiota, Probiotics and Diabetes

Diabetes is a condition of multifactorial origin, involving several molecular mechanisms related to the intestinal microbiota for its development. In type 2 diabetes, receptor activation and recognition by microorganisms from the intestinal lumen may trigger inflammatory responses, inducing the phosphorylation of serine residues in insulin receptor substrate-1, reducing insulin sensitivity. In type 1 diabetes, the lowered expression of adhesion proteins within the intestinal epithelium favours a greater immune response that may result in destruction of pancreatic β cells by CD8+ T-lymphocytes, and increased expression of interleukin-17, related to autoimmunity. Research in animal models and humans has hypothesized whether the administration of probiotics may improve the prognosis of diabetes through modulation of gut microbiota. We have shown in this review that a large body of evidence suggests probiotics reduce the inflammatory response and oxidative stress, as well as increase the expression of adhesion proteins within the intestinal epithelium, reducing intestinal permeability. Such effects increase insulin sensitivity and reduce autoimmune response. However, further investigations are required to clarify whether the administration of probiotics can be efficiently used for the prevention and management of diabetes.

Hydrogenated Fat Diet Intake during Pregnancy and Lactation Modifies the PAI-1 Gene Expression in White Adipose Tissue of Offspring in Adult Life

We examine whether feeding pregnant and lactating rats hydrogenated fats rich in trans fatty acids modifies the plasma lipid profiles and the expression of adipokines involved with insulin resistance and cardiovascular disease in their 90-day-old offspring. Pregnant and lactating Wistar rats were fed with either a control diet (C group) or one enriched with hydrogenated vegetable fat (T group). Upon weaning, the male pups were sorted into four groups: CC, mothers were receiving C and pups were kept on C; CT, mothers were receiving C and pups were fed with T; TT, mothers were receiving T and pups were kept on T; TC, mothers were receiving T and pups were fed with C. Pups' food intake and body weight were quantified weekly and the pups were killed at day 90 of life by decapitation. Blood and carcass as well as retroperitoneal, epididymal, and subcutaneous white adipose tissues were collected. Food intake and body weight were lower in TC and TT, and metabolic efficiency was reduced in TT. Offspring of TT and TC rats had increased white adipose tissue PAI-1 gene expression. Insulin receptor was higher in TT than other groups. Ingestion of hydrogenated vegetable fat by the mother during gestation and lactation could promote deleterious consequences, even after the withdrawal of the causal factor.

Hydrogenated Fat Intake during Pregnancy and Lactation Modifies Serum Lipid Profile and Adipokine mRNA in 21-day-old Rats

Objective We examined whether feeding pregnant and lactating rats hydrogenated fats rich in trans-fatty acids modifies the plasma lipid profiles and the expression of adipokines involved with insulin resistance and cardiovascular disease in their 21-d-old offspring. Methods Pregnant and lactating Wistar rats were fed with a control diet (C group) or one enriched with hydrogenated vegetable fat (T group). After delivery, male offspring were weighed weekly and killed at day 21 of life by decapitation. Blood and retroperitoneal, epididymal, and subcutaneous white adipose tissues were collected. Results Offspring of T-group rats had increased serum triacylglycerols and cholesterol, white adipose tissue plasminogen activator inhibitor-1, and tumor necrosis factor-α gene expression, and carcass lipid content and decreased blood leptin and adiponectin and adiponectin gene expression. Conclusion Ingestion of hydrogenated vegetable fat by the mother during gestation and lactation alters the blood lipid profiles and the expression of proinflammatory adipokynes by the adipose tissue of offspring aged 21 d.

Lipid Metabolism of Monosodium Glutamate Obese Rats after Partial Removal of Adipose Tissue

We analyzed the effects of partial fat pad removal on retroperitoneal and epididymal fat depots and carcass metabolism of control (C) and MSG-obese (M) rats. Three-month-old C and M male Wistar rats were submitted to either partial surgical excision of epididymal and retroperitoneal fat tissue (lipectomy, L) or sham surgery (S) and studied after 7 or 30 days. Retroperitoneal and epididymal tissue re-growth after lipectomy was not observed, as indicated by the low pads weight of the L groups. The lipolysis rate was stimulated in LC7 and LM7, probably due to surgical stress and low insulin levels. In LM7, but not in LC7, in vivo lipogenesis rate increased in retroperitoneal and epididymal fat tissue, as did the diet-derived lipid accumulation in epididymal fat tissue. Although these local increases were no longer present in LM30, this group showed a large increase in the percentage of small area adipocytes in both pads as well as increased carcass lipogenesis rate. The present data showed that the partial removal of fat depots affected the metabolism of control and MSG-obese rats differently. In the obese animals only, it stimulated both local and carcass lipogenesis rate as well as adipocyte differentiation, i.e. responses likely to favor excised tissue re-growth and/or compensatory growth of non-excised depots.

Long Chain Saturated Fatty Acids Increase Haptoglobin Gene Expression in C57BL/6J Mice Adipose Tissue and 3T3-L1 Cells

Background Dietary lipids are directly related to the composition of adipose tissue, aetiology of obesity and arousal of obesity-related pathologies, like chronic inflammation states. Haptoglobin is an acute phase protein secreted by the liver and white adipose tissue, and its blood levels vary according to the volume of fat in the body. Aim of the study To investigate the effect of diets enriched with large amounts of dietary fats, which differ in their fatty acid composition, on the haptoglobin gene expression by visceral and subcutaneous adipose tissue of mice fed for 2 days or 8 weeks. 3T3-L1 cells were treated with fatty acids that are found in those types of dietary fats. Methods Mice were treated acutely (for 2 days) or chronically (for 8 weeks) with diets enriched with soybean oil, fish oil, coconut oil or lard. 3T3-L1 cells were treated with six different fatty acids. Haptoglobin gene expression was quantified by northern blotting. Results Both chronic and acute treatment with lard, which is rich in long chain saturated fatty acids, increased the haptoglobin mRNA expression in the retroperitoneal and epidydimal white adipose tissues. Chronic treatment with coconut oil, which is rich in medium chain saturated fatty acids, increased the haptoglobin expression in the epidydimal and subcutaneous depots. In 3T3-L1, palmitic acid increased the haptoglobin gene expression. Conclusion The type of lipids in the diet can differently modulate the white adipose tissue gene expression of haptoglobin, and saturated fatty acids play a major role in promoting a pro-inflammatory environment. This response is fat pad specific and dependant on the duration of treatment.

Tubular Urinary Enzymes in Acute Post-infectious Glomerulonephritis

Tubular function of 17 pediatric patients with a mild form of acute post-infectious glomerulonephritis was prospectively evaluated by assessment of the urinary activity of proximal and distal tubule enzymes. Neutral-like endopeptidase (NEP-like) and angiotensin-converting enzyme (ACE) were the proximal tubule enzymes assessed, while prolyl-endopeptidase (PE) and serine-endopeptidase H1 and H2 were the distal tubule enzymes analyzed. Urine was collected at diagnosis (T0) and after 2 (T2) and 6 (T6) months of follow-up. NEP-like enzyme activity (nmol/mg creatinine; median±quartile range) was increased at diagnosis, and this remained stable during the first 6 months (T0 18.30±83.26, T2 17.32±49.56, T6 23.38±107.18). Urinary activity of the other enzymes was as follows: ACE (mU/ml per mg creatinine) T0 0.08±0.16, T2 0.06±0.10, T6 0.18±0.29; PE (nmol/mg creatinine) T0 6.70±84.87, T2 9.55±69.00, T6 13.67±28.70; serine-endopeptidase H1 (nmol/mg creatinine) T0 7.86±26.95, T2 17.17±59.37, T6 18.19± 79.14; and serine-thiol-endopeptidase H2 (nmol/mg creatinine) T0 3.06±21.97, T2 12.06±32.42, T6 16.22± 44.06. Thirty other healthy children matched for age and gender were considered as a control group. This group was assessed once and the results were: NEP-like activity 6.05±10.54, ACE 0.11±0.22, PE 7.10±13.36, H1 5.00±17.30, and H2 6.00±20.16. In conclusion, we observed that NEP-like and H1 enzymes exhibited significant increased urinary activity 6 months after the diagnosis. This increase occurred in spite of the disappearance of clinical symptoms, which occurred 2 months after the diagnosis. We believe that the increase in urinary enzymatic activity could be a manifestation of a silent tubular dysfunction following an episode of acute post-infectious glomerulonephritis.

Outcome of the Public Consultation on the Draft Opinion of the Scientific Panel on Dietetic Products, Nutrition, and Allergies (NDA) on Dietary Reference Values for Fats, Including Saturated Fatty Acids, Polyunsaturated Fatty Acids, Monounsaturated Fatty Acids, Trans Fatty Acids, and Cholesterol

On 2 July 2009, the EFSA Panel on Dietetic products, Nutrition and Allergies (NDA) endorsed a draft Opinion on Dietary Reference Values for fats to be released for public consultation. This Scientific Report summarises the comments received through the public consultation and outlines how these were taken into account in the final opinion. EFSA had received contributions from 40 interested parties (individuals, non-governmental organisations, industry organisations, academia and national assessment bodies). The main comments which were received during the public consultation related to: the availability of more recent data, the nomenclature used, the use of a non-European food composition data base, the impact of genetic factors in modulating the absorption, metabolism and health effects of different fatty acids, the definition of “nutritionally adequate diet”, the use of Dietary Reference Values in the labelling of foods, the translation of advice into food-based dietary guidelines, nutrient goals and recommendations, certain risk management issues, and to Dietary Reference Values of fats, individual fatty acids, and cholesterol. All the public comments received that related to the remit of EFSA were assessed and the Opinion on Dietary Reference Values for fats has been revised taking relevant comments into consideration.