Polyunsaturated fatty acid deficiency affects sulfatides and other sulfated glycans in lysosomes through autophagy-mediated degradation.

Metabolic changes in sulfatides and other sulfated glycans have been related to various diseases, including Alzheimer's disease (AD). However, the importance of polyunsaturated fatty acids (PUFA) in sulfated lysosomal substrate metabolism and its related disorders is currently unknown. We investigated the effects of deficiency or supplementation of PUFA on the metabolism of sulfatides and sulfated glycosaminoglycans (sGAGs) in sulfatide-rich organs (brain and kidney) of mice. A PUFA-deficient diet for over 5 weeks significantly reduced the sulfatide expression by increasing the sulfatide degradative enzymes arylsulfatase A and galactosylceramidase in brain and kidney. This sulfatide degradation was clearly associated with the activation of autophagy and lysosomal hyperfunction, the former of which was induced by suppression of the Erk/mTOR pathway. A PUFA-deficient diet also activated the degradation of sGAGs in the brain and kidney and that of amyloid precursor proteins in the brain, indicating an involvement in general lysosomal function and the early developmental process of AD. PUFA supplementation prevented all of the above abnormalities. Taken together, a PUFA deficiency might lead to sulfatide and sGAG degradation associated with autophagy activation and general lysosomal hyperfunction and play a role in many types of disease development, suggesting a possible benefit of prophylactic PUFA supplementation.

Propionic acid and not caproic acid, attenuates nonalcoholic steatohepatitis and improves (cerebro) vascular functions in obese Ldlr-/- .Leiden mice.

The obesity epidemic increases the interest to elucidate impact of short-chain fatty acids on metabolism, obesity, and the brain. We investigated the effects of propionic acid (PA) and caproic acid (CA) on metabolic risk factors, liver and adipose tissue pathology, brain function, structure (by MRI), and gene expression, during obesity development in Ldlr-/- .Leiden mice. Ldlr-/- .Leiden mice received 16 weeks either a high-fat diet (HFD) to induce obesity, or chow as reference group. Next, obese HFD-fed mice were treated 12 weeks with (a) HFD + CA (CA), (b) HFD + PA (PA), or (c) a HFD-control group. PA reduced the body weight and systolic blood pressure, lowered fasting insulin levels, and reduced HFD-induced liver macrovesicular steatosis, hypertrophy, inflammation, and collagen content. PA increased the amount of glucose transporter type 1-positive cerebral blood vessels, reverted cerebral vasoreactivity, and HFD-induced effects in microstructural gray and white matter integrity of optic tract, and somatosensory and visual cortex. PA and CA also reverted HFD-induced effects in functional connectivity between visual and auditory cortex. However, PA mice were more anxious in open field, and showed reduced activity of synaptogenesis and glutamate regulators in hippocampus. Therefore, PA treatment should be used with caution even though positive metabolic, (cerebro) vascular, and brain structural and functional effects were observed.

Macronutrient composition of the diet and long-term changes in weight and waist circumference in the EPIC-Italy cohort.

BACKGROUND AND AIMS: The overall macronutrient composition of diet, rather than just calorie intake, may influence long-term changes of anthropometry. We investigated relationships between dietary macronutrient composition and long-term changes in weight and waist circumference in participants of the EPIC-Italy - the Italian section of the European Prospective Investigation into Cancer and Nutrition - study. METHODS AND RESULTS: A total of 32,119 participants provided anthropometric measures at recruitment and 12 years later (mean). Diet at recruitment was assessed using validated semi-quantitative food frequency questionnaires. Weight and waist changes associated with replacing 10% of energy from one macronutrient with 10% of energy from another macronutrient were assessed by multivariable linear regression. Increased energy from total protein at the expense of any other macronutrient was significantly associated with increased weight and waist circumference. Increased starch at the expense of sugar and total protein was associated with significantly decreased weight and waist circumference; when starch replaced total fat, weight significantly decreased. Increased sugar at the expense of starch and total fat was significantly associated with increased weight and waist circumference; but increase at the expense of total protein was significantly associated with decreased weight and waist circumference. CONCLUSION: Our results suggest that increasing protein at the expense of fat or carbohydrates, and reducing starch by increasing other macronutrients, might be associated with increased weight and waist gain.

Significant changes in hepatic transcriptome and circulating miRNAs are associated with diet-induced metabolic syndrome in apoE3L.CETP mice.

Long-term exposure to excess dietary fat leads to obesity and the metabolic syndrome (MetS). The purpose of the present study was to identify global changes in liver gene expression and circulating miRNAs in a humanized mouse model of diet-induced MetS. Male apoE3L.CETP mice received a high-fat diet (HFD) or a low-fat diet (LFD) for different time periods and the progression of MetS pathology was monitored. A separate group of mice was divided into responders (R) or nonresponders (NR) and received HFD for 16 weeks. We found that mice receiving the HFD developed manifestations of MetS and displayed an increasing number of differentially expressed transcripts at 4, 8, and 12 weeks compared with mice receiving the LFD. Significantly changed genes were functionally annotated to metabolic diseases and pathway analysis revealed the downregulation of genes in cholesterol and fatty acid biosynthesis and upregulation of genes related to lipid droplet formation, which was in line with the development of hepatic steatosis. In the serum of the apoE3L.CETP mice we identified three miRNAs that were upregulated specifically in the HFD group. We found that responder mice have a distinct gene signature that differentiates them from nonresponders. Comparison of the two diet intervention studies revealed a limited number of common differentially expressed genes but the expression of these common genes was affected in a similar way in both studies. In conclusion, the characteristic hepatic gene signatures and serum miRNAs identified in the present study provide novel insights to MetS pathology and could be exploited for diagnostic or therapeutic purposes.

Association of dairy intake with cardiovascular disease and mortality in 21 countries from five continents (PURE): a prospective cohort study.

BACKGROUND: Dietary guidelines recommend minimising consumption of whole-fat dairy products, as they are a source of saturated fats and presumed to adversely affect blood lipids and increase cardiovascular disease and mortality. Evidence for this contention is sparse and few data for the effects of dairy consumption on health are available from low-income and middle-income countries. Therefore, we aimed to assess the associations between total dairy and specific types of dairy products with mortality and major cardiovascular disease. METHODS: The Prospective Urban Rural Epidemiology (PURE) study is a large multinational cohort study of individuals aged 35-70 years enrolled from 21 countries in five continents. Dietary intakes of dairy products for 136 384 individuals were recorded using country-specific validated food frequency questionnaires. Dairy products comprised milk, yoghurt, and cheese. We further grouped these foods into whole-fat and low-fat dairy. The primary outcome was the composite of mortality or major cardiovascular events (defined as death from cardiovascular causes, non-fatal myocardial infarction, stroke, or heart failure). Hazard ratios (HRs) were calculated using multivariable Cox frailty models with random intercepts to account for clustering of participants by centre. FINDINGS: Between Jan 1, 2003, and July 14, 2018, we recorded 10 567 composite events (deaths [n=6796] or major cardiovascular events [n=5855]) during the 9·1 years of follow-up. Higher intake of total dairy (>2 servings per day compared with no intake) was associated with a lower risk of the composite outcome (HR 0·84, 95% CI 0·75-0·94; ptrend=0·0004), total mortality (0·83, 0·72-0·96; ptrend=0·0052), non-cardiovascular mortality (0·86, 0·72-1·02; ptrend=0·046), cardiovascular mortality (0·77, 0·58-1·01; ptrend=0·029), major cardiovascular disease (0·78, 0·67-0·90; ptrend=0·0001), and stroke (0·66, 0·53-0·82; ptrend=0·0003). No significant association with myocardial infarction was observed (HR 0·89, 95% CI 0·71-1·11; ptrend=0·163). Higher intake (>1 serving vs no intake) of milk (HR 0·90, 95% CI 0·82-0·99; ptrend=0·0529) and yogurt (0·86, 0·75-0·99; ptrend=0·0051) was associated with lower risk of the composite outcome, whereas cheese intake was not significantly associated with the composite outcome (0·88, 0·76-1·02; ptrend=0·1399). Butter intake was low and was not significantly associated with clinical outcomes (HR 1·09, 95% CI 0·90-1·33; ptrend=0·4113). INTERPRETATION: Dairy consumption was associated with lower risk of mortality and major cardiovascular disease events in a diverse multinational cohort. FUNDING: Full funding sources are listed at the end of the paper (see Acknowledgments).

Dietary α-lactalbumin alters energy balance, gut microbiota composition and intestinal nutrient transporter expression in high-fat diet-fed mice.

Recently there has been a considerable rise in the frequency of metabolic diseases, such as obesity, due to changes in lifestyle and resultant imbalances between energy intake and expenditure. Whey proteins are considered as potentially important components of a dietary solution to the obesity problem. However, the roles of individual whey proteins in energy balance remain poorly understood. This study investigated the effects of a high-fat diet (HFD) containing α-lactalbumin (LAB), a specific whey protein, or the non-whey protein casein (CAS), on energy balance, nutrient transporters expression and enteric microbial populations. C57BL/6J mice (n 8) were given an HFD containing either 20 % CAS or LAB as protein sources or a low-fat diet containing CAS for 10 weeks. HFD-LAB-fed mice showed a significant increase in cumulative energy intake (P=0·043), without differences in body weight, energy expenditure, locomotor activity, RER or subcutaneous and epididymal white adipose tissue weight. HFD-LAB intake led to a decrease in the expression of glut2 in the ileum (P=0·05) and in the fatty acid transporter cd36 (P<0·001) in both ileum and jejunum. This suggests a reduction in absorption efficiency within the small intestine in the HFD-LAB group. DNA from faecal samples was used for 16S rRNA-based assessment of intestinal microbiota populations; the genera Lactobacillus, Parabacteroides and Bifidobacterium were present in significantly higher proportions in the HFD-LAB group. These data indicate a possible functional relationship between gut microbiota, intestinal nutrient transporters and energy balance, with no impact on weight gain.

Vitamin K deficiency-induced hemorrhagic shock after thoracentesis: a case report.

BACKGROUND: Vitamin K deficiency results in serious coagulation dysfunction, but hemorrhagic shock is rare. Herein, we describe a case of vitamin K deficiency and abnormality in the path of the intercostal artery, the combination of which led to hemorrhagic shock. CASE PRESENTATION: An 83-year-old woman was hospitalized for suspected gallstones. She developed septic shock after 4 days of hospitalization. We considered cholecystitis or cholangitis and performed abdominal ultrasonography, which revealed gallbladder enlargement, biliary sludge, and hyperplasia of the bile duct wall. Antibiotic treatment with sulbactam/ampicillin (SBT/ABPC) was initiated on day four, and percutaneous transhepatic gallbladder drainage (PTGBD) was performed on day five. The treatment was successful, but the patient developed bilateral pleural effusion because of hypoalbuminemia. We performed drainage for bilateral pleural effusion on days 13 and 17. The patient developed hypotension on day 18; blood tests showed anemia and severe coagulation dysfunction but a normal platelet count. We suspected vitamin K deficiency-induced coagulation dysfunction because of previous antibiotic treatment and restricted diet, and it led to hemorrhagic shock. Massive right hemothorax was observed by computed tomography, and urgent interventional radiology was performed. We observed no injury to the intercostal artery truncus but confirmed an abnormality in the course of the intercostal artery; therefore, we inferred that the cause of hemothorax in this case was injury to a small vessel, not truncus because of the abnormality. Because of the likelihood of rebleeding, we performed coil embolization from the seventh to the ninth intercostal artery. Because we confirmed vitamin K deficiency-induced coagulation dysfunction, we referred to the concentration of protein induced by vitamin K absence/antagonist-II (PIVKA-II), and it was found to increase by 23,000. CONCLUSIONS: A combination of vitamin K deficiency and abnormality in the course of the intercostal artery led to hemorrhagic shock. When using certain antibiotics and restricting diet, it is important to measure coagulation function, even if the platelet count is normal. Further, when thoracentesis is performed, abnormalities in the course of the intercostal artery should be identified. Thoracentesis with ultrasound may prevent hemothorax.

Low-saturated-fat and low-cholesterol diet does not alter pubertal development and hormonal status in adolescents.

AIM: The aim was to assess the influence of dietary counselling on the pubertal development and hormonal status in healthy adolescents. METHODS: We used a subcohort of 193 healthy boys (52%) and girls (48%) from the Special Turku Coronary Risk Factor Intervention Project. Participants were recruited by nurses at the well-baby clinics in Turku Finland in 1990-1992 and randomised into intervention and control groups. Intervention children received low-saturated fat and low-cholesterol dietary counselling initiated at seven months of age. Participants were examined once a year with Tanner staging, anthropometric measurements and serial reproductive hormones from 10 to 19 years of age. In girls, postmenarcheal hormones were not analysed. RESULTS: Pubertal hormones in boys or girls did not differ between the intervention and control groups. However, we observed slight differences in pubertal progression by Tanner staging and in anthropometric parameters. The intervention boys progressed faster to G4 (p = 0.008), G5 (p = 0.008) and P5 (p = 0.03). The intervention boys were taller than control boys (p = 0.04), while weight and body mass index did not differ. CONCLUSION: Dietary intervention did not affect pubertal hormonal status. This finding supports the safety of implemented counselling in respect to puberty.

Chronic Swimming Exercise Ameliorates Low-Soybean-Oil Diet-Induced Spatial Memory Impairment by Enhancing BDNF-Mediated Synaptic Potentiation in Developing Spontaneously Hypertensive Rats.

Exercise and low-fat diets are common lifestyle modifications used for the treatment of hypertension besides drug therapy. However, unrestrained low-fat diets may result in deficiencies of low-unsaturated fatty acids and carry contingent risks of delaying neurodevelopment. While aerobic exercise shows positive neuroprotective effects, it is still unclear whether exercise could alleviate the impairment of neurodevelopment that may be induced by certain low-fat diets. In this research, developing spontaneously hypertensive rats (SHR) were treated with chronic swimming exercise and/or a low-soybean-oil diet for 6 weeks. We found that performance in the Morris water maze was reduced and long-term potentiation in the hippocampus was suppressed by the diet, while a combination treatment of exercise and diet alleviated the impairment induced by the specific low-fat diet. Moreover, the combination treatment effectively increased the expression of brain-derived neurotrophic factor (BDNF) and N-methyl-D-aspartic acid receptor (NMDAR), which were both down-regulated by the low-soybean-oil diet in the hippocampus of developing SHR. These findings suggest that chronic swimming exercise can ameliorate the low-soybean-oil diet-induced learning and memory impairment in developing SHR through the up-regulation of BDNF and NMDAR expression.

Erythrocyte fatty acid composition of Nepal breast-fed infants.

PURPOSE: Essential fatty acids play a critical role in the growth and development of infants, but little is known about the fatty acid status of populations in low-income countries. The objective was to describe the fatty acid composition of red blood cells (RBC) in breastfeed Nepali infants and a subsample of their mothers and to identify the main sources of fatty acids in the mother's diet, as well as the fatty acid composition of breast milk. METHODS: RBC fatty acid composition was analyzed in a random sample of 303 infants and 72 mother, along with 68 breastmilk samples. Fatty acid profiles of the most important dietary fat sources were analyzed. Information on mother's diet and intake of fat was collected by three 24-h dietary recalls. RESULTS: In infant RBC's, docosahexaenoic acid (DHA) was the main n-3 fatty acid, and arachidonic acid (AA) was the major n-6 fatty acid. Total n-6 PUFA was three times higher than total n-3 PUFA. Height-for-age (HAZ) was positively associated with DHA status and AA status in multivariable models. The concentration of all fatty acids was higher in children, compared to mothers, except Total n-6 PUFA and Linoleic acid (LA) where no differences were found. The mother's energy intake from fat was 13% and cooking oil (sesame, mustard, soybean or sunflower oil) contributed 52% of the fat intake. CONCLUSIONS: RBC-DHA levels in both infants and mother was unexpected high taking into account few dietary DHA sources and the low DHA concentrations in breastmilk.

A high salt diet inhibits obesity and delays puberty in the female rat.

BACKGROUND/OBJECTIVES: Processed foods are considered major contributors to the worldwide obesity epidemic. In addition to high sugar and fat contents, processed foods contain large amounts of salt. Owing to the correlations with rising adiposity, salt has recently been proposed to be obesogenic. This study investigated three hypotheses: (i) high salt contributes to weight gain and adiposity in juvenile female rats, (ii) puberty onset would be altered because salt is known to affect neuronal systems involved in activating the reproductive system, and (iii) enhanced adiposity will act synergistically with salt to drive early puberty onset. DESIGN: Female weanling rats (post-natal day 21, n=105) were fed a low fat/low salt diet, low fat/high salt diet, high fat/low salt diet or a high salt/high fat diet for 24 days. Metabolic measures, including weight gain, food intake, fecal output, activity and temperature were recorded in subsets of animals. RESULTS: Body weight, retroperitoneal and perirenal fat pad weight, and adipocyte size were all lower in animals fed high fat/high salt compared with animals fed high fat alone. Leptin levels were reduced in high fat/high salt fed animals compared with high fat/low salt-fed animals. Daily calorie intake was higher initially but declined with adjusted food intake and was not different among groups after 5 days. Osmolality and corticosterone were not different among groups. Fecal analysis showed excess fat excretion and a decreased digestive efficiency in animals fed high fat/low salt but not in animals fed high fat/high salt. Although respiratory exchange ratio was reduced by high dietary fat or salt, aerobic-resting metabolic rate was not affected by the diet. High salt delayed puberty onset, regardless of dietary fat content. CONCLUSIONS: Salt delays puberty and prevents the obesogenic effect of a high fat diet. The reduced weight gain evident in high salt-fed animals is not due to differences in food intake or digestive efficiency.

Dietary fat and breast cancer mortality: A systematic review and meta-analysis.

BACKGROUND: The influence of dietary fat upon breast cancer mortality remains largely understudied despite extensive investigation into its influence upon breast cancer risk. OBJECTIVE: To conduct meta-analyses of studies to clarify the association between dietary fat and breast cancer mortality. DESIGN: MEDLINE and EMBASE were searched for relevant articles published up to March 2012. Risk of all-cause or breast-cancer-specific death was evaluated by combining multivariable adjusted estimates comparing highest versus lowest categories of intake; and per 20 g increase in intake of total and/or saturated fat (g/day) using random-effects meta-analyses. RESULTS: Fifteen prospective cohort studies investigating total fat and/or saturated fat intake (g/day) and breast cancer mortality were included. There was no difference in risk of breast-cancer-specific death (n = 6; HR = 1.14; 95% CI: 0.86, 1.52; p = 0.34) or all-cause death (n = 4; HR = 1.73; 95% CI: 0.82, 3.66; p = 0.15) for women in the highest versus lowest category of total fat intake. Breast-cancer-specific death (n = 4; HR = 1.51; 95% CI: 1.09, 2.09; p < 0.01) was higher for women in the highest versus lowest category of saturated fat intake. CONCLUSIONS: These meta-analyses have shown that saturated fat intake negatively impacts upon breast cancer survival.

The effect of three different ad libitum diets for weight loss maintenance: a randomized 18-month trial.

PURPOSE: To test the effect of three diets in their ability to sustain weight loss and improve type 2 diabetes (T2D) and cardiovascular disease (CVD) risk markers after 18-month intervention. METHODS: Following a ≥8 % weight loss, 131 healthy, overweight/obese (BMI ± SD 31.5 ± 2.6 kg/m2) men (n = 55) and women (n = 76) aged 28.2 ± 4.8 years were randomized to either 1. Moderate fat (40 E%) with 20 E% MUFA and low in glycemic index (GI) (MUFA, n = 54), 2. Low fat (25 E%) and medium in GI (LF, n = 51) or 3. Control (35 E% fat) and high in GI (CTR, n = 26) all with similar protein content, and all provided ad libitum. First 6-month intervention with 100 % food provision (previously reported) following 12 months of moderately intensive intervention with 20 % food provision now reported. RESULTS: Attrition rate was higher in MUFA (63 %) than in LF (37 %, P = 0.019) and CTR (42 %, P = 0.09) group. Weight regain in completers was not different between groups (mean ± SEM), MUFA 7.1 ± 2.1 % versus LF 5.6 ± 1.3 % versus CTR 7.2 ± 1.5 %, nor was body fat regain, MUFA 4.8 ± 1.0 % versus LF 4.7 ± 0.8 % versus CTR 5.7 ± 0.6 %. The MUFA group reduced LDL/HDL ratio by -0.47 ± 0.09 compared with -0.23 ± 0.11 in LF (P < 0.05) and 0.06 ± 0.14 (P < 0.005) in CTR groups. CONCLUSIONS: Weight regain or body composition did not differ between diets over 18 months. No effects on risk markers for T2D or CVD were found, with the exception of an improvement in the LDL/HDL ratio by the MUFA diet compared to the CTR diet. The LF diet was generally more satisfactory and the MUFA diet seemed more difficult to follow.

[Prurigo pigmentosa after fat-reduced diet, treated with doxycycline]. / Prurigo pigmentosa nach fettreduzierter Diät, therapiert mit Doxycyclin.

Prurigo pigmentosa is a rare inflammatory skin disease of unknown origin, mostly described in the ethnic Japanese population. Etiology and pathogenesis are not completely known. Tetracyclines or dapsone are the therapy of choice. A 17-year-old Swiss patient with Turkish parents presented with pruritic rash on the neck and trunk, which started after a diet. Under therapy with doxycycline over 5 weeks, complete healing with slight reticular hyperpigmentation was observed.

Substitution of meat and fish with vegetables or potatoes and risk of myocardial infarction.

Red meat has been suggested to be adversely associated with risk of myocardial infarction (MI), whereas vegetable consumption has been found to be protective. The aim of this study was to investigate substitutions of red meat, poultry and fish with vegetables or potatoes for MI prevention. We followed up 29 142 women and 26 029 men in the Danish Diet, Cancer and Health study aged 50-64 years with no known history of MI at baseline. Diet was assessed by a validated 192-item FFQ at baseline. Adjusted Cox proportional hazard models were used to calculate hazard ratios (HR) and 95 % CI for MI associated with specified food substitutions of 150 g/week. During a median follow-up of 13·6 years, we identified 656 female and 1694 male cases. Among women, the HR for MI when replacing red meat with vegetables was 0·94 (95 % CI 0·90, 0·98). Replacing fatty fish with vegetables was associated with a higher risk of MI (HR 1·23; 95 % CI 1·05, 1·45), whereas an inverse, statistically non-significant association was found for lean fish (HR 0·93; 95 % CI 0·83, 1·05). Substituting poultry with vegetables was not associated with risk of MI (HR 1·00; 95 % CI 0·90, 1·11). Findings for substitution with potatoes were similar to findings for vegetables. Among men, a similar pattern was observed, but the associations were weak and mostly statistically non-significant. This study suggests that replacing red meat with vegetables or potatoes is associated with a lower risk of MI, whereas replacing fatty fish with vegetables or potatoes is associated with a higher risk of MI.

Dietary Fatty Acids: Is it Time to Change the Recommendations?

Limiting the saturated fatty acid (SAFA) consumption forms the basis of dietary fat recommendations for heart health, despite several meta-analyses demonstrating no link between dietary SAFA and the risk of cardiovascular disease (CVD). Three experts on dietary fat and health discussed the evidence of reducing SAFA intake at a symposium of the Federation of European Nutrition Societies in Berlin, Germany, October 23, 2015. Ronald P. Mensink, Maastricht University, the Netherlands, discussed the evidence linking dietary fatty acids and CVD risk. He emphasized the importance of the replacement nutrient(s) when SAFA intake is reduced. Julie Lovegrove, University of Reading, UK, addressed the question of whether higher intakes of unsaturated fatty acids are beneficial. She discussed the replacement of SAFA by polyunsaturated fatty acids (PUFA) and monounsaturated fatty acids (MUFA), noting the reduction in CVD risk with PUFA replacement and in CVD risk markers with MUFA replacement of SAFA. Ursula Schwab, University of Eastern Finland, Kuopio, Finland, discussed the importance of dietary patterns in achieving reduced risk of CVD, observing that several dietary patterns following the principles of a health-promoting diet and adapted to local customs, food preferences and seasonality are effective in reducing the risk of CVD, type 2 diabetes and other chronic diseases. This paper summarizes the symposium presentations.

The challenges of vitamin and mineral supplementation in children with inherited metabolic disorders: a prospective trial.

BACKGROUND: In order to achieve metabolic stability, dietary treatment of inborn errors of metabolism may require restriction of protein, fat or carbohydrate. Manipulation of dietary intake potentially reduces micronutrient status, and provision of a comprehensive vitamin and mineral supplement becomes an essential adjunct to dietary treatment. AIM: To review the efficacy of a new complete vitamin and mineral supplement [Fruitivits, Vitaflo Ltd] in 14 subjects in an open prospective 26-week study. METHOD: All subjects had dietary restrictions: low protein diets (57%, n = 8), regular daytime cornstarch and overnight glucose polymer tube feeds (29%, n = 4), low fat diet (7%, n = 1) and modified Atkins diet (7%, n = 1). Plasma nutritional biochemistry, anthropometry and food frequency questionnaires were collected at week 0, 12 and 26 weeks respectively. RESULTS: Five nutritional parameters showed a significant improvement from baseline (week 0) to study end (week 26): folate (P = 0.01), vitamin E (P = 0.04), plasma selenium (P = 0.002), whole blood selenium (P = 0.04) and total vitamin D (P = 0.008). All the other nutritional markers did not significantly change. Even with regular monitoring, 37% of the product remained unused. CONCLUSIONS: Despite improvements in some nutritional markers, overall use of the vitamin and mineral supplement was less than prescribed. New methods are needed to guarantee delivery of micronutrients in children at risk of deficiencies as a result of an essential manipulation of diet in inborn disorders of metabolism.

Interactive actions of Bdnf methylation and cell metabolism for building neural resilience under the influence of diet.

Quality nutrition during the period of brain formation is a predictor of brain functional capacity and plasticity during adulthood; however it is not clear how this conferred plasticity imparts long-term neural resilience. Here we report that early exposure to dietary omega-3 fatty acids orchestrates key interactions between metabolic signals and Bdnf methylation creating a reservoir of neuroplasticity that can protect the brain against the deleterious effects of switching to a Western diet (WD). We observed that the switch to a WD increased Bdnf methylation specific to exon IV, in proportion to anxiety-like behavior, in Sprague Dawley rats reared in low omega-3 fatty acid diet, and these effects were abolished by the DNA methyltransferase inhibitor 5-aza-2'-deoxycytidine. Blocking methylation also counteracted the reducing action of WD on the transcription regulator CTCF binding to Bdnf promoter IV. In vitro studies confirmed that CTCF binding to Bdnf promoter IV is essential for the action of DHA on BDNF regulation. Diet is also intrinsically associated to cell metabolism, and here we show that the switch to WD downregulated cell metabolism (NAD/NADH ratio and SIRT1). The fact that DNA methyltransferase inhibitor did not alter these parameters suggests they occur upstream to methylation. In turn, the methylation inhibitor counteracted the action of WD on PGC-1α, a mitochondrial transcription co-activator and BDNF regulator, suggesting that PGC-1α is an effector of Bdnf methylation. Results support a model in which diet can build an "epigenetic memory" during brain formation that confers resilience to metabolic perturbations occurring in adulthood.

Association between dietary fat intake and bone mineral density in Korean adults: data from Korea National Health and Nutrition Examination Survey IV (2008 ∼ 2009).

UNLABELLED: We determined the relation between dietary fat intake and bone mineral density, and our study showed that low- as well as high-fat diet was associated with the risk of osteoporosis. Our study provides significant evidence of the specific dietary components that may be important modifiable factors for the prevention of osteoporosis. INTRODUCTION: Osteoporosis and osteoporosis-related fractures have become major public health problems. It is important to understand the various factors that influence bone health and to prevent osteoporosis by correcting modifiable risk factors for the disease. Previous studies suggested that dietary habits and body composition were potent factors associated with bone mineral density. The aim of this study was to determine the independent effect of dietary fat intake on bone mineral density while controlling for other possible confounders, including fat mass and lean body mass. METHODS: This study was based on data obtained in the Fourth Korea National Health and Nutrition Examination Survey. After serial exclusion of subjects according to the selection criteria, 7,192 subjects were included in our analysis. We divided the study population into quintiles according to dietary fat calorie/total calorie intake and compared the adjusted means of bone mineral density between quintiles. RESULTS: The bone mineral density was higher in men and women with a medium fat energy intake compared to those with a low- and high-fat energy intake, but the finding was statistically significant only in women. The results were valid after controlling for body fat percentage and lean body mass. CONCLUSIONS: We found that dietary fat intake is an independent modifiable risk factor for osteoporosis, regardless of body fat or lean body mass, especially in women. However, further investigations with accurate analyses of food intake and nutritional consumption, in addition to long-term follow-up data, are necessary to recommend an osteoporosis-preventive diet in Koreans.

Dietary Fat Modifies the Effects of FTO Genotype on Changes in Insulin Sensitivity.

BACKGROUND: The common variants in the fat mass and obesity-associated (FTO) gene have been associated with obesity and insulin resistance. Recently, studies also linked FTO variants with macronutrient intakes. OBJECTIVE: We aimed to investigate whether diet interventions varying in macronutrients modified the effects of FTO genotypes on changes in insulin resistance. METHODS: We genotyped FTO variants rs1558902 and rs9939609 and measured insulin resistance in fasting plasma samples at baseline and at 6-mo and 2-y visits in 743 overweight or obese adults (aged 30-70 y, 60% women) from a randomized weight-loss dietary interventional trial, the Preventing Overweight Using Novel Dietary Strategies (POUNDS LOST) trial. We assessed interactions between FTO variants and intakes of dietary fat and protein in relation to change in body weight and insulin resistance using generalized estimating equation models. RESULTS: We found significant interactions between rs1558902 and dietary fat on changes in homeostasis model assessment of insulin resistance (HOMA-IR) and insulin (P = 0.003 and 0.004, respectively). Each risk allele (A) of rs1558902 showed a trend to be related to a 0.05-unit less reduction in both log(insulin) and log(HOMA-IR) among the participants assigned to low-fat diets (both P = 0.06), but this was not significantly related to reduction in those assigned to high-fat diets (both P > 0.1) during the 2-y period of intervention. Our data showed that the association between rs9939609 and changes in insulin resistance was not modified by diet macronutrient intakes. CONCLUSIONS: Our results show that carriers of the risk alleles of rs1558902 benefit differently in improving insulin sensitivity by consuming high-fat weight-loss diets rather than low-fat diets. Still, given our data, we acknowledge it is difficult to determine whether fat or carbohydrate contributed to the observed associations.