Dietary advanced glycation end products, body composition, and anthropometric measures: A cross-sectional analysis in women with excess body weight.

BACKGROUND AND AIMS: To assess the association between dietary advanced glycation end products (dAGEs) versus body composition and anthropometric variables. METHODS AND RESULTS: Body composition (dual-energy X-ray absorptiometry), anthropometry, and habitual food intake were cross-sectionally evaluated in women with excess body weight and body fat. Mean dAGEs content was estimated using a database containing the Nԑ-(carboxymethyl)lysine (CML) content of 549 foods, which was adjusted by mean energy intake, and categorized into low, medium, and high dAGEs, by the 10th and 50th percentiles of the sample. Associations were tested by linear regression adjusted for age, education, marital status, and physical activity level. Eighty participants had mean ± standard deviation dAGEs 7.85 ± 2.65 AGEs kU/kcal. Compared with high dAGEs, women with low dAGEs ingested more carbohydrate (62% vs. 50% of calories, p < 0.001) and fiber (≈25 g vs. ≈18 g, p = 0.027) and less protein (13% vs. 17% of calories, p = 0.006) and fat (26% vs. 33% of calories, p = 0.011). Women with low dAGEs had waist/hip ratio 0.05 higher than those with high dAGEs (R2 = 0.256, p = 0.005). Low dAGEs relative to medium (p = 0.009) and high (p = 0.002) dAGEs was associated with a ≈5% gynoid fat reduction (R2 = 0.164). CONCLUSION: Low dAGEs was associated with a higher waist/hip ratio and lower percentage of gynoid fat in women with excess body weight and excess body fat. REGISTRATION NUMBER: RBR-7z358j.

Homogenised and pasteurised human milk: lipid profile and effect as a supplement in the enteral diet of Wistar rats.

The retention of human milk (HM) fat in nasogastric probes of infusion pumps can be observed during the feed of infants unable to suck at the mother's breast. The lack of homogenisation of HM could contribute to the fat holding. Therefore, the present study evaluated (i) the influence of homogenisation on milk fat retaining in infant feeding probes and (ii) the in vivo effect of the homogenisation on lipid absorption by Wistar rats. The animals were fed with HM treated following two processing conditions, that is, pasteurised and homogenised-pasteurised. The animals were randomly subdivided into four experimental groups: water-fed (control), pasteurised milk, homogenised-pasteurised milk and pasteurised-skimmed milk. The results of food consumption, mass body gain, corporate metrics and plasma blood levels of total cholesterol did not show any difference (P < 0·05) among the three types of HM used in the experiments. The liver, intestine and intra-abdominal adipose tissue of the four groups of animals presented normal and healthy histology. The composition of fatty acids in the brain tissue of animals fed with homogenised HM increased when compared with the groups fed with non-homogenised HM. These values were 11·08 % higher for arachidonic acids, 6·59 % for DAH and 47·92 % for nervous acids. The ingestion of homogenised HM promoted higher absorption of milk nutrients. Therefore, the addition of the homogenisation stage in HM processing could be an alternative to reduce fat retention in probes and to improve the lipids' absorption in the body.

ß-hydroxy-ß-methylbutyrate supplementation benefits the effects of resistance training on body fat reduction via increased irisin expression in white adipose tissue.

The effects of resistance training (RT) associated with calcium ß-hydroxyß-methylbutyrate (CaHMB) supplementation on the body composition and gene expression of cytokines related to skeletal muscle hypertrophy and adipose tissue metabolism were studied in rats. Male Wistar rats were divided into four groups of 12 animals: sedentary control (SC); sedentary supplemented (SS); resistance training control (RTC) and resistance training supplemented (RTS). Rats from RTC and RTS groups were submitted to an RT programme and those from SS and RTS groups received 1 mL of CaHMB (320 mg kg-1 day-1) by gavage, for 8 weeks. We evaluated: body composition; plasma lipid profile; the gene expression of interleukin (IL)-6, IL-10, IL-15 and fibronectin type III domain-containing protein 5 (FNDC-5) in skeletal muscle, and IL-6, mitochondrial uncoupling protein 1 (UCP-1) in white adipose tissue (WAT); and the concentration of irisin in WAT. Compared to RTC alone, the combination of CaHMB with RT (RTS) further reduced abdominal circumference (5.3%), Lee index (2.4%), fat percentage (24.4%), plasma VLDL cholesterol (16.8%) and triglycerides (17%) and increased the gene expression of FNDC-5 (78.9%) and IL-6 (47.4%) in skeletal muscle and irisin concentration (26.9%) in WAT. Neither RT nor CaHMB affected the protein percentage or the gene expression of IL-6 and UCP-1 in WAT and IL-10, IL-15 in skeletal muscle. In conclusion, CaHMB supplementation increased the beneficial effects of RT on body fat reduction and was associated with muscular genic expression of IL-6 and FNDC-5 and irisin concentration in WAT, despite the lack of change in protein mass and maximal strength.

Author Correction: Neuronal activity regulates DROSHA via autophagy in spinal muscular atrophy.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

LINE-1 in Obesity and Cardiometabolic Diseases: A Systematic Review.

Epigenetic mechanisms may play an important role in the etiology of obesity and cardiometabolic diseases, by activating or silencing the related-genes. Scientific evidence has suggested that LINE-1 methylation is associated with body composition and obesity-related diseases, including insulin resistance, type 2 diabetes mellitus, and cardiovascular disease (CVD). It also has been evaluated as predictor of weight loss. The studies' results are still conflicting, and positive and negative associations have been found to LINE-1 methylation regarding adiposity and cardiometabolic markers. Overall, this review presents observational (cross-sectional and longitudinal) studies and interventions (diet, exercises, and bariatric surgery) that evaluated the relationship of the LINE-1 methylation with obesity, weight loss, dyslipidemias, hypertension, insulin resistance, CVD, and metabolic syndrome. TEACHING POINTS Epigenetic mechanisms may play an important role in the etiology of obesity and cardiometabolic diseases. Many studies have related methylation of LINE-1 with cardiometabolic diseases; however, the results are still controversial. The relationship between the etiology of chronic diseases and the methylation of LINE-1 is not fully elucidated. With advances in epigenetic studies, related mechanisms may be early biomarkers in weight change and cardiometabolic risk.

Meriones unguiculatus infected by Haemonchus contortus: evaluation of different experimental protocols.

Many important studies on resistance reversion, anthelmintic efficacy and, especially, new molecules with antiparasitic effects are performed in laboratories using gerbils (Meriones unguiculatus) as the experimental model. This study aimed to evaluate the use of corticosteroids (dexamethasone and methylprednisolone acetate) in gerbils experimentally infected with different doses of infective larvae (sheathed or exsheathed) of Haemonchus contortus. In the first experiment, 28 gerbils were divided into seven groups infected by 2-6 × 103 larvae, with or without immunosuppression using corticosteroids. In the second experiment, eight gerbils were divided into two groups infected by 2 × 103 sheathed or exsheathed larvae. For the third assay, seven immunosuppressed gerbils were infected with 2 × 103 sheathed larvae and were killed 15 days post infection (PI). The highest number of parasites was recovered from methylprednisolone-immunosuppressed animals. We observed red and white blood cell alterations and biochemical parameters in infected animals that had undergone immunosuppression with methylprednisolone. We highlight that in the first and second experiments a satisfactory number of worms was recovered using sheathed larvae and immunocompetent animals. When exsheathed larvae were used, the number of worms recovered was unsatisfactory. A considerable larval burden was recovered from immunosuppressed gerbils 15 days PI, and body weight did not influence establishment of larvae.

Author Correction: Neuronal activity regulates DROSHA via autophagy in spinal muscular atrophy.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.

Neuronal activity regulates DROSHA via autophagy in spinal muscular atrophy.

Dysregulated miRNA expression and mutation of genes involved in miRNA biogenesis have been reported in motor neuron diseases including spinal muscular atrophy (SMA) and amyotrophic lateral sclerosis (ALS). Therefore, identifying molecular mechanisms governing miRNA expression is important to understand these diseases. Here, we report that expression of DROSHA, which is a critical enzyme in the microprocessor complex and essential for miRNA biogenesis, is reduced in motor neurons from an SMA mouse model. We show that DROSHA is degraded by neuronal activity induced autophagy machinery, which is also dysregulated in SMA. Blocking neuronal activity or the autophagy-lysosome pathway restores DROSHA levels in SMA motor neurons. Moreover, reducing DROSHA levels enhances axonal growth. As impaired axonal growth is a well described phenotype of SMA motor neurons, these data suggest that DROSHA reduction by autophagy may mitigate the phenotype of SMA. In summary, these findings suggest that autophagy regulates RNA metabolism and neuronal growth via the DROSHA/miRNA pathway and this pathway is dysregulated in SMA.

Postprandial Lipid Response to High-Saturated and High-Monounsaturated Fat Meals in Normal-Weight or Overweight Women.

PURPOSE: We evaluated postprandial response of the lipid metabolism markers after the intake of a high-saturated fat (HSM) or high-monounsaturated fat meal (HMM). METHODS: A randomized, controlled and acute intervention study included 63 women (age 26.9 ± 6.1 years): 35 normal weight (NW) and 28 overweight (OW) (total body fat [TBF] 24.7 ± 3.9% and 36.6 ± 3.9%, respectively). After 12 hours of fasting, each subject was given one of the two test meals standardized, including 2 muffins and water (HSM, 42.1% of saturated fat acid, or HMM, 34.5% of monounsaturated fat acid). Plasma fatty acid profile and concentrations of apolipoproteins A1 and B100, complement C3, and triacylglycerols were analyzed during fasting and at 2, 3, and 5 postprandial hours. RESULTS: Among the markers studied, the triacylglycerol (TAG) and complement C3 were significantly higher in the OW group, compared to NW. The increment in the C3 concentration was higher after HSM intake, compared with HMM (iAUC = 4365.5 ± 5477.4 vs. 1215.2 ± 882.4; p = 0.006), with no differences between groups. After 5 hours postprandial, plasma oleic acid values remained high compared with the fasting value in the NW group, but not in the OW group (26.0 ± 4.2 vs 23.7 ± 3.9%; p < 0.001). Women with high percentage of total plasma saturated fatty acids (SFA) at the beginning of the intervention had higher incremental area under the curve (iAUC) for the palmitic, stearic, and total fatty acids (p < 0.005). Those women with a high percentage of monounsaturated fatty acids (MUFA) showed lower iAUC values for the same fatty acid profile (p < 0.005). CONCLUSION: This study demonstrated the effect of the HSM on postprandial increment of C3 concentration, suggesting another mechanism for saturated fat metabolism. The postprandial response to HSM appears to be the mediated by baseline lipid profile of the individuals, while the response to HMM was correlated to the weight status.

Decreased microRNA levels lead to deleterious increases in neuronal M2 muscarinic receptors in Spinal Muscular Atrophy models.

Spinal Muscular Atrophy (SMA) is caused by diminished Survival of Motor Neuron (SMN) protein, leading to neuromuscular junction (NMJ) dysfunction and spinal motor neuron (MN) loss. Here, we report that reduced SMN function impacts the action of a pertinent microRNA and its mRNA target in MNs. Loss of the C. elegans SMN ortholog, SMN-1, causes NMJ defects. We found that increased levels of the C. elegans Gemin3 ortholog, MEL-46, ameliorates these defects. Increased MEL-46 levels also restored perturbed microRNA (miR-2) function in smn-1(lf) animals. We determined that miR-2 regulates expression of the C. elegans M2 muscarinic receptor (m2R) ortholog, GAR-2. GAR-2 loss ameliorated smn-1(lf) and mel-46(lf) synaptic defects. In an SMA mouse model, m2R levels were increased and pharmacological inhibition of m2R rescued MN process defects. Collectively, these results suggest decreased SMN leads to defective microRNA function via MEL-46 misregulation, followed by increased m2R expression, and neuronal dysfunction in SMA.

Milk kefir: nutritional, microbiological and health benefits.

Kefir is fermented milk produced from grains that comprise a specific and complex mixture of bacteria and yeasts that live in a symbiotic association. The nutritional composition of kefir varies according to the milk composition, the microbiological composition of the grains used, the time/temperature of fermentation and storage conditions. Kefir originates from the Caucasus and Tibet. Recently, kefir has raised interest in the scientific community due to its numerous beneficial effects on health. Currently, several scientific studies have supported the health benefits of kefir, as reported historically as a probiotic drink with great potential in health promotion, as well as being a safe and inexpensive food, easily produced at home. Regular consumption of kefir has been associated with improved digestion and tolerance to lactose, antibacterial effect, hypocholesterolaemic effect, control of plasma glucose, anti-hypertensive effect, anti-inflammatory effect, antioxidant activity, anti-carcinogenic activity, anti-allergenic activity and healing effects. A large proportion of the studies that support these findings were conducted in vitro or in animal models. However, there is a need for systematic clinical trials to better understand the effects of regular use of kefir as part of a diet, and for their effect on preventing diseases. Thus, the present review focuses on the nutritional and microbiological composition of kefir and presents relevant findings associated with the beneficial effects of kefir on human and animal health.

Review of the mechanisms of probiotic actions in the prevention of colorectal cancer.

The purpose of this review is to discuss the potential mechanisms of probiotics action in colorectal cancer prevention. In this regard, the composition of the intestinal microbiota is considered as an important risk factor in the development of colorectal cancer, and probiotics are able to positively modulate the composition of this microbiota. Studies have shown that the regular consumption of probiotics could prevent the development of colorectal cancer. In this respect, in vitro and experimental studies suggest some potential mechanisms responsible for this anticarcinogenic action. The mechanisms include modification of the intestinal microbiota composition, changes in metabolic activity of the microbiota, binding and degradation of carcinogenic compounds present in the intestinal lumen, production of compounds with anticarcinogenic activity, immunomodulation, improvement of the intestinal barrier, changes in host physiology, inhibition of cell proliferation, and induction of apoptosis in cancer cells. In contrast, very few reports demonstrate adverse effects of probiotic oral supplementation. In light of the present evidence, more specific studies are needed on probiotic bacteria, especially regarding the identification of the bacterial strains with greater anticarcinogenic potential; the verification of the viability of these strains after passing through the gastrointestinal tract; the investigation of potential adverse effects in immunocompromised individuals; and finally establishing the dosage and frequency of use.

Dysregulation of RNA Mediated Gene Expression in Motor Neuron Diseases.

Recent findings indicate an important role for RNA-mediated gene expression in motor neuron diseases, including ALS (amyotrophic lateral sclerosis) and SMA (spinal muscular atrophy). ALS, also known as Lou Gehrig's disease, is an adult-onset progressive neurodegenerative disorder, whereby SMA or "children's Lou Gehrig's disease" is considered a pediatric neurodevelopmental disorder. Despite the difference in genetic causes, both ALS and SMA share common phenotypes; dysfunction/loss of motor neurons that eventually leads to muscle weakness and atrophy. With advanced techniques in molecular genetics and cell biology, current data suggest that these two distinct motor neuron diseases share more than phenotypes; ALS and SMA have similar cellular pathological mechanisms including mitochondrial dysfunction, oxidative stress and dysregulation in RNA-mediated gene expression. Here, we will discuss the current findings on these two diseases with specific focus on RNA-mediated gene regulation including miRNA expression, pre-mRNA processing and RNA binding proteins.

Kefir reduces insulin resistance and inflammatory cytokine expression in an animal model of metabolic syndrome.

There is growing evidence that kefir can be a promising tool in decreasing the risk of many diseases, including metabolic syndrome (MetS). The aim of the present study was to evaluate the effect of kefir supplementation in the diet of Spontaneously Hypertensive Rats (SHR) in which MetS was induced with monosodium glutamate (MSG), and to determine its effect on metabolic parameters, inflammatory and oxidation marker expression and glycemic index control. Thirty animals were used in this experiment. For the induction of MetS, twenty two-day-old male SHR received five consecutive intradermal injections of MSG. For the Negative Control, ten newborn male SHR received intradermal injections of saline solution (0.9% saline solution). After weaning, animals received standard diet and water ad libitum until reaching 3 months old, for the development of MetS. They were then divided into three groups (n = 10): negative control (NC, 1 mL saline solution per day), positive control (PC, 1 mL saline solution per day) and the Kefir group (1 mL kefir per day). Feeding was carried out by gavage for 10 weeks and the animals received standard food and water ad libitum. Obesity, insulin resistance, pro- and anti-inflammatory markers, and the histology of pancreatic and adipose tissues were among the main variables evaluated. Compared to the PC group, kefir supplementation reduced plasma triglycerides, liver lipids, liver triglycerides, insulin resistance, fasting glucose, fasting insulin, thoracic circumference, abdominal circumference, products of lipid oxidation, pro-inflammatory cytokine expression (IL-1ß) and increased anti-inflammatory cytokine expression (IL-10). The present findings indicate that kefir has the potential to benefit the management of MetS.

Anaemia, Serum Iron Concentrations and δ-Aminolevulinate Dehydratase Activity in Laying Hens Infected Naturally by Salmonella Gallinarum.

The aim of this study was to evaluate anaemia, serum iron concentrations and δ-aminolevulinate dehydratase (ALA-D) activity in laying hens infected naturally by Salmonella Gallinarum and having severe hepatic lesions. Liver and serum samples were collected from 27 laying hens (20 infected and seven uninfected). The δ-ALA-D activity, haematocrit and serum iron concentrations were evaluated. There were significant decreases in δ-ALA-D activity, haematocrit and serum iron concentrations (P <0.01) in birds infected by S. Gallinarum when compared with uninfected birds. There was a positive correlation (P <0.001) between serum iron concentration, haematocrit (r(2) = 0.82) and δ-ALA-D activity (r(2) = 0.75). A positive correlation was also observed between δ-ALA-D activity and haematocrit (r(2) = 0.78; P <0.01). Liver samples showed moderate focal coagulative necrosis associated with infiltration of lymphoplasmacytic cells, macrophages and heterophils. The anaemia in the infected hens may be related to reduction in δ-ALA-D activity and serum iron concentrations, since both are important for haemopoiesis.

Relationship Between Pathological Findings and Cholinesterase Activity and Nitric Oxide Levels in Cattle Infected Naturally by Eurytrema coelomaticum.

The aim of this study was to evaluate the role of butyrylcholinesterase (BChE) (in the serum and pancreas), acetylcholinesterase (AChE) (in the whole blood and pancreas) and nitric oxide (NO) (in the serum and pancreas) in cattle infected naturally by Eurytrema coelomaticum. Fifty-one cattle were studied, including 33 infected by E. coelomaticum and 18 uninfected animals. Significantly greater AChE activity was found in the pancreas of infected animals (P <0.01); however, these cattle had lower AChE activity in whole blood. BChE activity was greater in the sera of infected animals (P = 0.05), but was less in pancreatic samples. NO levels were significantly higher in the sera (P <0.05) and pancreas (P <0.001) of infected cattle compared with uninfected animals. A positive correlation was found between AChE activity in the pancreas and parasite load, but there was negative correlation between pancreatic BChE activity and parasitic load. Expression of AChE, BChE and NO is therefore linked to the inflammation caused by E. coelomaticum in cattle.

Main characteristics of metabolically obese normal weight and metabolically healthy obese phenotypes.

In this review, the influence of fat depots on insulin resistance and the main characteristics of metabolically obese normal-weight and metabolically healthy obese phenotypes are discussed. Medline/PubMed and Science Direct were searched for articles related to the terms metabolically healthy obesity, metabolically obese normal weight, adipose tissue, and insulin resistance. Normal weight and obesity might be heterogeneous in regard to their effects. Fat distribution and lower insulin sensitivity are the main factors defining phenotypes within the same body mass index. Although these terms are interesting, controversies about them remain. Future studies exploring these phenotypes will help elucidate the roles of adiposity and/or insulin resistance in the development of metabolic alterations.

Normal esophageal pressure topography metrics for data derived from the Sandhill-Unisensor high-resolution manometry assembly in supine and sitting positions.

BACKGROUND: Normal values of the esophageal motor function parameters for high-resolution manometry (HRM-EPT) adopted by the Chicago classification were established using the proprietary system of Given Imaging. It is conceivable that normal values of a system do not apply to data from others. Most studies using HRM were based on supine swallows, whereas deglutition occurs mostly in the upright position. We wished to establish normal values for HRM-EPT parameters obtained with the Sandhill's HRM-EPT system and compare the results in supine and sitting positions. METHODS: Sixty-nine healthy volunteers, 38 females, median age 27 years, were included in this study. All underwent supine HRM, and 34 of them underwent sitting HRM, with at least 10 single 5-mL swallows for analysis obtained in each position. KEY RESULTS: The normal range (5-95th percentiles) for the following parameters was calculated: distal contractile integral (DCI), 606-4998 mmHg·s·cm; contractile front velocity (CFV), 2.0-6.5 cm/s; distal latency (DL), 5.1-8.8 s; intrabolus pressure (IBP), 1.9-17.6 mmHg; upper esophageal sphincter (UES) pressure, 45.2-186.9 mmHg; esophagogastric junction (EGJ) length, 1.8-4 cm; EGJ resting pressure, 8.1-61.6 mmHg, and integrated relaxation pressure (IRP) 2.5-23.5 mmHg. Normal values of EGJ resting pressure, IRP, DCI, and IBP but not CFV, DL, and UES resting pressure were significantly lower in the sitting posture. CONCLUSIONS & INFERENCES: Studies performed with Sandhill's HRM-EPT system should use its own specific normal data. Normal values should be established for different study.

Red but not white meat consumption is associated with metabolic syndrome, insulin resistance and lipid peroxidation in Brazilian middle-aged men.

BACKGROUND: The influence of diet on metabolic syndrome and oxidative stress are not completely known. DESIGN: This cross-sectional study assessed the association of red meat and white meat consumption with metabolic syndrome, insulin resistance and lipid peroxidation in Brazilian middle-aged men. METHODS: A total of 296 subjects (age: 50.5 ± 5.0 years, body mass index: 25.8 ± 3.5 kg/m(2)) were evaluated. Anthropometry, lifestyle features, blood biochemical parameters, diagnosis of metabolic syndrome, homeostatic model assessment for insulin resistance, a lipid peroxidation marker (oxidized low-density lipoprotein) and triglycerides:high-density lipoprotein cholesterol ratio were assessed. Dietary intake was estimated by a food frequency questionnaire. RESULTS: The subjects included in the highest tertile red meat (≥81.5 g/d) and saturated fatty acid from red meat consumption (≥4.3 g/d) had higher occurrence of central obesity (nearly 60%, p < 0.01), hypertriglyceridaemia (nearly 43%, p < 0.01) and metabolic syndrome (35%, p < 0.01). They also had higher values of homeostatic model assessment for insulin resistance, oxidized low-density lipoprotein, and triglycerides:high-density lipoprotein cholesterol ratio, regardless of interfering factors. There were no associations of highest white meat tertile (≥39.4 g/d) and saturated fatty acid from white meat (≥1.0 g/d) consumption with the assessed parameters (p > 0.05). CONCLUSIONS: Red meat consumption was cross-sectionally associated with the occurrence of central obesity, hypertriglyceridaemia, and metabolic syndrome as well as with higher homeostatic model assessment for insulin resistance, oxidized low-density lipoprotein concentrations and triglycerides:high-density lipoprotein cholesterol ratio. The content of saturated fatty acid from red meat consumption may be a factor that contributed to this relationship, while white meat consumption was not associated with metabolic syndrome and the assessed biomarkers.