C4d expression in focal segmental glomerulosclerosis.

BACKGROUND: There is a little information about of expression of C4d (complement fragment) in Focal segmental glomerulosclerosis (FSGS) subtypes. Our aim was to determine the expression of C4d in FSGS subtypes in percutaneous native renal biopsies in a second-level hospital and its correlation with clinical, biochemical and histological variables. MATERIAL AND METHODS: A retrospective study in paraffin blocks of patients with biopsy with FSGS aged 16-65 years, indistinct sex, not diabetic or obese. Immunohistochemistry was performed for C4d and their expression was analyzing in non-sclerosed glomerular capillaries (GC) and sclerosis areas (SA). Clinical and biochemical variables were recorded. The cases were divided into C4d positive and C4d negative groups and compared. The correlation between C4d staining scores in CG and SA with clinical and biochemical variables were analyzed. RESULTS: Twenty samples were analyzed, 4 for each subtype. At the time of biopsy average age 38.8 ±â€¯18.6 years, 65% male, 8.7% were hypertension. The percentage of positivity for C4d was 40% in GC, 30% SA and 35% in mesangium. The highest expression was for cellular and collapsing subtypes. C4d positivity cases had increased proteinuria (p = 0.035). A significant correlation was found between percentage of C4d expression in CG with SA (p = 0.012) and SA with tubular atrophy and interstitial fibrosis (p < 0.05). CONCLUSIONS: C4d expression in FSGS predominated in the cellular and collapsing subtypes, which translates complement activation. C4d is a possible surrogate marker in GSFS.

Curcumin prevents proteins expression changes of oxidative phosphorylation, cellular stress response, and lipid metabolism proteins in liver of mice fed a high-fructose diet.

Increased fructose consumption has been associated with the development of metabolic diseases due to the modification in protein expression, altering metabolic and signaling pathways. Curcumin is a natural compound with a regulatory effect on genes and metabolic pathways. To identify the fructose-induced protein expression changes and the effect of curcumin on the change of protein expression in the liver of mice fed a standard diet and a high fructose diet, to elucidate the global role of curcumin. Four groups (n = 4/group) of male mice (C57BL6J) of six-weeks-old were formed. One group received a standard diet (C); another received curcumin at 0.75% w/w in the feed (C + C); one more received 30% w/v fructose in drinking water (F); and one group received 30% w/v fructose in drinking water and 0.75% w/w curcumin in food (F + C); for 15 weeks. Proteomic analysis was performed by LC-MS/MS, using the label-free technique with the MaxQuant programs for identification and Perseus for expression change analysis. Differentially expressed proteins (fold change ≥1.5 and p < 0.5) were analyzed by gene ontology and KEGG. A total of 1047 proteins were identified, of which 113 changed their expression in mice fed fructose, compared to the control group, and curcumin modified the expression of 64 proteins in mice fed fructose and curcumin compared to mice that only received fructose. Curcumin prevented the change of expression of 13 proteins involved in oxidative phosphorylation (NDUFB8, NDUFB3, and ATP5L) in the cellular response to stress (PSMA5, HIST1H1D) and lipid metabolism (THRSP, DGAT1, ECI1, and ACOT13). Curcumin in mice fed the standard diet increased the expression of proteins related to oxidative phosphorylation, ribosomes, and PPAR pathways. In addition to fructose, increased expression of proteins involved in oxidative phosphorylation, ribosomes, lipid metabolism, and carbon metabolism. However, curcumin prevented expression change in 13 hepatic proteins of fructose-fed mice involved in oxidative phosphorylation, cellular stress response, and lipid metabolism. SIGNIFICANCE: Curcumin is a natural compound with a regulatory effect on proteins and metabolic pathways. So, curcumin prevents the change of expression in 13 hepatic proteins of fructose-fed mice involved in oxidative phosphorylation, cellular stress response and lipid metabolism, as a supplement with protector activity on fructose-induced toxic effects.

Curcumin Prevents the Glycation of Tricarboxylic Acid Cycle and Cell Respiration Proteins in the Heart of Mice Fed with a High-fructose Diet.

BACKGROUND: A high fructose diet (HFD) induces protein glycation. The latter is related to a higher risk of cardiovascular disease. Curcumin is a natural pleiotropic compound that may possess antiglycant properties. OBJECTIVE: The study aims to analyze the effect of curcumin on the content of glycated proteins in the hearts of 6-week-old mice fed with a HFD for 15 weeks. METHODS: Mice were allocated into four groups (n = 6/group): a control group that received a standard diet (CT); a group that received 30% w/v fructose in water (F); a group that received 0.75% w/w curcumin supplemented in food (C); a group that received 30% w/v fructose in water and 0.75% w/w curcumin supplemented in food (F+C). The content of glycated proteins in the heart was determined by Western Blot (whereas the spots were detected by 2D-PAGE) using anti-AGE and anti-CML antibodies. Densitometric analysis was performed using the ImageLab software. Glycated proteins were identified by MALDI-TOF-MS, and an ontological analysis was performed in terms of biological processes and molecular function based on the STRING and DAVID databases. RESULTS: Fourteen glycated protein spots were detected, two of them with anti-AGE and the other 12 with anti- CML. In total, eleven glycated proteins were identified, out of which three had decreased glycation levels due to curcumin exposure. The identified proteins participate in processes such as cellular respiration, oxidative phosphorylation, lipid metabolism, carbohydrate metabolism, the tricarboxylic acid cycle (TAC), and the organization of intermediate filaments. CONCLUSION: Curcumin decreased the fructose-induced glycation level of the ACO2, NDUFS7, and DLAT proteins.

Effect of linagliptin on glucose metabolism and pancreatic beta cell function in patients with persistent prediabetes after metformin and lifestyle.

The goal of the study was to evaluate the effect of adding linagliptin to metformin and lifestyle on glucose levels and pancreatic ß-cell function in patients with persistent impaired glucose tolerance (IGT) after 12 months of metformin and lifestyle. A single center parallel double-blind randomized clinical trial with 6 months of follow-up was performed in patients with persistent IGT after 12 months of treatment with metformin and lifestyle; patients were randomized to continue with metformin 850 mg twice daily (M group, n = 12) or linagliptin/metformin 2.5/850 mg twice daily (LM group, n = 19). Anthropometric measurements were obtained by standard methods and by bioelectrical impedance; glucose was measured by dry chemistry, insulin by chemiluminescence, and pancreatic ß-cell function was calculated with the disposition index using glucose and insulin values during oral glucose tolerance test (OGTT) and adjusting by insulin sensitivity. The main outcomes were glucose levels during OGTT and pancreatic ß-cell function. Patients in the LM group had a reduction in weight (-1.7 ± 0.6, p < 0.05) and body mass index (BMI, -0.67 ± 0.2, p < 0.05). Glucose levels significantly improved in LM group with a greater reduction in the area under the glucose curve during OGTT (AUCGluc0_120min) as compared to the M group (-4425 ± 871 vs -1116 ± 1104 mg/dl/120 min, p < 0.001). Pancreatic ß-cell function measured with the disposition index, improved only in LM group (2.3 ± 0.23 vs 1.7 ± 0.27, p 0.001); these improvements persisted after controlling for OGTT glucose levels. The differences in pancreatic ß-cell function persisted also after pairing groups for basal AUCGluc0_120min. The addition of linagliptin to patients with persistent IGT after 12 months of treatment with metformin and lifestyle, improved glucose levels during OGTT and pancreatic ß-cell function after 6 months of treatment.Trial registration: Clinicaltrials.gov with the ID number NCT04088461.

Effect of a family and interdisciplinary intervention to prevent T2D: randomized clinical trial.

BACKGROUND: Lifestyle changes can reduce the risk of T2D; however, no study has evaluated the effect of a lifestyle intervention involving patients´ family. The aim of this study was to compare the impact of an interdisciplinary family (FI) Vs individual intervention (II) on glucose metabolism, insulin resistance (IR), pancreatic ß-cell function and cardiovascular risk markers in patients with prediabetes, as well as to measure the impact on their families' metabolic risk. METHODS: Randomized Clinical Trial (RCT) to compare the impact of FI and II on IR and pancreatic ß-cell function in subjects with prediabetes. There were 122 subjects with prediabetes (and 101 family members) randomized to FI or II. Data were collected in 2015-2016 and analyzed in 2017-2018. FI group had the support of their family members, who also received personalized diet and exercise recommendations; patients and their family members attended monthly a lifestyle enhancement program. II group received personalized diet and exercise recommendations. The follow-up was for 12 months. Glucose, IR, pancreatic ß-cell function and secondary outcomes (body composition and lipid profile) were assessed at baseline, 6 and 12 months. RESULTS: FI group improved area under the glucose curve (AUC) (from 18,597 ± 2611 to 17,237 ± 2792, p = 0.004) and the Matsuda index (from 3.5 ± 2.3 to 4.7 ± 3.5, p = 0.05) at 12 months. II group improved Disposition Index (from 1.5 ± 0.4 to 1.9 ± 0.73, p < .0001) at 12 months. The improvements achieved in weight and lipids at 6 months, were lost in II group at 12 moths, whereas in FI persisted. Adherence up to 12 months was not different between the study groups (FI 56% Vs II 60%). CONCLUSIONS: FI intervention was more effective by improving glucose AUC, insulin sensitivity and lipid profile, besides that, metabolic risk in family members of the FI group was maintained, while the risk of II group was increased. TRIAL REGISTRATION: This study was retrospectively registered at clinicaltrials.gov on December 15, 2015 (NTC026365646).

Exercise and Sirtuins: A Way to Mitochondrial Health in Skeletal Muscle.

The sirtuins form a family of evolutionarily conserved nicotinamide adenine dinucleotide (NAD)-dependent deacetylases. Seven sirtuins (SIRT1-SIRT7) have been described in mammals, with specific intracellular localization and biological functions associated with mitochondrial energy homeostasis, antioxidant activity, proliferation and DNA repair. Physical exercise affects the expression of sirtuin in skeletal muscle, regulating changes in mitochondrial biogenesis, oxidative metabolism and the cellular antioxidant system. In this context, sirtuin 1 and sirtuin 3 have been the most studied. This review focuses on the effects of different types of exercise on these sirtuins, the molecular pathways involved and the biological effect that is caused mainly in healthy subjects. The reported findings suggest that an acute load of exercise activates SIRT1, which in turn activates biogenesis and mitochondrial oxidative capacity. Additionally, several sessions of exercise (training) activates SIRT1 and also SIRT3 that, together with the biogenesis and mitochondrial oxidative function, jointly activate ATP production and the mitochondrial antioxidant function.

Protein Expression Profile of Twenty-Week-Old Diabetic db/db and Non-Diabetic Mice Livers: A Proteomic and Bioinformatic Analysis.

Type 2 diabetes mellitus is characterized by insulin resistance in the liver. Insulin is not only involved in carbohydrate metabolism, it also regulates protein synthesis. This work describes the expression of proteins in the liver of a diabetic mouse and identifies the metabolic pathways involved. Twenty-week-old diabetic db/db mice were hepatectomized, after which proteins were separated by 2D-Polyacrylamide Gel Electrophoresis (2D-PAGE). Spots varying in intensity were analyzed using mass spectrometry, and biological function was assigned by the Database for Annotation, Visualization and Integrated Discovery (DAVID) software. A differential expression of 26 proteins was identified; among these were arginase-1, pyruvate carboxylase, peroxiredoxin-1, regucalcin, and sorbitol dehydrogenase. Bioinformatics analysis indicated that many of these proteins are mitochondrial and participate in metabolic pathways, such as the citrate cycle, the fructose and mannose metabolism, and glycolysis or gluconeogenesis. In addition, these proteins are related to oxidation⁻reduction reactions and molecular function of vitamin binding and amino acid metabolism. In conclusion, the proteomic profile of the liver of diabetic mouse db/db exhibited mainly alterations in the metabolism of carbohydrates and nitrogen. These differences illustrate the heterogeneity of diabetes in its different stages and under different conditions and highlights the need to improve treatments for this disease.

Aerobic training but no resistance training increases SIRT3 in skeletal muscle of sedentary obese male adolescents.

In recent years, prevalence of obesity in children and adolescents has increased. A strategy for prevention and management of obesity is aerobic training (AT) due to its effectiveness to decrease fat mass. AT increases the content of SIRT3, a mitochondrial protein that increases the expression of PGC-1α and NFR1, thereby enhances mitochondrial function and metabolic health. Resistance training (RT) provides metabolic benefits but its effect on SIRT3 content is unknown. To compare the effect of AT and RT on SIRT3, PGC-1α and NRF-1 protein levels in skeletal muscle of sedentary obese adolescents. Twenty-seven sedentary obese male adolescents (age: 16.7 ± 0.9 years; BMI: 33.7 ± 4.3 kg/m2) completed a 1-month control period prior to randomization to one of two supervised exercise protocols: AT (3 days/week, 40 min/day, 70-80% peak heart rate) or RT (3 days/week, 11 exercises, 2 sets/exercise, 12 repetitions/set) for 12 weeks. Biopsies were obtained from the vastus lateralis muscle before and after 12 weeks to analyse SIRT3, PGC-1α and NRF-1 proteins content. Peak oxygen consumption (VO2peak) and anthropometric variables were evaluated before and after training. AT increased SIRT3 content, which was associated with improvements in PGC-1α content and body fat percentage. RT did not affect SIRT3 or PGC-1α. VO2peak increased only in AT. The increase in muscle mitochondrial SIRT3 was observed only following AT. In contrast, RT increased muscle mass without improving SIRT3 in obese male adolescents.

Muscle irisin response to aerobic vs HIIT in overweight female adolescents.

BACKGROUND: Exercise stimulates the production of fibronectin type III domain-containing protein 5 (FNDC5), which is cleaved to release a protein called irisin. This protein induces browning of white adipose tissue resulting in increased thermogenesis. Different studies have measured circulating irisin at baseline and in response to exercise among a wide variety of individuals; yet, regarding the effect of different exercise intensities in obese adolescent girls, limited insight is available. This study compares the effect of acute aerobic exercise of moderate intensity and high-intensity interval training (HIIT) on irisin levels in skeletal muscle and plasma of sedentary overweight or obese female adolescents. METHODS: The aerobic group (n = 15) and HIIT group (n = 15) underwent anthropometric and metabolic measurements, electrocardiogram, peak oxygen uptake (VO2peak), and two vastus lateralis muscle biopsies before and after session of workout. The session of aerobic exercise included cycling at 65% of their peak heart rate (HRpeak) for 40 min. In the HIIT group, exercise included six bouts of 1 min at 85-95% HRpeak separated by 1 min of recovery. Irisin levels were evaluated in samples of skeletal muscle (western blot) and plasma (ELISA). RESULTS: The levels of expression of irisin in skeletal muscle increased significantly after a session of HIIT (p < 0.05), while aerobic exercise no affect irisin levels. No significant differences between the groups in plasma irisin levels were found. CONCLUSIONS: The increase in muscle irisin levels was observed only following HIIT session. No increases in plasma irisin concentration were observed.

Aerobic Training Increases Expression Levels of SIRT3 and PGC-1α in Skeletal Muscle of Overweight Adolescents Without Change in Caloric Intake.

Sirtuin 3 enzyme (SIRT3) is involved in the regulation of mitochondrial energy homeostasis by activating Peroxisome proliferator-activated receptor-gamma coactivator (PGC-1α). Murine models have shown that the protein SIRT3 was modified by exercise and diet, however, the effect of exercise without diet in humans has not been examined. Propose of this paper was to analyze the effect of aerobic training on SIRT3 and PGC-1α in skeletal muscle of overweight adolescents without change in caloric intake. Fourteen overweight or obese male adolescents (15.5 ± 0.8 years) trained 3 days-week/50 min × session, at 70-80% of maximal heart rate for 12 weeks. Anthropometrics and skeletal muscle biopsies from the vastus lateralis were taken before and after the exercise program to measure adiposity, SIRT3, and PGC-1α proteins. Peak aerobic capacity (VO2peak) was estimated before and after training. The participants did not change their eating habits during the intervention. SIRT3 (1.05 ± 0.11 vs. 1.25 ± 0.14 AU, p = .014) and PGC-1a (1.06 ± 0.15 Vs 1.39 ± 0.20 AU, p = .009) increased. Fat percentage and waist circumference decreased (p < .05). VO2peak increased after training (p < .001). There was a significant association between SIRT3 and PGC-1α after training program. These data suggest that aerobic training increased SIRT3 and PGC-1a expression levels in sedentary, overweight, or obese adolescents.

[Aerobic 12-week training reduces cardiovascular risk factors in overweight teenagers]. / El entrenamiento aeróbico de 12 semanas reduce los factores de riesgo cardiovascular en adolescentes con exceso de peso.

BACKGROUND: Obesity and low cardiorespiratory fitness are risk factors for cardiovascular diseases and type 2 diabetes. AIM: To examine changes in cardiorespiratory fitness and cardiovascular risk factors after an exercise program without any dietary change in sedentary overweight teenagers. METHODS: Fifteen obese young males (15.5 ± 0.8 years, 31.5 BMI ± 5.9 kg/m2) participated in this study. Subjects underwent anthropometric and metabolic measurements, peak oxygen consumption (VO2peak), and lipid profile before and after training. Exercise training consisted of treadmill exercise at 70-80% of heart rate maximal (HRmax) during 50 min, 3 days/week for 12 weeks. Before and after training 24-hour recall was recorded and caloric intake was calculated. RESULTS: Participants did not change their dietary habits during the intervention. Aerobic training diminished the abdominal circumference (p < 0.05), body fat percentage (p < 0.01), and increased VO2peak (p < 0.001). No significant change in body weight, lipid profile, or blood glucose was observed after training. CONCLUSION: Our study shows that 12 weeks of aerobic training improved cardiorespiratory fitness and decreased body fat percentage in overweight male teenagers.