(-)-epicatechin treatment did not modify the thermogenic pathway in the gastrocnemius muscle of male rat offspring obeses by programming.

The aim of this study was to analyse the expression of genes related to the regulation of energy metabolism in skeletal muscle tissue by comparing male offspring in two age groups [at 110 and 245 postnatal days (pnd)] from a mother with obesity induced by a high-fat diet and (-)-epicatechin (Epi) administration. Four groups of six male offspring from different litters were randomly selected for the control groups [C and offspring of mothers with maternal obesity (MO)] or Epi intervention groups. We evaluated the effect of Epi on gastrocnemius tissue by analysing the mRNA and protein expression levels of Fndc5/irisin, Pgc-1α, Ucp3, and Sln. Epi significantly increased the Pgc-1α protein in the MO group of offspring at 110 pnd (p < 0.036, MO vs. MO+Epi), while at 245 pnd, Epi increased Fndc5/irisin mRNA expression in the MO+Epi group versus the MO group (p = 0.006).No differences were detected in Fndc5/irisin, Ucp3 or Sln mRNA or protein levels (including Pgc-1α mRNA) in the offspring at 110 pnd or in Pgc-1α, Ucp3, or Sln mRNA or protein levels (including Fndc5/irisin protein) at 245 pnd among the experimental groups. In conclusion, (-)-epicatechin treatment increased Fndc5/irisin mRNA expression and Pgc-α protein levels in the gastrocnemius muscle of offspring at postnatal days 110 and 245. Furthermore, it is suggested that the flavonoid effect in a model of obesity and its impact on thermogenesis in skeletal muscle are regulated by a different pathway than Fndc5/irisin.

RS3480 Polymorphism of FNDC5/Irisin Is Associated with Type 2 Diabetes Mellitus in Maya-Mestizo Women.

Objective: To investigate the possible association between rs3480 and rs16835198 of the fibronectin type III domain containing 5 (FNDC5)/Irisin and their haplotypes with the presence of type 2 diabetes mellitus (T2DM) in Maya-Mestizo women. Methods: We studied 547 postmenopausal women of Maya-Mestizo origin. The diagnosis of T2DM was based on the criteria of the American Diabetes Association. DNA was obtained from blood leukocytes. rs3480 and rs16835198 of FNDC5/Irisin were studied using real-time polymerase chain reaction allelic discrimination. Deviations from Hardy-Weinberg equilibrium and alleles differences, as well as genotype frequencies between groups, were assessed by χ2 tests. Using logistic regression analysis, the odds ratio and 95% confidence intervals were calculated to estimate the association between both polymorphisms of FNDC5/Irisin and the presence of T2DM. Pairwise linkage disequilibrium between polymorphisms was calculated by direct correlation r2, and haplotype analysis was conducted. Results: We found that the G-allele of rs3480, as well as under a dominant model, this polymorphism was significantly associated with T2DM (P = 0.028 and P = 0.003, respectively). Besides, one haplotype was associated with T2DM (P = 0.035). Conclusions: Our results suggest that the FNDC5/Irisin rs3480, and one haplotype formed by rs3480 and rs16835198 were associated with the risk of presenting T2DM in Maya-Mestizo women.

Differential histological features and myogenic protein levels in distinct muscles of d-sarcoglycan null muscular dystrophy mouse model.

Skeletal muscle (SkM) comprises slow and fast-twitch fibers, which differ in molecular composition, function, and systemic energy consumption. In addition, muscular dystrophies (DM), a group of diverse hereditary diseases, present different patterns of muscle involvement, progression, and severity, suggesting that the regeneration-degeneration process may differ depending on the muscle type. Therefore, the study aimed to explore the expression of proteins involved in the repair process in different muscles at an early stage of muscular dystrophy in the δ-sarcoglycan null mice (Sgcd-null), a limb-girdle muscular dystrophy 2 F model. Hematoxylin & Eosin (H&E) Staining showed a high number of central nuclei in soleus (Sol), tibialis (Ta), gastrocnemius (Gas), and extensor digitorum longus (Edl) from four months Sgcd-null mice. However, fibrosis, determined by trichrome of Gomori modified staining, was only observed in Sgcd-null Sol. In addition, the number of Type I and II fibers variated differentially in the Sgcd-null muscles vs. wild-type muscles. Besides, the protein expression level of ß-catenin, myomaker, MyoD, and myogenin also presented different expression levels in all the Sgcd-null muscles studied. In summary, our study reveals that muscles with different metabolic characteristics showed distinct expression patterns of proteins involved in the muscle regeneration process. These results could be relevant in designing therapies for genetic and acquired myopathy.

(-)-Epicatechin increases apelin/APLNR expression and modifies proteins involved in lipid metabolism of offspring descendants of maternal obesity.

Several studies have shown the beneficial effects of (-)-epicatechin (Epi) in metabolic profile and that this flavanol is a biased ligand of the apelin receptor. The apelinergic system is expressed in adipocytes and has been related to obesity and metabolic disorders. The study aim was to evaluate the effect of Epi on apelin, on its receptor and on proteins involved in lipolysis, lipogenesis, and adipogenesis in the retroperitoneal adipose tissue of male rats descended from obese mothers. We evaluated the effect of Epi in the retroperitoneal adipose tissue of four groups of male offspring, analyzing mRNA expression and protein levels of apelin and its Apj receptor. We also analyzed, by Western Blot, the levels of AMPKα, ACC, C/EBPα, ATGL, Fas, and FABP4 of the AP2 proteins. Epi significantly elevated apelin mRNA expression and protein levels as well as its Apj receptor. Besides, the flavanol significantly promoted AMPKα phosphorylation with the concomitant reduction of Fas, and the increase of the ATGL protein. In contrast, there was an increase in the inactive phosphorylated form of ACC and a decrease in the phosphorylated active form of C/EBPα. Similarly, Epi treatment induced a reduction in the fatty acid-binding protein 4 in the C+Epi and MO+Epi groups. In conclusion, Epi increases the expression of the apelinergic system and the active phosphorylated form of AMPKα; likewise, it modifies the expression level or active form of proteins involved in lipolysis, lipogenesis and adipogenesis in the retroperitoneal adipose tissue of male offspring of obese mothers.

High-fat diet consumption by male rat offspring of obese mothers exacerbates adipose tissue hypertrophy and metabolic alterations in adult life.

Obese mothers' offspring develop obesity and metabolic alterations in adulthood. Poor postnatal dietary patterns also contribute to obesity and its comorbidities. We aimed to determine whether in obese mothers' offspring an adverse postnatal environment, such as high-fat diet (HFD) consumption (second hit) exacerbates body fat accumulation, metabolic alterations and adipocyte size distribution. Female Wistar rats ate chow (C-5 %-fat) or HFD (maternal obesity (MO)-25 %-fat) from weaning until the end of lactation. Male offspring were weaned on either control (C/C and MO/C, maternal diet/offspring diet) or HFD (C/HF and MO/HF) diet. At 110 postnatal days, offspring were killed. Fat depots were excised to estimate adiposity index (AI). Serum glucose, triglyceride, leptin, insulin, insulin resistance index (HOMA-IR), corticosterone and dehydroepiandrosterone (DHEA) were determined. Adipocyte size distribution was evaluated in retroperitoneal fat. Body weight was similar in C/C and MO/C but higher in C/HF and MO/HF. AI, leptin, insulin and HOMA-IR were higher in MO/C and C/HF v. C/C but lower than MO/HF. Glucose increased in MO/HF v. MO/C. C/HF and MO/C had higher triglyceride and corticosterone than C/C, but lower corticosterone than MO/HF. DHEA and the DHEA/corticosterone ratio were lower in C/HF and MO/C v. C/C, but higher than MO/HF. Small adipocyte proportion decreased while large adipocyte proportions increased in MO/C and C/HF v. C/C and exacerbated in MO/HF v. C/HF. Postnatal consumption of a HFD by the offspring of obese mothers exacerbates body fat accumulation as well as the decrease of small and the increase of large adipocytes, which leads to larger metabolic abnormalities.

Variations in protein levels of the apelinergic system in adipose tissue of hypertensive individuals with class 3 obesity.

The aim of this study was to investigate the expression of apelin (APLN) and its receptor (APLNR) in visceral adipose tissue (VAT), and its effect on the downstream expression of endothelial nitric oxide synthase (eNOS) in individuals with class 3 obesity, with or without hypertension. Seventy-five unrelated individuals presenting obesity class 3 with or without hypertension were included. Gene expression of APLN, and APLNR were analyzed in VAT, by reverse transcription quantitative polymerase chain reaction. The APLN, APLNR and eNOS (total and phosphorylated) levels in VAT were evaluated by Western blot. Analysis of differences between groups of APLN, APLNR and eNOS were performed by a logistic regression adjusting by confounding factors. Forty-five individuals with hypertension formed the case group, and 30 individuals constituted the control group. The APLN mRNA and protein levels were higher in the group of individuals with hypertension versus individuals without hypertension (p = 0.027 and p = 0.036, respectively). Meanwhile, APLNR mRNA and protein levels in subjects with hypertension were lower versus the group of subjects without hypertension (p = 0.001 and p = 0.008, respectively). Further, the group with hypertension presented a lower level of phosphorylation of eNOS Ser1177, compared to the control group (p = 0.002). In conclusion, individuals with class 3 obesity and hypertension present a modified APLN/APLNR expression in visceral adipose tissue, which could be secondary to reduced eNOS phosphorylation.

(-)-Epicatechin modulates the expression of myomiRs implicated in exercise response in mouse skeletal muscle.

The flavanol (-)-epicatechin has exercise-mimetic properties. Besides, several miRNAs play a role in modulating the adaptation of the muscle to different training protocols. However, notwithstanding all information, few studies aimed to determine if (-)-epicatechin can modify the expression of miRNAs related to skeletal muscle development and regeneration. Mice were treated for fifteen days by oral gavage with the flavanol (-)-epicatechin. After treatment, the quadriceps of the mice was dissected, and total RNA was extracted. The expression level of miR-133, -204, -206, -223, -486, and -491 was analyzed by qRT-PCR. We also used bioinformatic analysis to predict the participation of these miRNAs in different skeletal muscle signal transduction pathways. Additionally, we analyzed the level of the myogenic proteins MyoD and myogenin by Western blot and measured the cross-sectional area of muscle fibers stained with E&H. (-)-Epicatechin upregulated the expression of miR-133, -204, -206, -223, and -491 significantly, which was associated with an increase in the level of the myogenic proteins MyoD and Myogenin and an augment in the fiber size. The bioinformatics analysis showed that the studied miRNAs might participate in different signal transduction pathways related to muscle development and adaptation. Our results showed that (-)-epicatechin upregulated miRNAs that participate in skeletal exercise muscle adaptation, induced muscle hypertrophy, and increased the level of myogenic proteins MyoD and MyoG.

Association of polymorphisms rs2303729, rs10880, and rs1131620 of LTBP4 with sarcopenia in elderly patients with type 2 diabetes mellitus.

BACKGROUND: Latent TGFß binding protein 4 (LTBP4) modifies skeletal muscle function, and polymorphisms in this gene have been associated with a longer ambulation time in patients with Duchenne muscular dystrophy. However, no studies associate these polymorphisms with an acquired muscle condition. AIM: The study aims to determine whether three functional variants within the LTBP4 were associated with sarcopenia in patients with type 2 diabetes mellitus (T2DM). SUBJECTS AND METHODS: We performed an analysis with 144 elderly individuals with T2DM, including 101 without sarcopenia and 43 with sarcopenia. Polymorphism frequency was determined by real-time PCR allelic discrimination TaqMan assay. RESULTS: Under different genetic models, the univariant analysis did not show a significant association of any polymorphism with sarcopenia. But the multivariate model analysis showed that variant rs1131620 (OR 7.852, 95% CI 1.854-33.257, p = 0.005) was significantly associated with sarcopenia under a dominant model. Under the same analysis, the variants rs2303729 and rs10880 had a more discrete association (OR 3.537 95% CI 1.078-11.607, p = 0.037; OR 5.008, 95% CI 1.120-22.399, p = 0.035, respectively). CONCLUSIONS: Our study highlights the importance of studying LTBP4 polymorphisms associated with sarcopenia. These findings suggest that the rs1131620 polymorphism of the LTBP4 may be part of the observed sarcopenia process in patients with T2DM.

Influence of maternal obesity on the skeletal muscle of offspring.

Maternal obesity has been described as a clinical entity associated with an increased incidence of metabolic diseases in the offspring, indicating a fetal programming phenomenon during this critical development period. Fetal exposure to an obesogenic environment affects multiple organs and tissues, including skeletal muscle, which is particularly susceptible to stressors from the external environment. Several studies have described alterations in the morphology and composition of skeletal muscle tissue secondary to obesogenic exposure in utero. In addition, modifications in signaling pathways related to the metabolism of energy substrates have been found in children born to mothers with obesity during pregnancy. This review addresses the current evidence describing the consequences of fetal exposure to an obesogenic maternal diet on skeletal muscle tissue, focusing on changes in tissue composition, alterations in signaling pathways related to glucose and fatty acid metabolism, mitochondrial biogenesis, and oxidative phosphorylation.

La obesidad materna se ha descrito como una entidad clínica asociada con el aumento en la incidencia de enfermedades metabólicas en el producto de la gestación, lo que indica la existencia de un fenómeno de programación fetal que se lleva a cabo durante este periodo crítico del desarrollo. La exposición del feto a un ambiente obesogénico afecta múltiples órganos y tejidos, incluyendo el músculo esquelético, el cual es particularmente susceptible a estresores del ambiente externo. Diversos estudios han descrito alteraciones en la morfología y composición del tejido muscular esquelético secundarias a una exposición obesogénica in utero. Además, se han encontrado modificaciones en vías de señalización relacionadas al metabolismo de sustratos energéticos en los productos de madres con obesidad durante la gestación. En la presente revisión se aborda la evidencia actual que describe las consecuencias de la exposición fetal a una dieta materna obesogénica sobre el tejido muscular esquelético, con especial enfoque en los cambios en la composición del tejido, las alteraciones en las vías de señalización relacionadas con el metabolismo de la glucosa y los ácidos grasos, así como la biogénesis mitocondrial y la fosforilación oxidativa.

Influence of maternal obesity on the skeletal muscle of offspring / Influencia de la obesidad materna sobre el músculo esquelético de la progenie

Abstract Maternal obesity has been described as a clinical entity associated with an increased incidence of metabolic diseases in the offspring, indicating a fetal programming phenomenon during this critical development period. Fetal exposure to an obesogenic environment affects multiple organs and tissues, including skeletal muscle, which is particularly susceptible to stressors from the external environment. Several studies have described alterations in the morphology and composition of skeletal muscle tissue secondary to obesogenic exposure in utero. In addition, modifications in signaling pathways related to the metabolism of energy substrates have been found in children born to mothers with obesity during pregnancy. This review addresses the current evidence describing the consequences of fetal exposure to an obesogenic maternal diet on skeletal muscle tissue, focusing on changes in tissue composition, alterations in signaling pathways related to glucose and fatty acid metabolism, mitochondrial biogenesis, and oxidative phosphorylation.

Resumen La obesidad materna se ha descrito como una entidad clínica asociada con el aumento en la incidencia de enfermedades metabólicas en el producto de la gestación, lo que indica la existencia de un fenómeno de programación fetal que se lleva a cabo durante este periodo crítico del desarrollo. La exposición del feto a un ambiente obesogénico afecta múltiples órganos y tejidos, incluyendo el músculo esquelético, el cual es particularmente susceptible a estresores del ambiente externo. Diversos estudios han descrito alteraciones en la morfología y composición del tejido muscular esquelético secundarias a una exposición obesogénica in utero. Además, se han encontrado modificaciones en vías de señalización relacionadas al metabolismo de sustratos energéticos en los productos de madres con obesidad durante la gestación. En la presente revisión se aborda la evidencia actual que describe las consecuencias de la exposición fetal a una dieta materna obesogénica sobre el tejido muscular esquelético, con especial enfoque en los cambios en la composición del tejido, las alteraciones en las vías de señalización relacionadas con el metabolismo de la glucosa y los ácidos grasos, así como la biogénesis mitocondrial y la fosforilación oxidativa.

(-)-Epicatechin improves body composition of male rats descendant of obese mothers postnatally fed with a high-fat diet.

A combination of maternal obesity and high-fat diet (HFD) in offspring postnatal life has deleterious effects, and (-)-epicatechin (Epi) treatment can reverse these adverse effects. To investigate whether Epi administration can modify fat mass, muscle mass, and bone mass in male rats descended from obese mothers, fed postnatally on an HFD. Male offspring of mothers fed with control diet formed the control group (C), control group with high-fat diet (CHF), and control group with high-fat diet + epicatechin (CHF + Epi). Male offspring of maternal obesity formed the group with control diet (MO), maternal obesity group with high-fat diet (MOHF), and maternal obesity group with high-fat diet + epicatechin (MOHF + Epi). We measured total fat and weight of visceral adipose tissue by dissection and by dual-energy x-ray absorptiometry scanning body composition. Epicatechin diminished total and visceral pads fat of male offspring of CHF + Epi and MOHF + Epi groups versus to male offspring of CHF and MOHF groups. Besides, epicatechin increased lean mass in CHF + Epi and MOHF + Epi groups, but these changes were not significant. Total body mineral density of the male offspring of CHF, MOHF, and MOHF + Epi groups was significantly higher versus male offspring of C and MO groups. Obesity programming model plus a high-fat postnatal diet presents higher visceral adipose tissue, decreased lean mass, and modified body mineral density when compared with a direct obesity model and its controls. Epicatechin treatment improved body composition; however, it was not able to induce similar values as presented by the controls.

Leptin and its receptor are overexpressed in breast cancer tissue of postmenopausal Mexican-Mestizo women with obesity.

The aim of this study was to investigate the expression of leptin (LEP) and its receptor (LEPR) in breast cancer tissue of postmenopausal women with different body mass indexes (BMI), as well as the relationship of this expression with the rate of recurrence free survival (RFS). Leptin and LEPR expression, determined by immunohistochemistry, were studied in breast cancer tissues of 154 patients. Qualitative and semi-quantitative analysis of protein expression was performed by the H-Score method, through the ImageJ's IHC Profiler software. Kaplan-Meier survival analysis and log-rank statistic were used to estimate RFS differences. Protein expression of LEP, was significantly higher in women with overweight or with obesity, when compared to women with normal BMI (P = 0.032 and P = 0.013, respectively). We also observed a significantly higher expression of LEPR in breast tumor cells of women with obesity (58.8%), when compared to women with normal BMI (32.7%) (P = 0.007). Five-year survival rate, regarding LEPR expression, was 82.4% when positive and 94% when negative (P = 0.024). In the Cox proportional-hazards regression model, LEPR expression represented a risk factor for disease recurrence after adjustment for confounding factors (HR = 4.67; 95% CI: 1.13-19.31; P = 0.033). In conclusion, postmenopausal women with obesity and breast cancer present higher LEP and LEPR expression in breast tumors, when compared to women with normal BMI. Independently from BMI, women with tumors LEPR positive have worst RFS, when compared to women with tumors LEPR negative.

Increased FNDC5/IRISIN protein expression in breast cancer tissue is associated with obesity in postmenopausal women.

AIM: To analyse the fibronectin type III domain containing 5 (FNDC5)/irisin expression in tumour tissue of postmenopausal women presenting breast cancer and different body mass indexes (BMIs), proposing that obesity deregulates the expression of FNDC5/irisin at the breast tumour level. In addition, we investigated if different breast cancer cell lines are capable to synthesise this protein. METHODS: A total of 150 postmenopausal women (50 with a normal BMI, 50 presenting overweight and 50 having obesity) diagnosed with operable breast cancer were included. FNDC5/irisin expression was determined by immunohistochemistry or by immunocytochemistry. Qualitative analysis of protein expression was performed by the H-Score method, through ImageJ's IHC Profiler software. Statistical analyses were carried out using STATA V.14.0 (Texas, USA); p value<0.05 was accepted as statistically significant. Statistical power of the study was >80% with a p<0.05. RESULTS: FNDC5/irisin expression in breast cancer tissue of postmenopausal women with obesity was significantly increased when compared with FNDC5/irisin expression in women with a normal BMI (p=0.001). Furthermore, three breast cancer cell lines studied were capable to synthesise and express FNDC5/irisin, being the BT-474 cell line the one that exhibited the highest intensity of expression. CONCLUSIONS: Our results confirm that women with breast cancer and obesity exhibit an increased irisin expression in their tumorous tissue compared with women with breast cancer and normal BMI. Likewise, in vitro breast cancer cell lines have the capacity to synthesise and express FNDC5/irisin, without any extracellular stimuli, however the microenvironment surrounding these cells in vivo participates in its regulation.

Adiponectin and adiponectin receptor 1 expression proteins levels are modified in breast cancer in postmenopausal women with obesity.

AIM: To analyse the expression of adiponectin (ADIPOQ), and its receptors ADIPOR1 and ADIPOR2, in breast cancer tissue of postmenopausal women with different body mass indexes (BMIs). SUBJECTS AND METHODS: One hundred and fifty postmenopausal Mexican-Mestizo women with breast cancer were included. BMI was determined in each case. To carry out qualitative and semiquantitative assessments of protein expression by immunohistochemistry, the H-Score method was used, through ImageJ's IHC Profiler software. Statistical power of the study was >80% with a p<0.05. RESULTS: Fifty women had a normal BMI, 50 presented overweight and 50 had obesity. The expression of ADIPOQ in breast cancer tissue of postmenopausal woman with normal BMI was higher in comparison to women with overweight or with obesity (p=0.002 and p<0.001, respectively). Furthermore, the expression of ADIPOR1 in breast cancer tissue of postmenopausal women with normal BMI was significantly lower when compared with women with overweight or with obesity (p=0.005 and p<0.001, respectively). Meanwhile, the expression of ADIPOR2 in breast cancer tissue, in the cytoplasm, was similar in all groups studied. CONCLUSIONS: We found that women with overweight or obesity had a lower expression of ADIPOQ and a higher ADIPOR1 expression in breast cancer tissue, when compared with women with a normal BMI.

Different body mass indexes and their relation to prognosis of early-stage breast cancer in postmenopausal Mexican-Mestizo women.

It has been suggested that obesity increases the incidence of metastatic breast tumors, resulting in higher rates of recurrence, and increased mortality; for that reason, the aim of this study was to investigate if different body mass indexes modified the clinicopathologic characteristics of breast cancer; as well as, the recurrence-free survival in postmenopausal Mexican-Mestizo women. Two hundred twenty postmenopausal women with operable breast cancer were included. A structured questionnaire was applied to explore the existence of potential risk factors. Body mass index (BMI) was determined in each case and patients were grouped in accordance to their BMI in: normal weight, overweight, or obesity. Kaplan-Meier survival analysis and log-rank statistic were used to estimate recurrence-free-survival differences. Hormonal receptor(+)/HER2(-) was the most frequent breast cancer in all groups. Overweight women presented a statistically significant increased risk of this molecular subtype, with an odds ratio (OR) = 5.57; 95% confidence interval (CI) = 1.54-24.86; P = .004)). In addition, the triple-negative subtype was more frequent in women with a normal BMI in comparison to women with overweight (P = .016) or women with obesity. The heterogeneity in cancer subtypes regarding BMI was observed.

Bone mineral density and fractures in postmenopausal women of Maya-Mestizo ethnic origin with different body mass indexes.

BACKGROUND: Obesity protects against bone loss, but it increases the risk of fragility fractures. AIM: To determine if bone mineral density (BMD) and the prevalence of fractures are different in postmenopausal Maya-Mestizo women grouped according to their body mass index (BMI). SUBJECTS AND METHODS: We studied 600 postmenopausal Maya-Mestizo women. A structured questionnaire for risk factors was applied. Body mass index was determined. BMD was assessed at the lumbar spine and total hip by dual-energy X-ray absorptiometry. History of low trauma fracture was determined from medical records. ANOVA was used to compare mean BMD between women with different BMI. To compare the frequency of fractures according to BMI group, we used χ2 test. RESULTS: According to WHO classification of BMI, 16.3% of women had normal BMI, 35.3% were overweight, and 48.4% had obesity. We found that women with obesity had a higher BMD versus women with normal BMI or overweight in all the anatomical sites analysed. The prevalence of history of fractures was 18.2%. We did not find differences between the women of different BMI; the wrist was the most frequent skeletal site of the fracture. CONCLUSION: Obesity in postmenopausal Maya-Mestizo women is not a risk factor for developing fragility fractures.

Overweight and obesity in men with prostate cancer do not constitute risk factors for biochemical recurrence.

AIM: To investigate if overweight and obesity were associated with a higher degree of biochemical recurrence (BCR) after radical prostatectomy, in Mexican men with prostate cancer (PCa). METHODS: We included 180 men with PCa, who underwent radical prostatectomy (RP). Body mass index (BMI) was determined and the degree of PCa aggressiveness was established according to the D'Amico classification. Postoperative follow-up of all patients was performed with PSA quantification every/6 weeks after surgery and then at 3-month intervals for 1 year, followed every/6 months for 5 years. Postoperative BCR was defined as two consecutive increases in PSA levels ≥0.4 ng/mL, after RP. RESULTS: Sixty eight percent of the patients presented overweight or obesity. We found that only intermediate/high risk patients presented an increased risk factor for BCR-free survival (HR = 4.39; 95% CI = 1.74-11.24; p = 0.002). The median follow-up of all men has been 7.9 years and no significant differences in BCR-free survival time has been observed between the BMI groups. CONCLUSIONS: The overweight and obesity do not represent a risk factor to present BCR after RP for PCa. However, an intermediate/high risk, according to the D'Amico's classification, constitutes a risk factor to present BCR after radical prostatectomy, which is not related to the BMI.

(-)-Epicatechin reduces adiposity in male offspring of obese rats.

OBJECTIVE: To determine whether (-)-epicatechin (Epi) could decrease visceral adipose tissue and improve the metabolic profile of male offspring rats, after maternal obesity was induced by a high-fat diet (HFD). DESIGN: Maternal obesity in albino Wistar rats was induced with a HFD, whereas male offspring were fed with chow diet throughout the study. Eight male offspring per group, from different litters, were randomly assigned to the experimental or to the control groups. In the experimental group, Epi was administered at a dose of 1 mg/kg of body weight to the male offspring twice daily for two weeks, beginning at postnatal day (PND). MAIN MEASURES: Weight of visceral adipose tissue, adipocyte size, and several metabolic parameters. RESULTS: Epi administration in the male offspring induced a significant decrease in the amount of visceral fat (11.61 g less, P < 0.05) and in the size of adipose cells (28% smaller, P < 0.01). Besides, Epi was able to decrease insulin, leptin, and Homeostasis Model Assessment -Insulin Resistance (HOMA-IR) (P < 0.05), as well as triglycerides, when the experimental group was compared to the untreated male offspring of obese rats (P < 0.01). CONCLUSIONS: Epi administration can reverse the negative effects that maternal obesity has on the male offspring. This could be because Epi reduces the amount of visceral fat and improves metabolic profile.

WHOLE SEQUENCING OF THE MITOCHONDRIAL GENOME OF BREAST CANCER TISSUE IN MEXICAN-MESTIZO POSTMENOPAUSAL WOMEN WITH DIFFERENT BODY MASS INDEX.

BACKGROUND: Mitochondrial and oxidative stress has been related to obesity and breast cancer being this cancer more frequent and more aggressive in postmenopausal women with obesity. OBJECTIVE: The objective of this study was to investigate whether Mexican-Mestizo postmenopausal women with breast cancer and obesity present different somatic mutations in the mitochondrial DNA (mtDNA) when compared to women with normal body mass index (BMI). SUBJECTS AND METHODS: We included six Mexican-Mestizo postmenopausal women bearing breast cancer and who underwent mastectomy or breast-conserving surgery. BMI was determined in each case. Patients' genomic DNA was isolated from blood leukocytes and tumor tissue samples. Whole mtDNA sequence was determined by MitoChip v2.0 mitochondrial resequencing array, and data were analyzed using the GeneChip Sequence Analysis Software. Tumor mtDNA sequence was compared with matched leukocyte mtDNA sequence. RESULTS: Three women had a normal BMI and three presented obesity. Overall, we found 64 genetic variants: 53.1% were somatic mutations and 46.9% were polymorphisms; 44.1% were in the non-coding region and 55.9% were in genes that encode for mitochondrial proteins. Among the somatic mutations, 67.7% were in patients with normal BMI and 32.3% in patients with obesity. CONCLUSIONS: We did not find a higher frequency of mitochondrial somatic mutations in postmenopausal women with breast cancer and obesity compared to those with normal BMI. However, results could be due to the small number of women studied.

Whole sequencing of the mitochondrial genome of breast cancer tissue in Mexican-mestizo postmenopausal women with different body mass index

Abstract Background Mitochondrial and oxidative stress has been related to obesity and breast cancer being this cancer more frequent and more aggressive in postmenopausal women with obesity. Objective The objective of this study was to investigate whether Mexican-Mestizo postmenopausal women with breast cancer and obesity present different somatic mutations in the mitochondrial DNA (mtDNA) when compared to women with normal body mass index (BMI). Subjects and Methods We included six Mexican-Mestizo postmenopausal women bearing breast cancer and who underwent mastectomy or breast-conserving surgery. BMI was determined in each case. Patients’ genomic DNA was isolated from blood leukocytes and tumor tissue samples. Whole mtDNA sequence was determined by MitoChip v2.0 mitochondrial resequencing array, and data were analyzed using the GeneChip Sequence Analysis Software. Tumor mtDNA sequence was compared with matched leukocyte mtDNA sequence. Results Three women had a normal BMI and three presented obesity. Overall, we found 64 genetic variants: 53.1% were somatic mutations and 46.9% were polymorphisms; 44.1% were in the non-coding region and 55.9% were in genes that encode for mitochondrial proteins. Among the somatic mutations, 67.7% were in patients with normal BMI and 32.3% in patients with obesity. Conclusions We did not find a higher frequency of mitochondrial somatic mutations in postmenopausal women with breast cancer and obesity compared to those with normal BMI. However, results could be due to the small number of women studied.