(-)-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.

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.

Complete sequence of the ANKK1 gene in Mexican-Mestizo individuals with obesity, with or without binge eating disorder.

BACKGROUND: The aim of this study was to investigate if Mexican-Mestizo individuals with obesity, with or without binge eating disorder (BED), exhibited mutations or other type of genetic variants in the sequence of ANKK1. SUBJECTS AND METHODS: Fifty unrelated individuals (21-53 years of age) with obesity, of Mexican-Mestizo ethnic origin were included; 25 of them had BED and 25 presented obesity without BED. The diagnosis of BED was based on criteria proposed in the Diagnostic and Statistical Manual of Mental Disorders (DSM-5). Besides, we also analyzed 100 individuals with normal body mass index. DNA from blood leukocytes was amplified by the polymerase chain reaction and all exons of ANKK1 were sequenced. RESULTS: After ANKK1 sequencing we did not find any mutations; however, we observed various polymorphisms. One polymorphism, rs4938013 in exon 2 showed an association with obesity, whilst rs1800497 (also known as Taq1A) in exon 8, showed an association with BED (P = 0.020). Remarkable, for this study, the number of individuals for both polymorphisms for and additive model was sufficient to derive strong statistical power (80%, with a P < 0.05). CONCLUSIONS: To our knowledge, this constitutes the first report where the complete sequences of ANKK1 has been analyzed in individuals with obesity, with or without BED. No mutations were found; however, one polymorphism was associated with obesity, with or without BED, and another one was associated with BED.

PPARGC1A and ADIPOQ polymorphisms are associated with aggressive prostate cancer in Mexican-Mestizo men with overweight or obesity.

BACKGROUND: Obesity constitutes a risk factor for the development of aggressive forms of prostate cancer. It has been proposed, that prostate cancer has a genetic predisposition and that PPARGC1A and ADIPOQ polymorphisms play a role in the development of this condition. OBJECTIVE: To analyse the association of two PPARGC1A and ADIPOQ polymorphisms as well as their haplotypes, with the development of aggressive prostate cancer in Mexican-Mestizo men with overweight or obesity. SUBJECTS AND METHODS: Two hundred fifty seven men with prostate cancer of Mexican-Mestizo origin were included. Body mass index (BMI) was determined and the degree of prostate cancer aggressiveness by the D'Amico classification. DNA was obtained. Rs7665116 and rs2970870 of PPARGC1A, and rs266729 and rs1501299 of ADIPOQ were studied by real-time PCR allelic discrimination. Pairwise linkage disequilibrium, between single nucleotide polymorphisms was calculated and haplotype analysis was performed. RESULTS: A higher-risk (D'Amico classification) was observed in 21.8% of patients. An association of cancer aggressiveness with rs2970870 of PPARGC1A, and rs501299 of ADIPOQ, as well as with one haplotype of ADIPOQ was documented. CONCLUSIONS: This is the first study regarding the relationship of PPARGC1A and ADIPOQ polymorphisms, and the aggressiveness of prostate cancer in men with overweight or obesity.

Association of a TFAM haplotype with aggressive prostate cancer in overweight or obese Mexican Mestizo men.

BACKGROUND: Mitochondrial dysfunction has been associated with the development of cancer and obesity, being prostate cancer more aggressive in obese men. It has been suggested that the mitochondrial transcription factor A (TFAM) plays a central role in these events. OBJECTIVE: The aim of this study was to analyze the possible association of 3 TFAM polymorphisms, as well as their haplotypes, with the development of aggressive prostate cancer in overweight or obese Mexican Mestizo men. SUBJECTS AND METHODS: A total of 257 unrelated men with histologically confirmed prostate cancer, of Mexican Mestizo ethnic origin, were included. Body mass index was determined and the degree of prostate cancer aggressiveness was demarcated by the D'Amico classification. DNA was obtained from blood leukocytes. The rs1937, rs1049432, and rs11006132, as well as their haplotypes, were studied by real-time polymerase chain reaction allelic discrimination. Deviations from Hardy-Weinberg equilibrium were tested. Pairwise linkage disequilibrium between single nucleotide polymorphisms was calculated; haplotype analysis was performed. RESULTS: A higher risk (D'Amico classification) was documented in 56 patients (21.8%). We did not find a significant association among those polymorphisms analyzed; however, one haplotype was significantly associated with cancer aggressiveness. CONCLUSIONS: To our knowledge, this constitutes the first study regarding the relationship of 3 TFAM polymorphisms, as well as their haplotypes, and the aggressiveness of prostate cancer in overweight or obese men; the most frequent haplotype was associated with cancer aggressiveness.

Genetic variants in ATP6 and ND3 mitochondrial genes are not associated with aggressive prostate cancer in Mexican-Mestizo men with overweight or obesity.

Mitochondrial defects have been related to obesity and prostate cancer. We investigated if Mexican-Mestizo men presenting this type of cancer, exhibited somatic mutations of ATP6 and/or ND3.Body mass index (BMI) was determined; the degree of prostate cancer aggressiveness was demarcated by the Gleason score. DNA from tumor tissue and from blood leukocytes was amplified by the polymerase chain reaction and ATP6 and ND3 were sequenced. We included 77 men: 20 had normal BMI, 38 were overweight and 19 had obesity; ages ranged from 52 to 83. After sequencing ATP6 and ND3, from DNA obtained from leukocytes and tumor tissue, we did not find any somatic mutations. All changes observed, in both genes, were polymorphisms. In ATP6 we identified, in six patients, two non-synonymous nucleotide changes and in ND3 we observed that twelve patients presented non-synonymous polymorphisms. To our knowledge, this constitutes the first report where the complete sequences of the ATP6 and ND3 have been analyzed in Mexican-Mestizo men with prostate cancer and diverse BMI. Our results differ with those reported in Caucasian populations, possibly due to ethnic differences.