The Impact of Gastric Bypass on Telomere Length and Shelterin Complex Gene Expression: 6 Months Prospective Study.

BACKGROUND: Telomeres are structures located at the ends of chromosomes associated with a protein complex, known as the shelterin complex. In individuals with obesity, excess adipose tissue plays a key role in inducing a chronic and systemic inflammatory state, which can cause TL shortening. In this context, bariatric surgery is one of the most effective treatment modalities in improving metabolic control. AIM: Therefore, the present study aimed to evaluate how a short postoperative period of gastric bypass affects TL and expression of POT1, TRF1 and TRF2 genes. METHODS: Forty-eight women submitted to RYGB were evaluated before and after 6 months of the surgical procedure. Anthropometric measures of body weight and height (BMI), abdominal circumference (AC), body composition, food intake and blood collection for biochemical evaluation, TL analysis (DNA), and gene expression (RNA) were collected at each moment. RESULTS: There was a reduction of weight, BMI, AC, FM and FFM as well as of glycemia, total cholesterol, LDL-cholesterol, and triglycerides after gastric bypass. No difference in energy intake and macronutrients consumption was observed. There was no significant change in TL, but there was a significant increase of POT1 and TRF1 gene expression after surgery, while TRF2 expression did not change. CONCLUSIONS: Despite bariatric surgery is not capable of increasing telomere length in a short-term period, no reduction is observed; additionally, we found a correlation between serum triglycerides concentration and TL. The increase of POT1 and TRF1 gene expression may explain the maintenance of the TL after 6 months postoperative period.

Green tea supplementation improves oxidative stress biomarkers and modulates IL-6 circulating levels in obese women.

INTRODUCTION: Introduction: obesity is associated with high levels of oxidative stress (OS) and inflammation. There is a lot of evidence that some polyphenols, such as green tea, have a positive impact on the OS state and consecutively, on inflammation. Objectives: the purposes of this study were: a) evaluate OS biomarkers in both obese and normal weight women; and b) evaluate if green tea supplementation has an impact on OS and inflammatory cytokine biomarkers of obese women. Methods: we evaluated obese (body mass index [BMI] ≥ 40 kg/m²) and normal weight (BMI between 18.5 and 24.9 kg/m²) women. Blood samples were used to access malondialdehyde (MDA), trolox equivalent antioxidant capacity (TEAC) and inflammatory cytokines. We randomly chose obese patients (18 individuals) and then gave them green tea supplementation for eight weeks. Statistical analysis included the Shapiro-Wilk, Wilcoxon, independent and paired t tests; p < 0.05 were considered as significant. Results: we enrolled 42 obese (BMI: 48.2 ± 9.3kg/m2) and 21 normal weight (BMI: 22.5 ± 2 kg/m2) women with an average age of 36.2 ± 9.1 years old. The serum levels of MDA were higher in obese (2.52 ± 0.31 µmol/l) than in eutrophic women (2.13 ± 0.26 µmol/l; p = 0.000). On the other hand, lower TEAC values were observed in the obese (0.75 ± 0.06 mM/l) than in the eutrophic group (0.78 ± 0.04 mM/l; p = 0.009). After the green tea intervention, MDA decreased 4.7% and TEAC increased 10%. Interleukin-6 (IL-6) serum levels decreased 12.7% after treatment (p = 0.03). Conclusions: a) the obese group had lower antioxidant capacity than eutrophic; and b) green tea supplementation ameliorated TEAC and MDA and reduced serum levels of IL-6 in obese women.

INTRODUCCIÓN: Introducción: la obesidad se asocia con altos niveles de estrés oxidativo (EO) e inflamación. Existe mucha evidencia de que algunos polifenoles, como el té verde, tienen un impacto positivo en el estado del EO y, consecutivamente, en la inflamación. Objetivos: los propósitos de este estudio fueron: a) evaluar los biomarcadores de EO en mujeres obesas y de peso normal; y b) evaluar si la suplementación con té verde tiene un impacto en el EO y biomarcadores de citoquinas inflamatorias de las mujeres obesas. Métodos: evaluamos mujeres obesas (índice de masa corporal [IMC] ≥ 40 kg/m²) y con peso normal (IMC entre 18,5 y 24,9 kg/m²). Se utilizaron muestras de sangre para determinar el malondialdehído (MDA), la capacidad antioxidante equivalente de trolox (TEAC) y las citoquinas inflamatorias. Elegimos al azar pacientes obesas (18 individuos) y luego les dimos suplementos de té verde durante ocho semanas. El análisis estadístico incluyó las pruebas de Shapiro-Wilk, Wilcoxon, t pareadas e independientes; p < 0,05 fueron considerados como significativos. Resultados: se reclutaron 42 mujeres obesas (IMC: 48,2 ± 9,3 kg/m2) y 21 de peso normal (IMC: 22,5 ± 2 kg/m2) con un promedio de edad de 36,2 ± 9,1 años. Los niveles séricos de MDA fueron más altos en las personas obesas (2,52 ± 0,31 µmol/L) que en las mujeres eutróficas (2,13 ± 0,26 µmol/L; p = 0,000). Por otro lado, se observaron valores TEAC más bajos en los obesos (0,75 ± 0,06 mM/L) que en el grupo eutrófico (0,78 ± 0,04 mM/L; p = 0,009). Después de la intervención con té verde, la MDA disminuyó 4.7% y el TEAC aumentó 10%. Los niveles séricos de interleucina-6 (IL-6) disminuyeron 12.7% después del tratamiento (p = 0,03). Conclusiones: a) mujeres obesas tienen menor capacidad antioxidante que las eutrófica; y b) la suplementación con té verde mejora TEAC y MDA y redujo los niveles séricos de IL-6 en mujeres obesas.

Impact of green tea epigallocatechin-3-gallate on HIF1-α and mTORC2 expression in obese women: anti-cancer and anti-obesity effects? / Impacto del té verde epigalocatequina-3-galato en la expresión de HF1-a y mTORC2 en mujeres obesas: ¿efectos anticancerígenos y antiobesidad?

Introduction: epigallocatechin-3-gallate (EGCG) is the most abundant catechin contained in green tea (Camellia sinensis) and has been associated with anti-obesity and anti-cancer effects, but the exact molecular mechanisms remain elusive. In this context, this study was designed to improve the understanding of the EGCG anti-obesity and anti-cancer action. Objectives: this study was designed to examine the effects of EGCG on the expression of genes involved in obesity and cancer pathways in the peripheral blood mononuclear cells of obese women. Material and methods: this longitudinal interventional study enrolled eleven women with severe obesity that were submitted to eight weeks of green tea (decaffeinated green tea capsules with 450.7 mg of EGCG, two capsules/day) supplementation (intervention group) and ten eutrophic women as a control group. Weight (kg), body mass index (BMI, kg/m2), fat mass (kg) and gene expression (qPCR method) were assessed before and after supplementation. HIF1-alpha (HIF1-α), phosphoinositide-3-kinase regulatory subunit 1 (PIK3R1) and rapamycin-insensitive companion of mTOR (RICTOR) were selected as potential targets. Results: after supplementation, body weight (114.9 ± 14.3 versus 115 ± 13.8 kg), body mass index (44.1 ± 3.7 versus 44.1 ± 3.9 kg/m2) and fat mass (47.6 ± 3.3 versus 47.3 ± 3.4 kg) did not change. EGCG upregulated the RICTOR and HIF1-α expression, however, did not modify PI3K expression. Conclusion: this study demonstrated that EGCG has a potential role to obesity and cancer related to obesity control and can be used not only for the purpose of weight loss, but also for the improvement of obesity-related comorbidities

Introducción: la obesidad se asocia con altos niveles de estrés oxidativo (EO) e inflamación. Existe mucha evidencia de que algunos polifenoles, como el té verde, tienen un impacto positivo en el estado del sistema operativo y consecutivamente en la inflamación. Objetivos: los propósitos de este estudio fueron: a) acceso a biomarcadores de EO en mujeres obesas y de peso normal; y b) evaluar si la suplementación con té verde tiene impacto en los biomarcadores de citoquinas inflamatorias y de EO de mujeres obesas. Métodos: evaluamos mujeres obesas (índice de masa corporal - IMC ≥ 40 kg/m²) y peso normal (IMC entre 18,5 y 24,9 kg/m²). Se utilizaron muestras de sangre para acceder al malondialdehído (MDA), la capacidad antioxidante equivalente de Trolox (TEAC) y las citoquinas inflamatorias. Elegimos al azar pacientes obesos (18 individuos) y luego les dimos suplementos de té verde durante 8 semanas. El análisis estadístico incluyó las pruebas de Shapiro-Wilk, Wilcoxon, t pareadas e independientes, p < 0,05 se consideraron significativas. Resultados: se reclutaron 42 mujeres obesas (IMC: 48,2 ± 9,3 kg/m2) y 21 de peso normal (IMC: 22,5 ± 2 kg/m2) con una edad promedio de 36,2 ± 9,1 años. Los niveles séricos de MDA fueron más altos en las personas obesas (2,52 ± 0,31 μmol/L) que en las mujeres eutróficas (2,13 ± 0,26 μmol/L; p = 0.000). Por otro lado, se observaron valores de TEAC más bajos en obesos (0,75 ± 0,06 mM) que en el grupo eutrófico (0,78 ± 0,04 mM; p = 0,009). Después de la intervención del té verde, la MDA disminuyó 4,7% y el TEAC aumentó 10%. Los niveles séricos de interleucina-6 (IL-6) disminuyeron 12,7% después del tratamiento (p = 0,03). Conclusiones: el grupo obeso tenía menor capacidad antioxidante que el eutrófico. La suplementación con té verde mejoró TEAC y MDA y redujo los niveles séricos de IL-6 en mujeres obesas

Impact of green tea epigallocatechin-3-gallate on HIF1-α and mTORC2 expression in obese women: anti-cancer and anti-obesity effects?

INTRODUCTION: Introduction: epigallocatechin-3-gallate (EGCG) is the most abundant catechin contained in green tea (Camellia sinensis) and has been associated with anti-obesity and anti-cancer effects, but the exact molecular mechanisms remain elusive. In this context, this study was designed to improve the understanding of the EGCG anti-obesity and anti-cancer action. Objectives: this study was designed to examine the effects of EGCG on the expression of genes involved in obesity and cancer pathways in the peripheral blood mononuclear cells of obese women. Material and methods: this longitudinal interventional study enrolled eleven women with severe obesity that were submitted to eight weeks of green tea (decaffeinated green tea capsules with 450.7 mg of EGCG, two capsules/day) supplementation (intervention group) and ten eutrophic women as a control group. Weight (kg), body mass index (BMI, kg/m2), fat mass (kg) and gene expression (qPCR method) were assessed before and after supplementation. HIF1-alpha (HIF1-α), phosphoinositide-3-kinase regulatory subunit 1 (PIK3R1) and rapamycin-insensitive companion of mTOR (RICTOR) were selected as potential targets. Results: after supplementation, body weight (114.9 ± 14.3 versus 115 ± 13.8 kg), body mass index (44.1 ± 3.7 versus 44.1 ± 3.9 kg/m2) and fat mass (47.6 ± 3.3 versus 47.3 ± 3.4 kg) did not change. EGCG upregulated the RICTOR and HIF1-α expression, however, did not modify PI3K expression. Conclusion: this study demonstrated that EGCG has a potential role to obesity and cancer related to obesity control and can be used not only for the purpose of weight loss, but also for the improvement of obesity-related comorbidities.

INTRODUCCIÓN: Introducción: la obesidad se asocia con altos niveles de estrés oxidativo (EO) e inflamación. Existe mucha evidencia de que algunos polifenoles, como el té verde, tienen un impacto positivo en el estado del sistema operativo y consecutivamente en la inflamación. Objetivos: los propósitos de este estudio fueron: a) acceso a biomarcadores de EO en mujeres obesas y de peso normal; y b) evaluar si la suplementación con té verde tiene impacto en los biomarcadores de citoquinas inflamatorias y de EO de mujeres obesas. Métodos: evaluamos mujeres obesas (índice de masa corporal - IMC ≥ 40 kg/m²) y peso normal (IMC entre 18,5 y 24,9 kg/m²). Se utilizaron muestras de sangre para acceder al malondialdehído (MDA), la capacidad antioxidante equivalente de Trolox (TEAC) y las citoquinas inflamatorias. Elegimos al azar pacientes obesos (18 individuos) y luego les dimos suplementos de té verde durante 8 semanas. El análisis estadístico incluyó las pruebas de Shapiro-Wilk, Wilcoxon, t pareadas e independientes, p < 0,05 se consideraron significativas. Resultados: se reclutaron 42 mujeres obesas (IMC: 48,2 ± 9,3 kg/m2) y 21 de peso normal (IMC: 22,5 ± 2 kg/m2) con una edad promedio de 36,2 ± 9,1 años. Los niveles séricos de MDA fueron más altos en las personas obesas (2,52 ± 0,31 µmol/L) que en las mujeres eutróficas (2,13 ± 0,26 µmol/L; p = 0.000). Por otro lado, se observaron valores de TEAC más bajos en obesos (0,75 ± 0,06 mM) que en el grupo eutrófico (0,78 ± 0,04 mM; p = 0,009). Después de la intervención del té verde, la MDA disminuyó 4,7% y el TEAC aumentó 10%. Los niveles séricos de interleucina-6 (IL-6) disminuyeron 12,7% después del tratamiento (p = 0,03). Conclusiones: el grupo obeso tenía menor capacidad antioxidante que el eutrófico. La suplementación con té verde mejoró TEAC y MDA y redujo los niveles séricos de IL-6 en mujeres obesas.

Trans-chalcone increases p53 activity via DNAJB1/HSP40 induction and CRM1 inhibition.

Naturally-occurring chalcones and synthetic chalcone analogues have been demonstrated to have many biological effects, including anti-inflammatory, anti-malarial, anti-fungal, and anti-oxidant/anti-cancerous activities. Compared to other chalcones, trans-chalcone exhibits superior inhibitory activity in cancer cell growth as shown via in vitro assays, and exerts anti-cancerous effects via the activation of the p53 tumor suppressor protein. Thus, characterization of the specific mechanisms, by which trans-chalcone activates p53, can aid development of new chemotherapeutic drugs that can be used individually or synergistically with other drugs. In this report, we found that trans-chalcone modulates many p53 target genes, HSP40 being the most induced gene in the RNA-Seq data using trans-chalcone-treated cells. CRM1 is also inhibited by trans-chalcone, resulting in the accumulation of p53 and other tumor suppressor proteins in the nucleus. Similar effects were seen using trans-chalcone derivatives. Overall, trans-chalcone could provide a strong foundation for the development of chalcone-based anti-cancer drugs.

Green tea supplementation promotes leukocyte telomere length elongation in obese women.

INTRODUCTION: inflammation and oxidative stress are factors that may play a substantial role in telomere attrition. In line of this, obesity is associated with telomere shortening. Green tea had anti-inflammatory and antioxidant effects and may alter telomere length (TL). OBJECTIVES: we evaluated the effect of decaffeinated green tea supplementation in obese women on TL. METHODS: we conducted a cross-sectional interventional study with ten obese (body mass index [BMI] > 40 kg/m²) and eight normal weight (BMI > 18.5 and < 24.9 kg/m²) women (age between 27 and 48 years). The supplementation was carried out with capsules (each contained 450.7 mg of epigallocatechin-3-gallate) during eight weeks. Anthropometric and dietary intake assessment, and blood collection (for biochemical and TL analysis by quantitative PCR) were performed before and after supplementation. Normal weight patients were evaluated at a single moment. RESULTS: we observed a significant increase on TL after supplementation (1.57 ± 1.1 to 3.2 ± 2.1 T/Sratio; p < 0.05). Moreover, we found shorter TL in obese patients (day 0) when compared to normal weight individuals (3.2 ± 1.9 T/Sratio; p < 0.05) and an inverse association between TL and BMI, even after age adjustment (beta = -0.527; r² = 0.286; IC = -0.129, -0.009). CONCLUSION: obesity is related to shorter telomeres. Green tea supplementation during eight weeks promotes telomere elongation in obese women.

The Curcumin Analog CH-5 Exerts Anticancer Effects in Human Osteosarcoma Cells via Modulation of Transcription Factors p53/Sp1.

Curcumin is a potential anticancer drug with poor bioavailability, which limits its clinical use as a therapeutic agent. The aim of this study was a preliminary evaluation of the curcumin analogue CH-5 as a cytotoxic agent in human osteosarcoma cell lines U2OS, MG-63, and Saos-2. CH-5 inhibited cell viability at lower concentrations than curcumin, leading to the induction of apoptosis. The cellular levels of the transcription factors p53 and Sp1 affect the expression of cellular pathways that lead to apoptosis. CH-5 increased p53 protein levels in U2OS cells and reduced Sp1 levels, with a consequent effect on the expression of their target genes DNA methyltransferase 1 (DNMT1) and growth arrest and DNA damage-inducible 45 alpha gene (Gadd45a). CH-5 repressed DNMT1 and increased Gadd45a mRNA expression, which was dependent on p53, as this effect was only observed in the colorectal cancer cell line HCT116 with active p53, but not in the isogenic p53-deficient HCT116 cells. CH-5 also reduced the protein levels of DNMT1, which led to the upregulation of Gadd45a. These results suggest that CH-5 has potentially higher anticancer activity than curcumin, which is associated with the expression of apoptosis-associated genes regulated by the transcription factors Sp1 and p53. Future work on CH-5 will define the therapeutic potential of this compound in vivo.

Changes in Global Transcriptional Profiling of Women Following Obesity Surgery Bypass.

BACKGROUND: Differential gene expression in peripheral blood mononuclear cells (PBMCs) after Roux-en-Y gastric bypass (RYGB) is poorly characterized. Markers of these processes may provide a deeper understanding of the mechanisms that underlie these events. The main goal of this study was to identify changes in PBMC gene expression in women with obesity before and 6 months after RYGB-induced weight loss. METHODS: The ribonucleic acid (RNA) of PBMCs from 13 obese women was analyzed before and 6 months after RYGB; the RNA of PBMCs from nine healthy women served as control. The gene expression levels were determined by microarray analysis. Significant differences in gene expression were validated by real-time quantitative polymerase chain reaction (RT-qPCR). RESULTS: Microarray analysis for comparison of the pre- and postoperative periods showed that 1366 genes were differentially expressed genes (DEGs). The main pathways were related to gene transcription; lipid, energy, and glycide metabolism; inflammatory and immunological response; cell differentiation; oxidative stress regulation; response to endogenous and exogenous stimuli; substrate oxidation; mTOR signaling pathway; interferon signaling; mitogen-activated protein kinases (MAPK), cAMP response element binding protein (CREB1), heat shock factor 1 (HSF1), and sterol regulatory element binding protein 1c (SREBP-1c) gene expression; adipocyte differentiation; and methylation. CONCLUSIONS: Six months after bariatric surgery and significant weight loss, many molecular pathways involved in obesity and metabolic diseases change. These findings are an important tool to identify potential targets for therapeutic intervention and clinical practice of nutritional genomics in obesity.