Weight loss normalizes enhanced expression of the oncogene survivin in visceral adipose tissue and blood leukocytes from individuals with obesity.
体重减轻使肥胖个体内脏脂肪组织和血液白细胞中癌基因 survivin 的增强表达正常化。
- 作者列表："Izquierdo AG","Carreira MC","Rodriguez-Carnero G","Fernandez-Quintela A","Sueiro AM","Martinez-Olmos MA","Guzman G","De Luis D","Pinhel MAS","Nicoletti CF","Nonino CB","Ortega FJ","Portillo MP","Fernandez-Real JM","Casanueva FF","Crujeiras AB
BACKGROUND/OBJECTIVES:Survivin is an oncogene associated with a decrease in apoptosis, an increase in tumor growth, and poor clinical outcome of diverse malignancies. A correlation between obesity, cancer, and survivin is reported in the literature. To date, the impact of weight loss on change in survivin levels is understudied. This study was aimed at: (1) comparing survivin levels in adipose tissue (AT) from lean and obese animal models and evaluating changes after weight loss induced by energy restriction and/or exercise; (2) comparing survivin levels in normal weighted and obese humans and evaluating changes in survivin levels after weight loss induced by a very-low-calorie ketogenic diet (VLCKD) or bariatric surgery in AT and/or blood leukocytes (PBL/PBMCs). SUBJECTS/METHODS:Survivin expression was evaluated in subcutaneous (SAT) and visceral (VAT) AT derived from animal models of monogenic (Zucker rats) and diet-induced obesity (Sprague Dawley rats and C57BL/6J mice) and after a 4-week weight-loss protocol of energy restriction and/or exercise. Plasma was used to measure the inflammatory status. Survivin expression was also evaluated in PBMCs from patients with obesity and compared with normal weight, in PBLs after VLCKD, and in SAT and/or PBLs after bariatric surgery. RESULTS:Survivin expression was specifically higher in VAT from obese that lean animals, without differences in SAT. It decreased after weight loss induced by energy restriction and correlated with adiposity and inflammatory markers. In humans, the correlation between being obese and higher levels of survivin was confirmed. In obese subjects, survivin levels were reduced following weight loss after either VLCKD or bariatric surgery. Particularly, a decrease in PBMCs expression (not in SAT one) was found after surgery. CONCLUSIONS:Weight loss is effective in decreasing survivin levels. Also, PBL/PBMC should be regarded as appropriate mirror of survivin levels in VAT for the identification of an obesity-related protumoral microenvironment.
背景/目的: Survivin 是一种与细胞凋亡减少、肿瘤生长增加和各种恶性肿瘤临床预后差相关的癌基因。文献报道了肥胖、癌症和 survivin 之间的相关性。迄今为止，体重减轻对 survivin 水平变化的影响尚不清楚。本研究旨在 :( 1) 比较瘦和肥胖动物模型脂肪组织 (at) 中 survivin 水平，评价能量限制和/或运动诱导的体重减轻后的变化; (2)比较正常加权人和肥胖者的 survivin 水平，并评估极低热量生酮饮食 (VLCKD) 诱导的体重减轻后 survivin 水平的变化或 AT 和/或血白细胞 (PBL/PBMCs) 的减肥手术。 受试者/方法: 在来源于单基因动物模型 (Zucker 大鼠) 的皮下 (SAT) 和内脏 (VAT) 中评价 Survivin 的表达和饮食诱导的肥胖 (Sprague Dawley 大鼠和 C57BL/6J 小鼠) 以及 4 周的能量限制和/或运动减肥方案后。血浆用于测量炎症状态。还在肥胖患者的 pbmc 中评价了 Survivin 的表达，并与正常体重、 VLCKD 后的 PBLs 以及减肥手术后的 SAT 和/或 PBLs 进行了比较。 结果: Survivin 表达在肥胖的瘦动物的 VAT 中特异性较高，SAT 无差异。它在能量限制诱导的体重减轻后下降，并与肥胖和炎症标志物相关。在人类中，证实了肥胖与较高水平的 survivin 之间的相关性。在肥胖受试者中，VLCKD 或减肥手术后体重减轻后 survivin 水平降低。特别是术后 PBMCs 表达降低 (SAT one 中没有)。 结论: 体重减轻可有效降低 survivin 水平。同样，PBL/PBMC 应被视为 VAT 中 survivin 水平的合适镜像，用于识别肥胖相关的原瘤微环境。
METHODS:Maintaining adequate daily protein intake is important to maintain muscle mass throughout the lifespan. In this regard, the overnight period has been identified as a window of opportunity to increase protein intake in the elderly. However, it is unknown whether pre-sleep protein intake affects next-morning appetite and, consequently, protein intake. Therefore, the purpose of the current study was to investigate the effects of a pre-sleep protein drink on next-morning appetite, energy intake and metabolism. Twelve older individuals (eight males, four females; age: 71.3 ± 4.2 years) took part in a single-blind randomised cross-over study. After a standardised dinner, participants consumed either a 40-g protein drink, isocaloric maltodextrin drink, or placebo water control before bedtime. Next-morning appetite, energy intake, resting metabolic rate (RMR), respiratory exchange rate (RER), and plasma acylated ghrelin, leptin, glucose, and insulin concentrations were assessed. No between-group differences were observed for appetite and energy intake at breakfast. Furthermore, RMR, RER, and assessed blood markers were not significantly different between any of the treatment groups. Pre-sleep protein intake does not affect next-morning appetite and energy intake and is therefore a viable strategy to increase daily protein intake in an older population.
METHODS:Leptin (LEP) regulates glucose metabolism and energy storage in the body. Osteoarthritis (OA) is associated with the upregulation of serum LEP. LEP promoter methylation is associated with obesity. So far, few studies have explored the association of BMI and OA with LEP methylation. We assessed the interaction between body mass index (BMI) and OA on LEP promoter methylation. Data of 1114 participants comprising 583 men and 558 women, aged 30−70 years were retrieved from the Taiwan Biobank Database (2008−2015). Osteoarthritis was self-reported and cases were those who reported having ever been clinically diagnosed with osteoarthritis. BMI was categorized into underweight, normal weight, overweight, and obesity. The mean LEP promoter methylation level in individuals with osteoarthritis was 0.5509 ± 0.00437 and 0.5375 ± 0.00101 in those without osteoarthritis. The interaction between osteoarthritis and BMI on LEP promoter methylation was significant (p-value = 0.0180). With normal BMI as the reference, the mean LEP promoter methylation level was significantly higher in obese osteoarthritic individuals (β = 0.03696, p-value = 0.0187). However, there was no significant association between BMI and LEP promoter methylation in individuals without osteoarthritis, regardless of BMI. In conclusion, only obesity was significantly associated with LEP promoter methylation (higher levels) specifically in osteoarthritic patients.
METHODS:Background For the same BMI, South Asians have a higher body fat percentage, a higher liver fat content and a more adverse metabolic profile than whites. South Asians may have a lower fat oxidation than whites, which could result in an unfavorable metabolic profile when exposed to increased high-fat foods consumption and decreased physical activity as in current modern lifestyle. Objective To determine substrate partitioning, liver fat accumulation and metabolic profile in South Asian and white men in response to overfeeding with high-fat diet under sedentary conditions in a respiration chamber. Design Ten South Asian men (BMI, 18–29 kg/m^2) and 10 white men (BMI, 22–33 kg/m^2), matched for body fat percentage, aged 20–40 year were included. A weight maintenance diet (30% fat, 55% carbohydrate, and 15% protein) was given for 3 days. Thereafter, a baseline measurement of liver fat content (1H-MRS) and blood parameters was performed. Subsequently, subjects were overfed (150% energy requirement) with a high-fat diet (60% fat, 25% carbohydrate, and 15% protein) over 3 consecutive days while staying in a respiration chamber mimicking a sedentary lifestyle. Energy expenditure and substrate use were measured for 3 × 24-h. Liver fat and blood parameters were measured again after the subjects left the chamber. Results The 24-h fat oxidation as a percentage of total energy expenditure did not differ between ethnicities ( P = 0.30). Overfeeding increased liver fat content ( P = 0.02), but the increase did not differ between ethnicities ( P = 0.64). In South Asians, overfeeding tended to increase LDL-cholesterol ( P = 0.08), tended to decrease glucose clearance ( P = 0.06) and tended to elevate insulin response ( P = 0.07) slightly more than whites. Conclusions Despite a similar substrate partitioning and similar accretion of liver fat, overfeeding with high-fat under sedentary conditions tended to have more adverse effects on the lipid profile and insulin sensitivity in South Asians.