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1.
Levels of Circulating miR-122 are Associated with Weight Loss and Metabolic Syndrome.
Hess, AL, Larsen, LH, Udesen, PB, Sanz, Y, Larsen, TM, Dalgaard, LT
Obesity (Silver Spring, Md.). 2020;(3):493-501
Abstract
OBJECTIVE This study investigated whether the levels of specific serum microRNAs (miRNAs) were altered following diet-induced weight loss and whether the serum miRNAs differed in the presence of the metabolic syndrome. METHODS The study was a weight loss intervention trial with a prescribed energy deficit of approximately 500 kcal/d. Levels of 22 miRNAs were determined in serum samples from 85 participants with overweight or obesity. miRNAs were analyzed using TaqMan Array miRNA Cards and normalized to the geometric mean of spiked-in ath-miR-159a and U6 small nuclear RNA using the ΔCT method. RESULTS The average weight loss was 5.7 kg (P < 0.001). miR-122-5p (-0.18 ± 0.06 log fold relative to initial, P < 0.01) and miR-193a-5p (-0.12 ± 0.04, P < 0.01) levels decreased in response to weight loss. miR-126a-3p (0.11 ± 0.04, P = 0.01) and miR-222-3p (1.51 ± 0.12, P < 0.001) levels increased. Furthermore, a higher level of miR-122-5p was observed at baseline in participants with the metabolic syndrome compared with participants without (0.28 ± 0.08, P < 0.01). CONCLUSIONS Changes in circulating miR-122-5p, miR-126a-3p, miR-193a-5p, and miR-222-3p in response to diet-induced weight loss are demonstrated. Furthermore, assessment of miR-122-5p could be an indicator of an adverse metabolic health status independent of obesity.
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2.
A Single Motivational Lecture Can Promote Modest Weight Loss: A Randomized Controlled Trial.
Nakata, Y, Sasai, H, Tsujimoto, T, Hashimoto, K, Kobayashi, H
Obesity facts. 2020;(2):267-278
Abstract
BACKGROUND Obesity is a public health problem worldwide. To widely disseminate weight-loss interventions across the target population, a cost-effective approach is needed. OBJECTIVE We aimed to test whether a single motivational lecture could promote weight loss. METHODS Our study was a 3-month randomized controlled trial, and we recruited participants via local newspaper advertisements in 3 cities in Ibaraki Prefecture, Japan, and randomly assigned them to a control group (no intervention) and an intervention group, who attended a single motivational lecture lasting approximately 2 h. No other lectures or textbooks were provided. The eligibility criteria included an age of 40-64 years, a body mass index (BMI) of 25-40 kg/m2, and the presence of at least 1 component of metabolic syndrome. The primary outcome was body weight change at 3 months. RESULTS We enrolled 145 eligible participants with a mean age of 53.8 ± 7.1 years and a BMI of 28.5 ± 3.1 kg/m2. The 3-month body weight change in the control and intervention groups was -0.65 kg (95% confidence interval [CI] -1.09 to -0.20) and -2.48 kg (95% CI -3.01 to -1.95), respectively. The between-group difference was 1.83 kg (95% CI 1.15-2.51). CONCLUSIONS The significant difference suggested that a single motivational lecture is an effective option to promote modest weight loss in the short term.
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3.
DNA methylation markers in obesity, metabolic syndrome, and weight loss.
Samblas, M, Milagro, FI, Martínez, A
Epigenetics. 2019;(5):421-444
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Abstract
The fact that not all individuals exposed to the same environmental risk factors develop obesity supports the hypothesis of the existence of underlying genetic and epigenetic elements. There is suggestive evidence that environmental stimuli, such as dietary pattern, particularly during pregnancy and early life, but also in adult life, can induce changes in DNA methylation predisposing to obesity and related comorbidities. In this context, the DNA methylation marks of each individual have emerged not only as a promising tool for the prediction, screening, diagnosis, and prognosis of obesity and metabolic syndrome features, but also for the improvement of weight loss therapies in the context of precision nutrition. The main objectives in this field are to understand the mechanisms involved in transgenerational epigenetic inheritance, and featuring the nutritional and lifestyle factors implicated in the epigenetic modifications. Likewise, DNA methylation modulation caused by diet and environment may be a target for newer therapeutic strategies concerning the prevention and treatment of metabolic diseases.
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Evaluations of Lifestyle, Dietary, and Pharmacologic Treatments for Pediatric Nonalcoholic Fatty Liver Disease: A Systematic Review.
Mann, JP, Tang, GY, Nobili, V, Armstrong, MJ
Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association. 2019;(8):1457-1476.e7
Abstract
BACKGROUND & AIMS There are no approved treatments for pediatric nonalcoholic fatty liver disease (NAFLD) and there is a lack of consensus on the best outcome measure for randomized controlled trials. We performed a systematic review of treatments tested for pediatric NAFLD, the degree of heterogeneity in trial design, and endpoints analyzed in these studies. METHODS We searched publication databases and clinical trial registries through January 7, 2018 for randomized controlled trials (published and underway) of children (<18 years) with NAFLD. We assessed improvements in histologic features, radiologic and biochemical markers of reduced fibrosis, metabolic syndrome parameters, and adverse events. The quality of the trials was assessed using a modified version of the Cochrane risk of bias tool. RESULTS Our final analysis included 21 randomized controlled trials, comprising 1307 participants (mean age, 12.6 years; 63% male; mean duration of intervention, 8 months). Most studies evaluated weight loss with lifestyle intervention (n=8), oral polyunsaturated fatty acid treatment (PUFAs, n=6), or oral antioxidant treatment (n=7). Biomarkers of NAFLD decreased with weight loss, but most studies did not include histologic data. Trials of antioxidants were heterogeneous; some reported reduced histologic features of steatohepatitis with no effect on triglycerides or insulin resistance. PUFAs and probiotics reduced radiologic markers of steatosis, insulin resistance, and levels of triglycerides. Only 38% of the trials had biopsy-proven NAFLD as an inclusion criterion. There was heterogeneity in trial primary endpoints; 10 studies (48%) used levels of aminotransferases or ultrasonography findings as a primary endpoint and only 3 trials (14%) used histologic features as the primary endpoint. We identified 13 randomized controlled trials that are underway in children with NAFLD. None of the protocols include collection of liver biopsies; 9 trials (69%) will use magnetic resonance imaging quantification of steatosis as a primary outcome. CONCLUSIONS In a systematic review of published and active randomized controlled trials of children with NAFLD, we found a large amount of heterogeneity in study endpoints and inclusion criteria. Few trials included histologic analyses. Antioxidants appear to reduce some features of steatohepatitis. Effects of treatment with lifestyle modification, PUFAs, or probiotics have not been validated with histologic analysis. Trials that are underway quantify steatosis magnetic resonance imaging-outcomes are anticipated.
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An integrated transcriptomic and epigenomic analysis identifies CD44 gene as a potential biomarker for weight loss within an energy-restricted program.
Samblas, M, Mansego, ML, Zulet, MA, Milagro, FI, Martinez, JA
European journal of nutrition. 2019;(5):1971-1980
Abstract
PURPOSE The interindividual variable response to weight-loss treatments requires the search for new predictive biomarkers for improving the success of weight-loss programs. The aim of this study is to identify novel genes that distinguish individual responses to a weight-loss dietary treatment by using the integrative analysis of mRNA expression and DNA methylation arrays. METHODS Subjects from Metabolic Syndrome Reduction in Navarra (RESMENA) project were classified as low (LR) or high (HR) responders depending on their weight loss. Transcriptomic (n = 24) and epigenomic (n = 47) patterns were determined by array-based genome-wide technologies in human white blood cells at the baseline of the treatment period. CD44 expression was validated by qRT-PCR and methylation degree of CpGs of the gene was validated by MassARRAY® EpiTYPER™ in a subsample of 47 subjects. CD44 protein levels were measured by ELISA in human plasma. RESULTS Different expression and DNA methylation profiles were identified in LR in comparison to HR. The integrative analysis of both array data identified four genes: CD44, ITPR1, MTSS1 and FBXW5 that were differently methylated and expressed between groups. CD44 showed higher expression and lower DNA methylation levels in LR than in HR. Although differences in CD44 protein levels between LR and HR were not statistically significant, a positive association was observed between CD44 mRNA expression and protein levels. CONCLUSIONS In summary, the combination of a genome-wide methylation and expression array dataset can be a useful strategy to identify novel genes that might be considered as predictors of the dietary response. CD44 gene transcription and methylation may be a possible candidate biomarker for weight-loss prediction.
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Chromium supplementation does not improve weight loss or metabolic and hormonal variables in patients with polycystic ovary syndrome: A systematic review.
Maleki, V, Izadi, A, Farsad-Naeimi, A, Alizadeh, M
Nutrition research (New York, N.Y.). 2018;:1-10
Abstract
Polycystic ovary syndrome (PCOS) is the most common endocrinopathy in women of reproductive age, and recently, chromium was discussed as an adjuvant way to manage it. Herein, a systematic review was conducted which centered on the effects of chromium on ovarian physiology with a focus on body mass index, as well as hormonal and metabolic dysfunctions in women suffering from PCOS. This review was performed using the guidelines from Preferred Reporting Items for Systematic Reviews. Clinical trials investigating chromium in women with PCOS with outcome measures related to metabolic and hormonal status were included. The search was conducted using PubMed, Scopus, and Google Scholar databases for clinical trials in the English language from the inception of the resources until May 2017 with the terms: chromium, chromium picolinate, CrP, polycystic ovary syndrome, PCOS, and sclerocystic ovary syndrome. The search resulted in 89 articles, and after inclusion and exclusion criteria were applied, 6 articles were selected for analysis. Two studies that evaluated the effect of chromium on body weight or body mass index reported no effect. Another study reported the beneficial effect of chromium on weight reduction. It seems that the effect of chromium in the reduction of blood glucose is insignificant, and results are inconsistent in relation to dyslipidemia. With regard to the effects of chromium on concentrations of sex hormones, a longer duration of treatment is needed to produce significant changes. The articles reviewed demonstrated that chromium supplementation has limited effects on weight reduction, glucose control, lipid profile, and hormonal disturbance of women with PCOS; however, more studies are needed due to the clinical changes observed in patients with PCOS after chromium supplementation.
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Effect of carbohydrate restriction-induced weight loss on aortic pulse wave velocity in overweight men and women.
Syed-Abdul, MM, Hu, Q, Jacome-Sosa, M, Padilla, J, Manrique-Acevedo, C, Heimowitz, C, Parks, EJ
Applied physiology, nutrition, and metabolism = Physiologie appliquee, nutrition et metabolisme. 2018;(12):1247-1256
Abstract
Increased aortic stiffness, measured by carotid-to-femoral pulse wave velocity (PWV), is an independent predictor of cardiovascular disease, and past data have shown that low-fat and low-energy diets, fed for 8-24 weeks, lower PWV. The purpose of this study was to determine whether a reduction in PWV would be achieved by dietary carbohydrate (CHO) restriction, shown to bring about weight loss over a shorter timeframe. Men (n = 10, age: 41.8 ± 10.2 years, BMI: 34.2 ± 3.0 kg/m2 (mean ± SD)) and women (n = 10, age: 38.6 ± 6.1 years, BMI: 33.5 ± 3.8 kg/m2) with characteristics of insulin resistance and the metabolic syndrome consumed a structured, CHO-restricted diet for 4 weeks (energy deficit, 645 kcal/day). For the whole group, subjects lost 5.4% ± 0.5% (P < 0.001) of body weight and experienced significant reductions in blood pressure (6%-8%), plasma insulin (34%), and triglycerides (34%). PWV was reduced by 6% ± 2% (7.1 ± 0.2 m/s to 6.7 ± 0.2 m/s, P = 0.008) and surprisingly, in women, it fell significantly (from 7.2 ± 0.3 m/s to 6.3 ± 0.3 m/s, P = 0.028), while no changes were observed in men (7.2 ± 0.3 vs. 7.0 ± 0.3 m/s, P = 0.144). This is the first study to demonstrate that weight loss can improve PWV in as little as 4 weeks and that dietary CHO restriction may be an effective treatment for reducing aortic stiffness in women. Future studies are needed to establish the mechanisms by which dietary CHO restriction may confer more cardiovascular benefits to women than to men.
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Improving Weight Loss by Combination of Two Temporary Antiobesity Treatments.
Genco, A, Ienca, R, Ernesti, I, Maselli, R, Casella, G, Bresciani, S, Mariani, S, Soricelli, E, Baglio, G, Lorenzo, M, et al
Obesity surgery. 2018;(12):3733-3737
Abstract
BACKGROUND It is generally accepted that the efficacy with an intragastric balloon decreases after the first 4 months of treatment. Aim of this study is to evaluate if the association of a very low-calorie ketogenic diet (VLCKD) can improve the results in terms of weight loss parameters and co-morbidities, as compared to usually prescribed low-calorie diet (LCD). METHODS For the present study (January 2016-June 2017), 80 patients (20 M/60 F, mean age 37.8 ± 6.1 years; excess weight 56 ± 10 kg; mean BMI 37.2 ± 3.8 kg/m2) underwent Orbera positioning. After 4 months, they were randomized into two groups according to the type of treatment: group A (Bioenterics intragastric balloon - Orbera + VLCKD) (n = 40), and group B (Orbera + LCD) (n = 40). RESULTS All patients completed the study with good adherence to diet therapy treatment allocation. After the 6-month treatment period, at time of Orbera removal, mean weight loss was 19 kg and 12 kg in groups A and B respectively (p < 0.05). Mean BMI was 28.9 ± 2.8 and 31.6 ± 3.1 kg/m2 (p < 0.05), and %EWL was 33.1 ± 3.3 and 21.1 ± 2.9 (p < 0.05) in groups A and B respectively. During the last 2 months in group A, the mean weight loss was 8 kg, while in Group B, the main weight loss was 3 kg (p < 0.001). The VLCKD treatment induced a more significant reduction of major comorbidities related to metabolic syndrome. CONCLUSIONS This study clearly indicates the efficacy of the prescription of very low-calorie ketogenic diet improving the efficacy of intragastric balloon positioning.
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Link between chemerin, central obesity, and parameters of the Metabolic Syndrome: findings from a longitudinal study in obese children participating in a lifestyle intervention.
Niklowitz, P, Rothermel, J, Lass, N, Barth, A, Reinehr, T
International journal of obesity (2005). 2018;(10):1743-1752
Abstract
OBJECTIVE Chemerin has been suggested as a potential link between obesity and associated comorbidities in humans. Therefore, we studied the relationships between chemerin, parameters of fat mass, and Metabolic Syndrome (MetS) in obese children before and after weight reduction. METHODS We determined chemerin, bioactive leptin (bioLep), BMI-SDS, waist circumference (WC), body fat based on skinfold measurements and bioimpedance analyses, lipids, transaminases, insulin resistance index HOMA, and blood pressure in 88 obese children participating in a lifestyle intervention at baseline and 1 year later. Furthermore, we determined chemerin concentrations in 23 normal-weight children. RESULTS Obese children demonstrated significantly (p < 0.001) higher chemerin concentrations compared to normal-weight children (96.2 ± 23.0 versus 63.1 ± 12.4 ng/ml). The chemerin concentrations were not related to age or gender. Prepubertal children had higher (p = 0.024) chemerin concentrations than pubertal children (71.0 ± 13.4 versus 58.0 ± 8.9 ng/ml). Weight loss was associated with a decrease of chemerin (-14.0 ± 22.0 ng/ml; p < 0.001) and an improvement of all parameters of the MetS. Chemerin was significantly related to BMI-SDS, WC, and bioLep in cross-sectional and longitudinal analyses. Chemerin and its changes were significantly related to insulin, HDL-cholesterol, triglycerides and their changes in multiple linear regression analyses adjusted to age, gender, pubertal stage, leptin and BMI. CONCLUSIONS Since chemerin was related to parameters of central fat mass and MetS both in cross-sectional and longitudinal analyses these findings suggest an impact of chemerin on factors of the MetS in obese children.
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Lifestyle intervention for morbid obesity: effects on liver steatosis, inflammation, and fibrosis.
Hohenester, S, Christiansen, S, Nagel, J, Wimmer, R, Artmann, R, Denk, G, Bischoff, M, Bischoff, G, Rust, C
American journal of physiology. Gastrointestinal and liver physiology. 2018;(3):G329-G338
Abstract
The prevalence of obesity-related nonalcoholic fatty liver disease (NAFLD) is rising. NAFLD may result in nonalcoholic steatohepatitis (NASH), progressing to liver cirrhosis. Weight loss is recommended to treat obesity-related NASH. Lifestyle intervention may improve NASH; however, pertinent trials have so far focused on overweight patients, whereas patients with obesity are at highest risk of developing NAFLD. Furthermore, reports of effects on liver fibrosis are scarce. We evaluated the effect of lifestyle intervention on NAFLD in a real-life cohort of morbidly obese patients. In our observational study, 152 patients underwent lifestyle intervention, with a follow-up of 52 weeks. Noninvasive measures of obesity, metabolic syndrome, liver steatosis, liver damage, and liver fibrosis were analyzed. Treatment response in terms of weight loss was achieved in 85.1% of patients. Dysglycemia and dyslipidemia improved. The proportion of patients with fatty liver dropped from 98.1 to 54.3% ( P < 0.001). Weight loss >10% was associated with better treatment response ( P = 0.0009). Prevalence of abnormal serum transaminases fell from 81.0 to 50.5% ( P < 0.001). The proportion fibrotic patients, as determined by the NAFLD fibrosis score, dropped from 11.8 to 0% ( P < 0.05). Low serum levels of adiponectin correlated with degree of liver damage, i.e., serum liver transaminases ( r = -0,32, P < 0.05). Serum levels of adiponectin improved with intervention. In conclusion, lifestyle intervention effectively targeted obesity and the metabolic syndrome. Liver steatosis, damage and fibrosis were ameliorated in this real-life cohort of morbidly obese patients, mediated in part by changes in the adipokine profile. Patients with weight loss of >10% seemed to benefit most. NEW & NOTEWORTHY We demonstrate new evidence that lifestyle intervention is effective in treating NAFLD in the important group of patients with (morbid) obesity. Although current guidelines on the therapy of NASH recommend weight loss of 5-7%, weight reduction >10% may be favorable in morbid obesity. Serum levels of adipokines correlate with liver damage, which is indicative of their pathogenetic importance in human NASH. Our study adds to the limited body of evidence that NAFLD-associated liver fibrosis may resolve with lifestyle intervention.