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Liver fat scores do not reflect interventional changes in liver fat content induced by high-protein diets.
Kabisch, S, Markova, M, Hornemann, S, Sucher, S, Pivovarova-Ramich, O, Machann, J, Hierholzer, J, Rohn, S, Pfeiffer, AFH
Scientific reports. 2021;(1):8843
Abstract
Non-alcoholic fatty liver disease (NAFLD) is common in Metabolic Syndrome and type 2 diabetes (T2DM), driven by energy imbalance, saturated fats and simple carbohydrates. NAFLD requires screening and monitoring for late complications. Liver fat indices may predict NAFLD avoiding expensive or invasive gold-standard methods, but they are poorly validated for use in interventional settings. Recent data indicate a particular insensitivity to weight-independent liver fat reduction. We evaluated 31 T2DM patients, completing a randomized intervention study on isocaloric high-protein diets. We assessed anthropometric measures, intrahepatic lipid (IHL) content and serum liver enzymes, allowing AUROC calculations as well as cross-sectional and longitudinal Spearman correlations between the fatty liver index, the NAFLD-liver fat score, the Hepatosteatosis Index, and IHL. At baseline, all indices predicted NAFLD with moderate accuracy (AUROC 0.731-0.770), supported by correlation analyses. Diet-induced IHL changes weakly correlated with changes of waist circumference, but no other index component or the indices themselves. Liver fat indices may help to easily detect NAFLD, allowing cost-effective allocation of further diagnostics to patients at high risk. IHL reduction by weight-independent diets is not reflected by a proportional change in liver fat scores. Further research on the development of treatment-sensitive indices is required.Trial registration: The trial was registered at clinicaltrials.gov: NCT02402985.
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The Use of a Stem and Leaf Aqueous Extract of Cissus quadrangularis (CQR-300) to Reduce Body Fat and Other Components of Metabolic Syndrome in Overweight Participants.
Nash, R, Azantsa, B, Kuate, D, Singh, H, Oben, J
Journal of alternative and complementary medicine (New York, N.Y.). 2019;(1):98-106
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BACKGROUND Previous work had shown the ability of an aqueous leaf and stem extract of Cissus quandrangularis (300 mg of CQR, CQR-300) to improve components of metabolic syndrome (MS) in overweight individuals. OBJECTIVE This small pilot study aimed to confirm the efficacy of CQR-300 in reducing the percentage body fat measured using two different methods-bioelectrical impedance assay versus dual-energy X-ray absorptiometry (DEXA). DESIGN The study was an 8-week double-blind, placebo-controlled pilot trial on 67 individuals who were requested by a dietary counselor to maintain their normal exercise and dietary routines. Participants were randomly divided into two groups, placebo (32 participants) and the CQR-300 group (35 participants), and received 300 mg of corn starch or CQR-300 daily. METHODS Body fat was measured by bioelectrical impedance using a TANITA impedance meter and by DEXA, with blood samples taken at baseline and at 8 weeks for the measurement of lipid parameters. RESULTS After 8 weeks of treatment, participants of the placebo group showed a 1.05% decrease in body fat as determined by bioelectrical impedance analysis, but no difference using DEXA. In the same time period, the CQR-300 group had an 8.9% and 12.8% decreases in the body fat as measured by impedance and DEXA, respectively. These values were significantly (p < 0.05) lower than the placebo. Compared with the placebo, the CQR-300 group demonstrated significant (p < 0.05) decreases in the waist and hip circumferences, systolic and diastolic blood pressures, total cholesterol, triglycerides, fasting blood glucose, as well as leptin levels. On the contrary, there were significant (p < 0.05) increases in HDL-cholesterol and adiponectin levels. CONCLUSION CQR-300 administered as a single 300 mg dose daily was effective in reducing body fat as well as improving blood parameters associated with MS.
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Vitamin D Daily versus Monthly Administration: Bone Turnover and Adipose Tissue Influences.
Dalle Carbonare, L, Valenti, MT, Del Forno, F, Piacentini, G, Pietrobelli, A
Nutrients. 2018;(12)
Abstract
Vitamin D is involved in bone metabolism and in many various extra-skeletal diseases such as malabsorption syndromes, cardiovascular and metabolic diseases, cancer, and autoimmune and neurological diseases. However, data on the optimal route of administration are not consistent. The aims of our study were to analyze not only the influence of daily vs. monthly administration of vitamin D on bone metabolism and bone turnover, but also the effects of different routes of administration on fat mass in a cohort of adults with low levels of 25(OH) vitamin D3 at baseline. We analyzed 44 patients with hypovitaminosis at baseline and after six months of two different regimens of administration: seven drops (1750 IU)/day vs. 50,000 IU/month. We found that the two regimens were equivalent; 36 out of 44 patients reached the normal range of vitamin D after six months of treatment. Interestingly, the main determinant of vitamin D at baseline was the waist circumference. In addition, 22 patients treated by monthly regimen were evaluated after 18 months of treatment. At the end of follow-up, patients showed normal levels of vitamin D, with increased calcium levels and decreased bone turnover. Waist circumference also decreased. Our results support the efficacy of vitamin D3 given monthly both for correcting hypovitaminosis and for maintaining vitamin D levels. The relationship between serum 25(OH)vitamin D3 concentration and waist circumference supports vitamin D having a protective role in the current setting, since waist size is directly associated with the risk of cardiovascular and metabolic diseases.
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Effect of Pericardial Fat Volume and Density on Markers of Insulin Resistance and Inflammation in Patients With Human Immunodeficiency Virus Infection.
Longenecker, CT, Margevicius, S, Liu, Y, Schluchter, MD, Yun, CH, Bezerra, HG, McComsey, GA
The American journal of cardiology. 2017;(8):1427-1433
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Treated human immunodeficiency virus (HIV) infection is characterized by ectopic fat deposition, a persistent inflammatory state, and increased cardiometabolic risk. In this secondary analysis of a placebo controlled trial of rosuvastatin among 147 HIV+ subjects (median age 46; 78% men) on stable antiretroviral therapy, we aimed to evaluate longitudinal associations between computed tomography (CT) measures of pericardial fat (PCF) volume and density, insulin resistance, and inflammation. We measured PCF volume and density (mean attenuation in Hounsfield units) by noncontrast gated CT at baseline and week 96. Homeostatic model of insulin resistance was calculated from fasting insulin and glucose at entry, 24, 48, and 96 weeks. At baseline, insulin resistance correlated positively with PCF volume and negatively with density. Similarly divergent correlations of volume and density were observed with waist:hip ratio, nadir CD4+ count, and duration of antiretroviral therapy. In a linear mixed model, PCF density was associated with insulin resistance independent of PCF volume, body mass index, metabolic syndrome, and biomarkers of immune activation and systemic inflammation; however, baseline PCF measures were not associated with longitudinal changes in insulin resistance. Soluble CD163, a marker of monocyte activation, positively correlated with PCF volume and was associated with insulin resistance in linear models. Statin treatment assignment did not affect PCF volume or density change (both p > 0.8). In conclusion, the quantity and quality (i.e., radiodensity) of PCF are differentially related to insulin resistance and inflammation in patients with treated HIV infection.
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Effects of a community-based weight loss intervention on adipose tissue circulating factors.
Miller, GD, Isom, S, Morgan, TM, Vitolins, MZ, Blackwell, C, Brosnihan, KB, Diz, DI, Katula, J, Goff, D
Diabetes & metabolic syndrome. 2014;(4):205-11
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AIMS: Obesity is associated with metabolic dysfunctions, which may be mediated by changes in adipose tissue signaling factors. These molecules are denoted as Adipose Tissue Generated Mediators of CardioVascular Risk (ATGMCVR) here, and include leptin, adiponectin, C-reactive protein (CRP), interleukin 6 (IL-6), tumor necrosis factor alpha (TNFα), and plasminogen activator inhibitor 1 (PAI-1). This study examined the effect of a weight loss program on ATGMCVR in obese adults with prediabetes. MATERIALS AND METHODS Subjects were randomized to usual care (UC; n=15) or lifestyle weight loss groups (LWL; n=15). LWL was a community-based weight loss intervention to promote physical activity and healthy eating. ATGMCVR at 1-year were compared between groups by analysis of covariance; baseline value of the mediator was the covariate. Baseline means for ATGMCVR were compared between those with (n=21) and without (n=9) metabolic syndrome (MetS). RESULTS At baseline, subjects were 58±9 (SD) years, 70% female, with a BMI of 34±4kg/m(2). One-year weight loss (%) was 7.8±6.0% for LWL and 1.7±4.5% for UC. Group differences at 1-year were noted (adjusted means [95%CI] for UC and LWL, respectively) for adiponectin (8526.3 [7397.7, 9827]; 10,870.9 [9432.0, 12,529.3]ng/ml; p=0.02), leptin (30.4 [26.1, 35.4]; 23.7 [20.3, 27.5]ng/ml; p=0.02), IL-6 (0.4 [0.3, 0.5]; 0.2 [0.1, 0.2] pg/ml; p=0.001), and PAI-1 (50 [42.7, 58.7]; 36.2 [30.8, 42.4]pg/ml; p=0.01). No differences in baseline ATGMCVR were seen between subjects with and without MetS. CONCLUSION These findings suggest ATGMCVR can be improved with weight loss; larger studies are needed to determine if improvements in metabolic dysfunction are related to changes in ATGMCVR.
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Reducing effect of calcium in combination with magnesium and lactulose on body fat mass in middle-aged Japanese women.
Seki, N, Asano, Y, Ochi, H, Abe, F, Uenishi, K, Kudou, H
Asia Pacific journal of clinical nutrition. 2013;(4):557-64
Abstract
BACKGROUND It has been reported that adequate calcium intake decreases body fat and appropriate intakes of magnesium suppress the development of the metabolic syndrome. Furthermore, lactulose increases the absorption of calcium and magnesium. An optimal combination of calcium, magnesium and lactulose may therefore reduce body fat mass. METHODS An open-label randomized controlled trial was conducted to investigate the body fat-reducing effects of a test food containing 300 mg calcium, 150 mg magnesium, and 4.0 g lactulose. Body composition parameters and blood hormone and urine mineral concentrations were measured at baseline and at 6 and 12 months thereafter. Whole-body fat mass was measured with dual-energy x-ray absorptiometry. RESULTS Seventy-six middle-aged Japanese women (47.5±4.7 years) were randomized to the intake group (n=48) or the non-intake control group (n=28). At 12 months the difference in body fat mass change between the two groups (intake group - control group) was -0.8 kg (95% CI: -1.5 - 0.0 kg, p=0.046), although there were no differences in anthropometric data between the two groups. Body fat percentage at 12 months tended to be lower in the intake group, but the difference was not significant (p=0.09). CONCLUSIONS These findings may suggest that calcium in combination with magnesium and lactulose can reduce body fat mass in middle-aged Japanese women. However, the contribution of magnesium and lactulose are unclear in this study. Further studies are needed to clarify these contributions.
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Transcriptomic coordination in the human metabolic network reveals links between n-3 fat intake, adipose tissue gene expression and metabolic health.
Morine, MJ, Tierney, AC, van Ommen, B, Daniel, H, Toomey, S, Gjelstad, IM, Gormley, IC, Pérez-Martinez, P, Drevon, CA, López-Miranda, J, et al
PLoS computational biology. 2011;(11):e1002223
Abstract
Understanding the molecular link between diet and health is a key goal in nutritional systems biology. As an alternative to pathway analysis, we have developed a joint multivariate and network-based approach to analysis of a dataset of habitual dietary records, adipose tissue transcriptomics and comprehensive plasma marker profiles from human volunteers with the Metabolic Syndrome. With this approach we identified prominent co-expressed sub-networks in the global metabolic network, which showed correlated expression with habitual n-3 PUFA intake and urinary levels of the oxidative stress marker 8-iso-PGF(2α). These sub-networks illustrated inherent cross-talk between distinct metabolic pathways, such as between triglyceride metabolism and production of lipid signalling molecules. In a parallel promoter analysis, we identified several adipogenic transcription factors as potential transcriptional regulators associated with habitual n-3 PUFA intake. Our results illustrate advantages of network-based analysis, and generate novel hypotheses on the transcriptomic link between habitual n-3 PUFA intake, adipose tissue function and oxidative stress.
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Greater weight loss and hormonal changes after 6 months diet with carbohydrates eaten mostly at dinner.
Sofer, S, Eliraz, A, Kaplan, S, Voet, H, Fink, G, Kima, T, Madar, Z
Obesity (Silver Spring, Md.). 2011;(10):2006-14
Abstract
This study was designed to investigate the effect of a low-calorie diet with carbohydrates eaten mostly at dinner on anthropometric, hunger/satiety, biochemical, and inflammatory parameters. Hormonal secretions were also evaluated. Seventy-eight police officers (BMI >30) were randomly assigned to experimental (carbohydrates eaten mostly at dinner) or control weight loss diets for 6 months. On day 0, 7, 90, and 180 blood samples and hunger scores were collected every 4 h from 0800 to 2000 hours. Anthropometric measurements were collected throughout the study. Greater weight loss, abdominal circumference, and body fat mass reductions were observed in the experimental diet in comparison to controls. Hunger scores were lower and greater improvements in fasting glucose, average daily insulin concentrations, and homeostasis model assessment for insulin resistance (HOMA(IR)), T-cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, C-reactive protein (CRP), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) levels were observed in comparison to controls. The experimental diet modified daily leptin and adiponectin concentrations compared to those observed at baseline and to a control diet. A simple dietary manipulation of carbohydrate distribution appears to have additional benefits when compared to a conventional weight loss diet in individuals suffering from obesity. It might also be beneficial for individuals suffering from insulin resistance and the metabolic syndrome. Further research is required to confirm and clarify the mechanisms by which this relatively simple diet approach enhances satiety, leads to better anthropometric outcomes, and achieves improved metabolic response, compared to a more conventional dietary approach.
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Metabolic syndrome and changes in body fat from a low-fat diet and/or exercise randomized controlled trial.
Camhi, SM, Stefanick, ML, Katzmarzyk, PT, Young, DR
Obesity (Silver Spring, Md.). 2010;(3):548-54
Abstract
It is difficult to identify the successful component(s) related to changes in metabolic syndrome (MetS) from lifestyle interventions: the weight loss, the behavior change, or the combination. The purpose of this study is to determine the effects of a weight-stable randomized controlled trial of low-fat diet and exercise, alone and in combination, on MetS. Men (n = 179) and postmenopausal women (n = 149) with elevated low-density lipoprotein cholesterol (LDL-C) and low high-density lipoprotein cholesterol (HDL-C) were randomized into a 1-year, weight-stable trial with four treatment groups: control (C), diet (D), exercise (E), or diet plus exercise (D+E). MetS was defined using a continuous score. Changes in MetS score (DeltaMetS) were compared between groups using analysis of covariance, stratified by gender and using two models, with and without baseline and change in percent body fat (DeltaBF) as a covariate. In men, DeltaMetS was higher for D vs. C (P = 0.04), D+E vs. C (P = 0.0002), and D+E vs. E (P = 0.02). For women, DeltaMetS was greater for D vs. C (P = 0.045), E vs. C (P = 0.02), and D+E vs. C (P = 0.004). After adjusting for DeltaBF, all differences between groups were attenuated and no longer significant. DeltaMetS were associated with DeltaBF for both men (P < 0.0001) and women (P = 0.004). After adjustment for DeltaBF, low-fat diet alone and in combination with exercise had no effect on MetS. The key component for MetS from low-fat diet and/or increased physical activity appears to be body fat loss.
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Rosiglitazone improves lipoatrophy in patients receiving thymidine-sparing regimens.
Tungsiripat, M, Bejjani, DE, Rizk, N, O'riordan, MA, Ross, AC, Hileman, C, Storer, N, Harrill, D, McComsey, GA
AIDS (London, England). 2010;(9):1291-8
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OBJECTIVE Thymidine reverse transcriptase inhibitors (tNRTI) are strong inhibitors of PPAR-gamma and clearly implicated as a cause of lipoatrophy. Thiazolidenediaones (TZD), potent PPAR-gamma agonists, would be expected to be beneficial in HIV lipoatrophy, but prior studies have been conflicting. None specifically excluded the use of tNRTIs. We report the first study in individuals treated with tNRTI-sparing regimens using a TZD for treatment of HIV lipoatrophy. DESIGN This double-blind, placebo-controlled study evaluated limb fat in HIV-infected individuals with lipoatrophy who discontinued tNRTI at least 24 weeks prior to enrollment. METHODS Individuals were randomized to rosiglitazone vs. placebo for 48 weeks. Dual energy X-ray absorptiometry (DEXA)-scans and fasting metabolic assessments were serially performed. RESULTS We enrolled 71 individuals, 17% were female and 51% white. Baseline characteristics were similar between groups except for higher total cholesterol in the placebo group (P = 0.04). At 48 weeks, limb fat (grams) increased significantly (P = 0.02) more in the rosiglitazone than in the placebo group: median (IQR) 448 (138, 1670) vs. 153 (-100, 682), respectively. Of lipids parameters, only total cholesterol increased significantly more in the rosiglitazone group (P = 0.008). Prevalence of metabolic syndrome and total bone mineral density did not change between or within groups. CONCLUSION In the absence of tNRTI, rosiglitazone significantly improves lipoatrophy without deleterious effect on bone mineral density. Total cholesterol, but not triglycerides, significantly increased in the rosiglitazone arm. The glitazones may be a promising addition for accelerating fat recovery in individuals who had switched off tNRTI and remain with significant lipoatrophy.