scholarly journals Exercise plasma metabolomics and xenometabolomics in obese, sedentary, insulin-resistant women: impact of a fitness and weight loss intervention

2019 ◽  
Vol 317 (6) ◽  
pp. E999-E1014 ◽  
Author(s):  
Dmitry Grapov ◽  
Oliver Fiehn ◽  
Caitlin Campbell ◽  
Carol J. Chandler ◽  
Dustin J. Burnett ◽  
...  

Insulin resistance has wide-ranging effects on metabolism, but there are knowledge gaps regarding the tissue origins of systemic metabolite patterns and how patterns are altered by fitness and metabolic health. To address these questions, plasma metabolite patterns were determined every 5 min during exercise (30 min, ∼45% of V̇o2peak, ∼63 W) and recovery in overnight-fasted sedentary, obese, insulin-resistant women under controlled conditions of diet and physical activity. We hypothesized that improved fitness and insulin sensitivity following a ∼14-wk training and weight loss intervention would lead to fixed workload plasma metabolomics signatures reflective of metabolic health and muscle metabolism. Pattern analysis over the first 15 min of exercise, regardless of pre- versus postintervention status, highlighted anticipated increases in fatty acid tissue uptake and oxidation (e.g., reduced long-chain fatty acids), diminution of nonoxidative fates of glucose [e.g., lowered sorbitol-pathway metabolites and glycerol-3-galactoside (possible glycerolipid synthesis metabolite)], and enhanced tissue amino acid use (e.g., drops in amino acids; modest increase in urea). A novel observation was that exercise significantly increased several xenometabolites (“non-self” molecules, from microbes or foods), including benzoic acid-salicylic acid-salicylaldehyde, hexadecanol-octadecanol-dodecanol, and chlorogenic acid. In addition, many nonannotated metabolites changed with exercise. Although exercise itself strongly impacted the global metabolome, there were surprisingly few intervention-associated differences despite marked improvements in insulin sensitivity, fitness, and adiposity. These results and previously reported plasma acylcarnitine profiles support the principle that most metabolic changes during submaximal aerobic exercise are closely tethered to absolute ATP turnover rate (workload), regardless of fitness or metabolic health status.

2009 ◽  
Vol 161 (1) ◽  
pp. 51-56 ◽  
Author(s):  
Barbara Antuna-Puente ◽  
Emmanuel Disse ◽  
May Faraj ◽  
Marie-Eve Lavoie ◽  
Martine Laville ◽  
...  

ObjectiveTo evaluate the validity of a new lipid-based index (Disse index) in assessing insulin sensitivity (IS) compared with the hyperinsulinemic-euglycemic (HIEG) clamp in overweight and obese, non-diabetic, postmenopausal women, before and after a weight loss intervention.Research design and methodsAssociation between Disse index and the HIEG clamp was evaluated in 86 non-diabetic postmenopausal overweight and obese women before and after weight loss. Percentage changes (%Δ) were calculated for several fasting indices and compared with %Δ of HIEG clamp.ResultsWe observed a strong correlation between Disse index and HIEG clamp (r=0.69, P<0.001). This association was higher than those of homeostasis model assessment (HOMA), quantitative insulin sensitivity check index (QUICKI), and McAuley indices while no significant difference was observed with Revised-QUICKI. Percent change of Disse index (pre- versus post-weight loss program) was significantly correlated with %Δ of HIEG clamp (r=0.34, P<0.01). This correlation was similar to those observed for the other indices tested.ConclusionsWe validated the reliability of Disse index in assessing IS in non-diabetic post-menopausal overweight and obese women, before and after weight loss intervention. Disse index may be useful not only for insulin resistant diagnostics in this type of population, but also for the IS follow-up after a weight-loss program and weight stabilization. The presence of lipid elements in this fasting index improves the estimation of IS in overweight and obese non-diabetic post-menopausal women and could add more information about peripheral IS.


2007 ◽  
Vol 112 (11) ◽  
pp. 557-565 ◽  
Author(s):  
Jan Polak ◽  
Zuzana Kovacova ◽  
Martin Jacek ◽  
Eva Klimcakova ◽  
Michaela Kovacikova ◽  
...  

Adiponectin is involved in the regulation of glucose and fatty acid metabolism, influences whole-body insulin sensitivity and protects arterial walls against the development of atherosclerosis. Plasma adiponectin is decreased in obese, insulin-resistant and Type 2 diabetic patients. Adiponectin circulates in plasma as high-, medium- and low-molecular-weight (‘mass’) forms (HMW, MMW and LMW respectively). The HMW form is believed to be closely associated with insulin sensitivity. The aim of the present study was to investigate whether diet-induced changes in body weight and insulin sensitivity were associated with changes in the quantity of adiponectin multimeric complexes. A total of 20 overweight or obese women (age, 39.4±9.5 years; body mass index, 32.2±6.4 kg/m2) underwent 12 weeks of low caloric diet (600 kcal/day less than energy requirements; where 1 kcal≈4.184 kJ). Plasma samples were drawn before and after the study for biochemical analysis and Western blot detection of adiponectin multimeric complexes. The hypocaloric diet resulted in a weight reduction (89.8±16.4 kg compared with 83.1±15.6 kg; P<0.001) and an improvement in whole-body insulin sensitivity, as measured by HOMA (homoeostasis model assessment index; 1.9±0.8 compared with 1.5±0.7; P=0.013). Increases in the quantities of the HMW, MMW and LMW forms by 5.5, 8.5 and 18.1% respectively, were observed (P<0.05 for all of the forms). Total plasma adiponectin was increased by 36% with borderline significance (P=0.08). No correlations between changes in adiponectin complexes and changes in indices of insulin sensitivity were observed. In conclusion, diet-induced weight loss improved insulin sensitivity as well as increased the amount of HMW, MMW and LMW adiponectin complexes in plasma.


2020 ◽  
Vol 30 (Supplement_5) ◽  
Author(s):  
A Penesova ◽  
J Babjakova ◽  
A Havranova ◽  
R Imrich ◽  
M Vlcek

Abstract Background Central obesity and dyslipidemia are a cardinal features of the metabolic syndrome and represents increased cardiometabolic risk. It has been shown that weight loss is capable to improve insulin sensitivity and lipid parameters. The aim of our study was to analyze the effect of a weight-lowering program (diet and physical activity) on LDL- and HDL-cholesterol subfractions and cardiometabolic risk factors (waist circumference, blood pressure, insulin sensitivity, physical fitness). Methods We studied 2 groups of obese subjects, group A composed of 43 patients with obesity grade 1 and 2 (30F/13M; age: 43.2 ±12.4 years; BMI 31.3 ± 6.1 kg/m2); group B composed of patients with obesity grade 3 (6F/7M; age: 34.7 ±9.8 years; BMI 51.7 ± 7.9 kg/m2). The weight loss interventional program (NCT02325804) in duration of 8-week (group A) or 24 weeks (group B) consisted of hypocaloric diet and physical activity. Body composition, physical fitness, blood lipids profile (using the Lipoprint system (Quantimetrix Corp., CA, USA), and insulin sensitivity were measured. Results The average weight loss was 7.3±1.9 kg in group A and 35.3±16.0 kg in group B. Systolic, diastolic blood pressure (BP) as well as heart rate decreased in group A, in group B only systolic BP. Fasting plasma glucose and insulin decreased as well as insulin sensitivity and physical fitness has been improved after intervention. Total, LDL2, HDL2 cholesterol, as well as triglycerides (TG) decreased with weight in group A and total, LDL, TG, VLDL, LDL2 large, and small HDL subfractions decreased and intermediate HDL increased in group B. Conclusions Short term life style intervention (diet and physical activity) in patients with obesity lead to notable improvement of cardiometabolic parameters (decreased body fat mass, improved insulin sensitivity, lipid profile) as well as atheroprotective changes in LDL subfractions. Funding Supported by grants APVV 17-0099; VEGA 2/0129/20; VEGA 2/0072/18 Key messages Short term life style intervention in patients with obesity lead to notable improvement of cardiometabolic parameters. Weight-lowering program (diet and physical activity) lead to positive changes in LDL- and HDL-cholesterol subfractions.


2011 ◽  
Vol 10 (1) ◽  
pp. 66 ◽  
Author(s):  
Ricardo K Yamazaki ◽  
Gleisson AP Brito ◽  
Isabela Coelho ◽  
Danielle CT Pequitto ◽  
Adriana A Yamaguchi ◽  
...  

2012 ◽  
Vol 26 (S1) ◽  
Author(s):  
Caitlin Campbell ◽  
Carol J. Chandler ◽  
Dustin J. Burnett ◽  
Elaine C. Souza ◽  
Gretchen A. Casazza ◽  
...  

2021 ◽  
Author(s):  
Santosh Kumari ◽  
Matthew Bubak ◽  
Hayden M. Schoenberg ◽  
Arik Davidyan ◽  
Christian J. Elliehausen ◽  
...  

The antidiabetic medication metformin has been proposed to be the first drug tested to target aging and extend healthspan in humans. While there is extensive epidemiological support for the health benefits of metformin in patient populations, it is not clear if these protective effects apply to those free of age-related disease. Our previous data in older adults without diabetes suggest a dichotomous change in insulin sensitivity and skeletal muscle mitochondrial adaptations after metformin treatment when co-prescribed with exercise. Those who entered the study as insulin sensitive had no change to detrimental effects while those who were insulin resistant had positive changes. The objective of this clinical trial is to determine if 1) antecedent metabolic health and 2) skeletal muscle mitochondrial remodeling and function mediate the positive or detrimental effects of metformin monotherapy, independent of exercise, on the metabolism and biology of aging. In a randomized, double blind clinical trial, adults free of chronic disease (n=148, 40-75 years old) are stratified as either insulin sensitive or insulin resistant based on HOMA-IR (≤2.2 or ≥2.5) and take 1500 mg/day of metformin or placebo for 12 weeks. Hyperinsulinemic-euglycemic clamps and skeletal muscle biopsies are performed before and after 12 weeks to assess primary outcomes of peripheral insulin sensitivity and mitochondrial remodeling and function. Findings from this trial will identify clinical characteristics and cellular mechanisms involved in modulating the effectiveness of metformin treatment to target aging that could inform larger phase 3 clinical trials aimed at testing aging as an indication for metformin.


2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Sofiya Gancheva ◽  
Meriem Ouni ◽  
Tomas Jelenik ◽  
Chrysi Koliaki ◽  
Julia Szendroedi ◽  
...  

Abstract The mechanisms underlying improved insulin sensitivity after surgically-induced weight loss are still unclear. We monitored skeletal muscle metabolism in obese individuals before and over 52 weeks after metabolic surgery. Initial weight loss occurs in parallel with a decrease in muscle oxidative capacity and respiratory control ratio. Persistent elevation of intramyocellular lipid intermediates, likely resulting from unrestrained adipose tissue lipolysis, accompanies the lack of rapid changes in insulin sensitivity. Simultaneously, alterations in skeletal muscle expression of genes involved in calcium/lipid metabolism and mitochondrial function associate with subsequent distinct DNA methylation patterns at 52 weeks after surgery. Thus, initial unfavorable metabolic changes including insulin resistance of adipose tissue and skeletal muscle precede epigenetic modifications of genes involved in muscle energy metabolism and the long-term improvement of insulin sensitivity.


2009 ◽  
Vol 103 (8) ◽  
pp. 1230-1235 ◽  
Author(s):  
Virginie Messier ◽  
Jessy Hayek ◽  
Antony D. Karelis ◽  
Lyne Messier ◽  
Éric Doucet ◽  
...  

The objective of the present study was to examine anthropometric, metabolic, psychosocial and dietary factors associated with dropout in a 6-month weight loss intervention aimed at reducing body weight by 10 %. The study sample included 137 sedentary, overweight and obese postmenopausal women, participating in a weight loss intervention that consisted of either energy restriction (ER) or ER with resistance training (ER+RT). Anthropometric (BMI, percent lean body mass, percent fat mass, visceral adipose tissue and waist circumference), metabolic (total energy expenditure, RMR, insulin sensitivity and fasting plasma levels of leptin and ghrelin), psychosocial (body esteem, self-esteem, stress, dietary restraint, disinhibition, hunger, quality of life, self-efficacy, perceived benefits for controlling weight and perceived risk) and dietary (3-d food record) variables were measured. Thirty subjects out of 137 dropped out of the weight loss programme (22 %), with no significant differences in dropout rates between those in the ER and the ER+RT groups. Overall, amount of weight loss was significantly lower in dropouts than in completers ( − 1·7 (sd 3·5) v. − 5·6 (sd 4·3) kg, P < 0·05); weekly weight loss during the first 4 weeks was also significantly lower. Dropouts consumed fewer fruit servings than completers (1·7 (sd 1·1) v. 2·7 (sd 1·53), P < 0·05) and had higher insulin sensitivity levels (12·6 (sd 3·8) v. 11·1 (sd 2·8) mg glucose/min per kg fat-free mass, P < 0·05). The present results suggest that the rate of weight loss during the first weeks of an intervention plays an important role in the completion of the programme. Thus, participants with low rates of initial weight loss should be monitored intensely to undertake corrective measures to increase the likelihood of completion.


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