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Effects of weight loss and exercise on insulin resistance, and intramyocellular triacylglycerol, diacylglycerol and ceramide.

ABSTRACT: Intramyocellular lipids, including diacylglycerol (DAG) and ceramides, have been linked to insulin resistance. This randomised repeated-measures study examined the effects of diet-induced weight loss (DIWL) and aerobic exercise (EX) on insulin sensitivity and intramyocellular triacylglycerol (IMTG), DAG and ceramide.Sixteen overweight to obese adults (BMI 30.6?±?0.8; 67.2?±?4.0 years of age) with either impaired fasting glucose, or impaired glucose tolerance completed one of two lifestyle interventions: DIWL (n?=?8) or EX (n?=?8). Insulin sensitivity was determined using hyperinsulinaemic-euglycaemic clamps. Intramyocellular lipids were measured in muscle biopsies using histochemistry and tandem mass spectrometry.Insulin sensitivity was improved with DIWL (20.6?±?4.7%) and EX (19.2?±?12.9%). Body weight and body fat were decreased by both interventions, with greater decreases in DIWL compared with EX. Muscle glycogen, IMTG content and oxidative capacity were all significantly (p?

SUBMITTER: Dube JJ

PROVIDER: S-EPMC3804898 | biostudies-literature | 2011 May

REPOSITORIES: biostudies-literature

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Effects of weight loss and exercise on insulin resistance, and intramyocellular triacylglycerol, diacylglycerol and ceramide.

Dubé J J JJ Amati F F Toledo F G S FG Stefanovic-Racic M M Rossi A A Coen P P Goodpaster B H BH

Diabetologia 20110217 5

<h4>Aims/hypothesis</h4>Intramyocellular lipids, including diacylglycerol (DAG) and ceramides, have been linked to insulin resistance. This randomised repeated-measures study examined the effects of diet-induced weight loss (DIWL) and aerobic exercise (EX) on insulin sensitivity and intramyocellular triacylglycerol (IMTG), DAG and ceramide.<h4>Methods</h4>Sixteen overweight to obese adults (BMI 30.6 ± 0.8; 67.2 ± 4.0 years of age) with either impaired fasting glucose, or impaired glucose toleran ...[more]

PMID: 21327867

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Project description:Weight loss induced by decreased energy intake (diet) or exercise generally has favorable effects on insulin sensitivity and cardiometabolic risk. The variation in these responses to diet-induced weight loss with or without exercise, particularly in older obese adults, is less clear. The objectives of our study were to (1) examine the effect of weight loss with or without exercise on the variability of responses in insulin sensitivity and cardiometabolic risk factors and (2) to explore whether baseline phenotypic characteristics are associated with response. Sedentary older obese (BMI 36.3 ± 5.0 kg/m2) adults (68.6 ± 4.7 years) were randomized to one of 3 groups: health education control (HED); diet-induced weight loss (WL); or weight loss and exercise (WL + EX) for 6 months. Composite Z-scores were calculated for changes in insulin sensitivity (C_IS: rate of glucose disposal/insulin at steady state during hyperinsulinemic euglycemic clamp, HOMA-IR, and HbA1C) and cardiometabolic risk (C_CMR: waist circumference, triglycerides, and fasting glucose). Baseline measures included body composition (MRI), cardiorespiratory fitness, in vivo mitochondrial function (ATPmax; P-MRS), and muscle fiber type. WL + EX groups had a greater proportion of High Responders in both C_IS and C_CMR compared to HED and WL only (all p < 0.05). Pre-intervention measures of insulin (r = 0.60) and HOMA-IR (r = 0.56) were associated with change in insulin sensitivity (C_IS) in the WL group (p < 0.05). Pre-intervention measures of glucose (r = 0.55), triglycerides (r = 0.53), and VLDL (r = 0.53) were associated with change in cardiometabolic risk (C_CMR) in the WL group (p < 0.05), whereas triglycerides (r = 0.59) and VLDL (r = 0.59) were associated with C_CMR (all p < 0.05) in WL + EX. Thus, the addition of exercise to diet-induced weight loss increases the proportion of older obese adults who improve insulin sensitivity and cardiometabolic risk. Additionally, individuals with poorer metabolic status are more likely to experience greater improvements in cardiometabolic risk during weight loss with or without exercise.

Project description:BackgroundObesity is a risk factor for postmenopausal breast cancer incidence and premenopausal and postmenopausal breast cancer mortality, which may be explained by several metabolic and hormonal factors (sex hormones, insulin resistance, and inflammation) that are biologically related. Differential effects of dietary composition on weight loss and these metabolic factors may occur in insulin-sensitive vs. insulin-resistant obese women.ObjectiveTo examine the effect of diet composition on weight loss and metabolic, hormonal and inflammatory factors in overweight/obese women stratified by insulin resistance status in a 1-year weight loss intervention.Methods and resultsNondiabetic women who were overweight/obese (n=245) were randomly assigned to a lower fat (20% energy), higher carbohydrate (65% energy) diet; a lower carbohydrate (45% energy), higher fat (35% energy) diet; or a walnut-rich (18% energy), higher fat (35% energy), lower carbohydrate (45% energy) diet. All groups lost weight at follow-up (P<0.0001), with mean (SEM) percent loss of 9.2(1.1)% in lower fat, 6.5(0.9)% in lower carbohydrate, and 8.2(1.0)% in walnut-rich groups at 12months. The diet×time×insulin resistance status interaction was not statistically significant in the model for overall weight loss, although insulin sensitive women at 12months lost more weight in the lower fat vs. lower carbohydrate group (7.5kg vs. 4.3kg, P=0.06), and in the walnut-rich vs. lower carbohydrate group (8.1kg vs. 4.3kg, P=0.04). Sex hormone binding globulin increased within each group except in the lower carbohydrate group at 12months (P<0.01). C-reactive protein and interleukin-6 decreased at follow-up in all groups (P<0.01).ConclusionsFindings provide some support for differential effects of diet composition on weight loss depending on insulin resistance status. Prescribing walnuts is associated with weight loss comparable to a standard lower fat diet in a behavioral weight loss intervention. Weight loss itself may be the most critical factor for reducing the chronic inflammation associated with increased breast cancer risk and progression.

Project description:PurposeAn increasing number of studies have linked the severity of obstructive sleep apnea (OSA) with metabolic dysfunction. However, little is known about the lipid compartments (intramyocellular [IMCL] and extramyocellular [EMCL] lipids) inside the musculature in these patients. The present study was designed to investigate the IMCL and EMCL, biochemical data, and functional performance in patients with severe OSA, and to examine the correlations between intramuscular lipid contents and test variables.Participants and methodsTwenty patients with severe OSA (apnea-hypopnea index [AHI]: ≥30/h; body mass index [BMI]: 26.05±2.92) and 20 age- and BMI-matched controls (AHI <5/h) were enrolled. Proton magnetic resonance spectroscopy was used to measure the IMCL and EMCL of the right vastus lateralis muscle. Biochemical data, including levels of fasting plasma glucose, insulin, lipid profiles, and high-sensitivity C-reactive protein (hsCRP), were measured. Insulin resistance index (IR) was calculated using the homeostasis model assessment method. Performance tests included a cardiopulmonary exercise test and knee extension strength and endurance measurements.ResultsPatients with severe OSA had significantly (P<0.05) lower values of IMCL (14.1±5.4 AU) and EMCL (10.3±5.8 AU) compared to the control group (25.2±17.6 AU and 14.3±11.1 AU, respectively). Patients with severe OSA had significantly higher hsCRP, IR, and dyslipidemia compared with controls (all P<0.05). Furthermore, IMCL was negatively correlated with AHI, cumulative time with nocturnal pulse oximetric saturation lower than 90% (TSpO2<90%) (ρ=-0.35, P<0.05), IR (ρ=-0.40, P<0.05), glucose (ρ=-0.33, P<0.05), and insulin (ρ=-0.36, P<0.05), and positively correlated with lowest oximetric saturation (ρ=0.33, P<0.01).ConclusionSkeletal muscle dysfunction and metabolic abnormalities were observed in patients with OSA that did not have obesity. IMCL was positively correlated with aerobic capacity and muscular performance, but negatively correlated with AHI and IR. Large-scale clinical trials are required to explore the complicated mechanism among OSA, intramuscular metabolism, and insulin action.Clinical trial registrationClinicalTrials.gov Identifier: NCT00813852.

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Effects of weight loss and exercise on insulin resistance, and intramyocellular triacylglycerol, diacylglycerol and ceramide.

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Effects of weight loss and exercise on insulin resistance, and intramyocellular triacylglycerol, diacylglycerol and ceramide.

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