Intramuscular lipid oxidation and obesity

There is an accumulating amount of evidence indicating that lipid oxidation is depressed in the skeletal muscle of obese individuals. Decrements in fatty acid oxidation (FAO) have been reported with obesity in models ranging from whole body measurements to isolated skeletal muscle preparations as well as in myotubes raised in culture. This reduction appears to be associated with a depression in the activities of enzymes involved in various steps of lipid oxidation, which subsequently partitions lipid entering the cell toward storage. The defect in FAO in skeletal muscle may be critical in relation to health, as a reduction in the capacity for lipid oxidation could directly or indirectly contribute to the insulin resistance commonly evident with obesity. Although less characterized, a decrement in FAO has also been linked with weight gain, which suggests that this characteristic may be an integral aspect leading to the obese state. In terms of intervention, weight loss does not seem to correct the defect in FAO with obesity. This review will provide evidence supporting a reduction in muscle FAO with obesity. Originally published AJP - Regulatory, Integrative and Comparative Physiology 294(4) 2009

Is There a Metabolic Program in the Skeletal Muscle of Obese Individuals?

Severe obesity (BMI ≥ 40 kg/m2) is associated with multiple defects in skeletal muscle which contribute to insulin resistance and a reduction in fatty acid oxidation (FAO) in this tissue. These metabolic derangements are retained in human skeletal muscle cells raised in culture. Together, these findings are indicative of a dysfunctional global metabolic program with severe obesity which is of an epigenetic or genetic origin. Weight loss via gastric bypass surgery can “turn off” and/or correct components of this metabolic program as insulin sensitivity is restored; however, the impairment in FAO in skeletal muscle remains evident. Physical activity can improve FAO and insulin action, indicating that this patient population is not exercise resistant and that exercise offers a pathway to circumvent the abnormal program. Findings presented in this review will hopefully increase the understanding of and aid in preventing and/or treating the severely obese condition

Effects of aerobic training with and without weight loss on insulin sensitivity and lipids

Purpose: The purpose of this study is to evaluate the effect of exercise training with modest or greater weight loss (≥3%) or not (<3%) on insulin sensitivity, lipoprotein concentrations, and lipoprotein particle size in overweight and obese participants. Methods: Adults (N = 163, body mass index: 25–37 [kg/m2]) participated in 8 months of exercise training. Insulin sensitivity, lipid concentrations, lipid particle size and other cardiometabolic variables were measured at baseline and follow-up. Participants were categorized by whether they achieved at least modest weight loss (≥ 3%) or not (<3%) following the intervention. Results: A greater improvement in insulin sensitivity was observed in adults performing exercise training with at least modest weight loss (2.2 mU·l-1 ·min -1, CI: 1.5 to 2.8) compared to those who did not (0.8 mU·l-1 ·min -1, CI: 0.5 to 1.2). Similar results were observed for acute insulin response, triglycerides, non-HDL cholesterol concentration, low density lipoprotein (LDL) particle size and high density lipoprotein (HDL) particle size (p<0.05), when all exercise groups were combined. No significant results across weight loss categories were observed for LDL, HDL, glucose, or insulin levels. Conclusion: The present study suggests that aerobic exercise combined with at least modest weight loss leads to greater improvements in insulin sensitivity, triglycerides as well as other non-traditional lipid risk factors (non-HDL cholesterol, HDL/LDL particle size). Clinicians should advocate patients who are overweight/obese to exercise and obtain modest weight loss for improved cardiovascular benefits

Relationships between Adipose Tissue and Cytokine Responses to a Randomized Controlled Exercise Training Intervention

Adipose-derived cytokines play a prominent role in mediating the metabolic consequences of obesity and excess body fat. Given this, we hypothesized that alterations in adipose tissue stores incurred with exercise training would be reflected in changes in systemic cytokine concentrations. The Studies of Targeted Risk Reduction Intervention through Defined Exercise (STRRIDE), where pronounced changes in adipose tissue stores were observed in the absence of significant changes in dietary intake, provided an ideal setting in which to test this hypothesis. Participants were randomized to six months of inactivity or one of three types of aerobic exercise training regimens: low-amount-moderate- intensity, low-amount-vigorous-intensity, and high-amount-vigorous-intensity. Plasma samples were collected at baseline and two weeks after cessation of six months of exercise training or inactivity. In 189 participants, concentrations of seventeen cytokines were measured using Bio-Plex Cytokine Assays (BioRad, CA); ten additional cytokines were measured in sixty of these subjects. Of all cytokines tested, the only concentration changes that approached statistical significance were those for granulocyte monocyte-colony stimulating factor and vascular endothelial growth factor, which appeared to increase with training in the low-amount-high-intensity group only (P<0.05 for both cytokines). No response to exercise training was noted for any additional cytokine in any of the groups. No relationships were observed between changes in cytokine concentrations and changes in fat mass or other measures of body habitus. In contradiction to our hypothesis, despite significant alterations in body composition, exercise training produced limited cytokine responses. Originally published Metabolism, Vol. 57, No. 4, Apr 200

Roux-en-Y Gastric Bypass Surgery Regulates Mitochondrial Dynamics Proteins in Primary Human Myotubes Derived from Severely Obese Humans

Mitochondrial dynamics including mitochondrial fission (e.g., Dynamin-related protein 1 (Drp1) and Fission 1 (Fis1)) and fusion (e.g., Mitofusin 2 (MFN 2)) regulates mitochondrial homeostasis. Defects in mitochondrial dynamics are suggested to contribute to skeletal muscle mitochondrial dysfunction and insulin resistance associated with severe obesity. Roux-en-Y gastric bypass (RYGB) surgery markedly improves metabolic health as indicated by enhanced substrate oxidation and insulin action in skeletal muscle. However, the underlying cellular mechanisms responsible for these are unclear and could possibly be due to the improvement of mitochondrial dynamics. PURPOSE: The purpose of this study was to determine whether RYGB surgery improves mitochondria dynamics proteins in primary human myotubes from severely obese humans. METHODS: Primary skeletal muscle cells were isolated from muscle biopsies obtained from six lean subjects (BMI = 23.4 ± 0.6 kg/m2) and six RYGB patients prior to, 1-month and 7-months after surgery (BMI = 50.2 ± 2.0, 43.2 ± 2.8 and 35.7 ± 2.2 kg/m2, respectively) and were differentiated to myotubes. On day 7 of differentiation, myotubes were harvested for further assessing the expressions of mitochondria dynamics proteins. RESULTS: Before surgery, Drp1Ser616 phosphorylation and Fis1 expression were significantly higher in myotubes derived from severely obese patients when compared to lean controls (41% and 26%, respectively, P \u3c 0.05). While there were no improvements at 1-month post-surgery, Drp1Ser616 phosphorylation and Fis1 expression were significantly decreased in myotubes from severely obese humans at 7-months post-surgery (Pre vs. 7-months post: 0.046 ± 0.004 vs. 0.035 ± 0.003; 0.023 ± 0.008 vs. 0.014 ± 0.003 AU; respectively, P \u3c 0.05), and not statistically different from lean controls. However, MFN2 expression did not change post-surgery in comparison to pre-surgery. CONCLUSION: These data suggest that RYGB surgery reduces obesity-induced rise in mitochondrial fission, but not fusion in primary human myotubes derived from severely obese humans

Dietary carbohydrate intake and high sensitivity C reactive protein in at-risk women and men

Background— The quality and quantity of dietary carbohydrate intake, measured as dietary glycemic load (GL), is associated with a number of cardiovascular disease (CVD) risk factors and, in healthy young women, is related to increased high sensitivity C-reactive protein (hsCRP) concentrations. Our objective was to determine if GL is related to hsCRP and other measures of CVD risk in a population of sedentary, overweight, dyslipidemic middle-aged women and men enrolled in an exercise intervention trial (STRRIDE). Methods— This was a cross-sectional evaluation of the relationships between measures of dietary carbohydrate intake, calculated from food frequency questionnaire data, and CVD risk factors, including plasma hsCRP, measured in 171 subjects. Results— After adjusting for energy intake, GL and other measures of carbohydrate intake were not independently related to hsCRP (P>0.05 for all). In analyses performed separately for each gender, only the quantity of carbohydrate intake was independently related to hsCRP (R2=0.28; P<0.04), and this relationship was present for women but not for men. The strongest relationship identified between GL and any CVD risk factor was for cardiorespiratory fitness (R2=0.12; P<0.02); an elevated GL was associated with a lower level of fitness in all subjects, and this relationship persisted even when the findings were adjusted for energy intake and gender (R2=0.48; P<0.03). Conclusions— In middle-aged, sedentary, overweight to mildly obese, dyslipidemic individuals, consuming a diet with a low GL is associated with better cardiorespiratory fitness. Our findings suggest that the current literature relating carbohydrate intake and hsCRP should be viewed with skepticism, especially in the extension to at-risk populations that include men. Originally published American Heart Journal, Vol. 154, No. 5, Nov 200

Effect of exercise intensity and volume on persistence of insulin sensitivity during training cessation

Effect of exercise intensity and volume on persistence of insulin sensitivity during training cessation. J Appl Physiol 106: 1079â 1085, 2009. First published February 5, 2009; doi:10.1152/japplphysiol.91262.2008. The purpose of this study was to determine whether exercise prescriptions differing in volume or intensity also differ in their ability to retain insulin sensitivity during an ensuing period of training cessation. Sedentary, overweight/obese subjects were assigned to one of three 8-mo exercise programs: 1) low volume/moderate intensity [equivalent of 12 miles/wk, 1,200 kcal/wk at 40-55% peak O2 consumption (VO2peak), 200 min exercise/wk], 2) low volume/vigorous intensity (12 miles/wk, 1,200 kcal/wk at 65-80% VO2peak, 125 min/wk), and 3) high volume/vigorous intensity (20 miles/wk, 2,000 kcal/wk at 65-80% VO2peak, 200 min/wk). Insulin sensitivity (intravenous glucose tolerance test, SI) was measured when subjects were sedentary and at 16-24 h and 15 days after the final training bout. SI increased with training compared with the sedentary condition (P less than or equal to 0.05) at 16-24 h with all of the exercise prescriptions. SI decreased to sedentary, pretraining values after 15 days of training cessation in the low-volume/vigorous-intensity group. In contrast, at 15 days SI was significantly elevated compared with sedentary (P less than or equal to 0.05) in the prescriptions utilizing 200 min/wk (low volume/moderate intensity, high volume/vigorous intensity). In the high-volume/vigorous-intensity group, indexes of muscle mitochondrial density followed a pattern paralleling insulin action by being elevated at 15 days compared with pretraining; this trend was not evident in the low-volume/moderateintensity group. These findings suggest that in overweight/obese subjects a relatively chronic persistence of enhanced insulin action may be obtained with endurance-oriented exercise training; this persistence, however, is dependent on the characteristics of the exercise training performed