Melissa A. Reed

Mechanism for Improved Insulin Sensitivity after Gastric Bypass Surgery

CONTEXT Surgical treatments of obesity have been shown to induce rapid and prolonged improvements in insulin sensitivity. OBJECTIVE The aim of the study was to investigate the effects of gastric bypass surgery and the mechanisms that explain the improvement in insulin sensitivity. DESIGN We performed a cross-sectional, nonrandomized, controlled study. SETTING This study was conducted jointly between the Departments of Exercise Science and Physiology at East Carolina University in Greenville, North Carolina. SUBJECTS Subjects were recruited into four groups: 1) lean [body mass index (BMI) < 25 kg/m(2); n = 93]; 2) weight-matched (BMI = 25 to 35 kg/m(2); n = 310); 3) morbidly obese (BMI > 35 kg/m(2); n = 43); and 4) postsurgery patients (BMI approximately 30 kg/m(2); n = 40). Postsurgery patients were weight stable 1 yr after surgery. MAIN OUTCOME MEASURES Whole-body insulin sensitivity, muscle glucose transport, and muscle insulin signaling were assessed. RESULTS Postsurgery subjects had insulin sensitivity index values that were similar to the lean and higher than morbidly obese and weight-matched control subjects. Glucose transport was higher in the postsurgery vs. morbidly obese and weight-matched groups. IRS1-pSer(312) in the postsurgery group was lower than morbidly obese and weight-matched groups. Inhibitor kappaBalpha was higher in the postsurgery vs. the morbidly obese and weight-matched controls, indicating reduced inhibitor of kappaB kinase beta activity. CONCLUSIONS Insulin sensitivity and glucose transport are greater in the postsurgery patients than predicted from the weight-matched group, suggesting that improved insulin sensitivity after bypass is due to something other than, or in addition to, weight loss. Improved insulin sensitivity is related to reduced inhibitor of kappaB kinase beta activity and enhanced insulin signaling in muscle.

Lipid Partitioning, Incomplete Fatty Acid Oxidation, and Insulin Signal Transduction in Primary Human Muscle Cells: Effects of Severe Obesity, Fatty Acid Incubation, and Fatty Acid Translocase/CD36 Overexpression

CONTEXT Intracellular lipid partitioning toward storage and the incomplete oxidation of fatty acids (FA) have been linked to insulin resistance. OBJECTIVE To gain insight into how intracellular lipid metabolism is related to insulin signal transduction, we examined the effects of severe obesity, excess FA, and overexpression of the FA transporter, FA translocase (FAT)/CD36, in primary human skeletal myocytes. DESIGN, SETTING, AND PATIENTS Insulin signal transduction, FA oxidation, and metabolism were measured in skeletal muscle cells harvested from lean and severely obese women. To emulate the obesity phenotype in our cell culture system, we incubated cells from lean individuals with excess FA or overexpressed FAT/CD36 using recombinant adenoviral technology. RESULTS Complete oxidation of FA was significantly reduced, whereas total lipid accumulation, FA esterification into lipid intermediates, and incomplete oxidation were up-regulated in the muscle cells of severely obese subjects. Insulin signal transduction was reduced in the muscle cells from severely obese subjects compared to lean controls. Incubation of muscle cells from lean subjects with lipids reduced insulin signal transduction and increased lipid storage and incomplete FA oxidation. CD36 overexpression increased FA transport capacity, but did not impair complete FA oxidation and insulin signal transduction in muscle cells from lean subjects. CONCLUSIONS Cultured myocytes from severely obese women express perturbations in FA metabolism and insulin signaling reminiscent of those observed in vivo. The obesity phenotype can be recapitulated in muscle cells from lean subjects via exposure to excess lipid, but not by overexpressing the FAT/CD36 FA transporter.

Lipid-induced insulin resistance is prevented in lean and obese myotubes by AICAR treatment.

The molecular mechanisms of obesity-associated insulin resistance are becoming increasingly clear, and the effects of various lipid molecules, such as diacylglycerol and ceramide, on the insulin signal are being actively explored. To better understand the divergent response to lipid exposure between lean and obese, we incubated primary human muscle cells from lean [body mass index (BMI) <25 kg/m(2)] and morbidly obese (BMI >40 kg/m(2)) subjects with the saturated fatty acid palmitate. Additionally, given that AMPK-activating drugs are widely prescribed for their insulin-sensitizing effects, we sought to determine whether 5-aminoimidazole-4-carboxamide 1-beta-D-ribofuranoside (AICAR)-stimulated AMPK activation could prevent or reverse the deleterious effects of lipid on insulin signaling. We found that a 1-h palmitate incubation in lean myotubes reduced (P < 0.05) insulin-stimulated phosphoprotein kinase B (Akt), Akt substrate 160 (AS160), and inhibitory factor kappaBalpha (IkappaBalpha) mass, all of which were prevented with AICAR inclusion. With a longer incubation, we observed that myotubes from morbidly obese individuals appear to be largely resistant to the detrimental effects of 16 h lipid exposure as was evident, in contrast to the lean, by the absence of a reduction in insulin-stimulated insulin receptor substrate (IRS)-1 Tyr phosphorylation, phospho-Akt, and phospho-AS160 (P < 0.05). Furthermore, 16 h lipid exposure significantly reduced IkappaBalpha levels and increased phosphorylation of c-Jun NH(2)-terminal kinase (JNK) and IRS1-Ser(312) in lean myotubes only (P < 0.05). Despite a divergent response to lipid between lean and obese myotubes, AICAR inclusion improved insulin signaling in all myotubes. These findings suggest an important role for regular exercise in addition to offering a potential mechanism of action for oral AMPK-activating agents, such as thiazolidinediones and metformin.

Effect of short-term exercise training on intramyocellular lipid content

The purpose of this study was to investigate the influence of exercise training on intramyocellular lipid (IMCL) content and test the hypothesis that the effect of endurance-oriented exercise training on IMCL is dependent on characteristics of the population studied. Lean (N = 11, body mass index (BMI) = 22.2 ± 0.7 kg·m⁻²), obese (N = 14, BMI = 38.8 ± 1.7 kg·m⁻²), and type 2 diabetic (N = 9, BMI = 35.5 ± 2.5 kg·m⁻²) participants were examined before and after 10 consecutive days of endurance-oriented (60 min·day⁻¹ at ~70% [Formula: see text]O(2peak)) exercise training. IMCL and muscle glycogen were measured by Oil-Red-O and periodic acid - Schiff staining, respectively. The results indicated that IMCL was elevated (p < 0.05) in the obese and diabetic groups compared with the lean subjects prior to training. After training, IMCL content decreased (-35%) in the participants with type 2 diabetes; there were no changes in IMCL in the lean or obese groups. Muscle glycogen content was lower in the diabetic subjects than in the lean subjects both before and after training. These data indicate that changes in IMCL with exercise training do not exhibit a universal response but rather depend on the metabolic status of the population studied.

The Effects of Pedometers on Body Weight and Metabolic Factors in Patients with Prediabetes: 918 Board #179 May 30 3

Sedentary behavior, increased total body weight, elevated blood glucose levels and hyperlipidemia increase the risk of prediabetes. Individuals diagnosed with prediabetes (fasting blood glucose (FBG) between 100125mg/dL) are recommended to perform a minimum of 150 minutes of physical activity (PA) per week and decrease total body weight by 7% to reduce the likelihood of developing type 2 diabetes. However, there is little known about the role of pedometers with regards to a Diabetes Prevention Program (DPP) PURPOSE: To determine if pedometer use could aid in the reduction of total body weight, cholesterol, and blood glucose levels as a part of the Centers for Disease Control National DPP. METHODS: Body weight, FBG and lipids (total cholesterol, high-density lipoproteins (HDL) and low-density lipoproteins (LDL)) were measured prior to the start of the DPP and 16 weeks following the intervention. All participants were either diagnosed as prediabetic or at risk for prediabetes based on the CDC screening tool. The pedometer group (PG) (n=9) received pedometers and the control group (CG) (n=8) did not. All participants received the same educational sessions that explained dietary changes and strategies to increase PA. The PG was asked to wear a pedometer on their belt for all waking hours of the day, seven days a week, for sixteen weeks. At each weekly DPP meeting, step counts from pedometers were recorded and pedometers were reset and returned to the participants. A 2x2 ANOVA was performed to examine differences. RESULTS: The PG experienced significant (p<0.05) weight loss from pre to post-test (186.2lbs + 9.7 to 180.7 + 8.9) while the control group did not (191.3lbs + 16.8l to 190.1 + 17.0). Interestingly, HDL significantly decreased from pre to post-test (p>0.05) in the PD group (58.1mg/dL + 4.0 to 54.1mg/dL + 3.6) while the CG remained unchanged (50.9mg/dL + 5.1 to 50.5mg/dL + 4.8). There were no differences between any other variables. CONCLUSIONS: It appears that the addition of pedometers into the DPP can contribute positively to weight loss. It is possible participants experienced a sense of greater accountability due to the added tracking tool. Further research and a larger participation population is needed to elucidate the mechanisms that contribute to the changes in body weight and lipid profile.

The Effects of Testosterone Boosters on Testosterone, Strength, and Body Composition in Young Trained Males: 234 Board #71 June 1, 9: 30 AM - 11: 00 AM.

Athletes frequently use nutritional supplementation to improve physical performance. Herbal testosterone boosters claim to increase testosterone and maximize strength gains and lean body mass. PURPOSE: To investigate if testosterone, strength and lean body mass are increased in young trained males taking an herbal testosterone supplement compared to a placebo during a 6-week resistance training period. METHODS: Participants were randomly assigned to the placebo (pl) group (n = 6) or the experimental (exp) group (n = 5). Participants and researchers were blinded to group assignments. Blood and saliva samples were collected in the fasted state prior to the intervention (pre), 3 weeks (mid) and 6 weeks (post) to measure testosterone. 1RM squat and bench press and body composition were measured at all three time points. Participants supplemented with the herbal testosterone booster or 500mg of oregano in capsule form twice daily. RESULTS: No significant difference was detected between groups for % change in squat (p = 0.792) or bench press (p = 0.429). There was no significant difference between groups for unbound serum testosterone % change from pre to post (p = 1.000) as well as between groups for unbound serum testosterone concentrations (pre p = 0.429, 3w p = 0.622, post p = 0.537). No significant difference occurred between groups for total saliva testosterone % change from pre to post (exp = 16.69 ± 21.22%, pl = 40.48 ± 38.17%; p = 0.329). A significant difference was detected between groups post -test saliva testosterone concentration (exp 728.82 ± 199.37 ng·dl-1, pl 1153.54 ± 357.11 ng·dl-1; p = 0.030) as well as for % weight change (WT%) for the exp group compared to the pl group from pre to mid (p = 0.004, exp mean WT % change -1.44 ± 0.288%. pl mean WT % change 1.76 ± 1.39 %; p = 0.004). CONCLUSION: It appears that supplementation with a testosterone booster during a resistance training intervention does not increase testosterone, strength or lean body mass when compared to a placebo.