Michael G. Flynn

Exercise training-induced lowering of inflammatory (CD14+CD16+) monocytes: a role in the anti-inflammatory influence of exercise?

Exercise training or higher levels of physical activity are known to exert anti‐inflammatory effects. CD14+CD16+ monocytes are potent producers of inflammatory proteins, and elevated levels of these “inflammatory” monocytes have been implicated in disease development. Little is known about the influence of exercise training on this cell population. On the basis of their physical activity pattern, male and female subjects, 65–80 years old, were assigned to a physically active (PA; n=15) or inactive (PI; n=15) group. The PI group performed 12 weeks (3 days/week) of endurance (20 min at 70–80% heart‐rate reserve) and resistance exercise training (eight exercises, two sets at 70–80% of one repetition maximum). Subjects in the PA group maintained their habitual activity level. Flow cytometry was used to determine monocyte phenotype and monocyte TLR4 expression. ELISAs were used to measure whole blood, LPS‐stimulated TNF‐α production, and serum C‐reactive protein (CRP). At baseline, the PA group had a lower percentage of CD14+CD16+ monocytes and lower unstimulated production of TNF‐α than the PI group. CD14+CD16+ monocyte percentage and 1 ng/ml LPS‐stimulated TNF‐α production were reduced after the PI group underwent 12 weeks of exercise training. PI subjects also had higher TLR4 expression on classical monocytes, but there were no significant exercise training‐induced changes in monocyte TLR4 expression. The PA group had significantly lower serum CRP than the PI group. Physical activity was associated with lower CD14+CD16+ monocyte percentage and LPS‐stimulated TNF‐α production. Exercise training‐induced reductions in CD14+CD16+ monocytes may contribute to the anti‐inflammatory effects of exercise training.

Fatigue during high-intensity intermittent exercise: application to bodybuilding.

AbstractResistance exercise is an activity performed by individuals interested in competition, those who wish to improve muscle mass and strength for other sports, and for individuals interested in improving their strength and physical appearance. In this review we present information suggesting that phosphocreatine depletion, intramuscular acidosis and carbohydrate depletion are all potential causes of the fatigue during resistance exercise. In addition, recommendations are provided for nutritional interventions, which might delay muscle fatigue during this type of activity.

State of the Art Reviews: The Anti-Inflammatory Actions of Exercise Training

The list of diseases with a known inflammatory etiology is growing. Cardiovascular disease, osteoporosis, diabetes, geriatric cachexia, and Alzheimers disease have all been shown to be linked to or exacerbated by aberrantly regulated inflammatory processes. Nevertheless, there is mounting evidence that those who are physically active, or who become physically active, have a reduction in biomarkers associated with chronic inflammation. There was strong early consensus that exercise-induced reductions in inflammation were explained by body mass index or body fatness, but recent studies provide support for the contention that exercise has body fat—independent anti-inflammatory effects. With few exceptions, the anti-inflammatory effects of exercise appear to occur regardless of age or the presence of chronic diseases. What remains unclear are the mechanisms by which exercise training induces these anti-inflammatory effects, but there are several intriguing possibilities, including release of endogenous products, such as heat shock proteins; selective reduction of visceral adipose tissue mass or reducing infiltration of adipocytes by macrophages; shift in immune cell phenotype; cross-tolerizing effects; or exercise-induced shifts in accessory proteins of toll-like receptor signaling. However, future research endeavors are likely to uncover additional potential mechanisms, and it could be some time before functional mechanisms are made clear. In summary, the potential anti-inflammatory influences of exercise training may provide a low-cost, readily available, and effective treatment for low-grade systemic inflammation and could contribute signifiecantly to the positive effects of exercise training on chronic disease.

Protein Intake during Energy Restriction: Effects on Body Composition and Markers of Metabolic and Cardiovascular Health in Postmenopausal Women

Objective: The primary aim of this study was to assess the effects of dietary protein intake on energy restriction (ER)-induced changes in body mass and body composition. Clinical markers of metabolic and cardiovascular diseases were also measured. Design: 54 postmenopausal women, age 58 ± 2 y, body mass index 29.6 ± 0.8 kg/m2, were assigned to one of four groups. For 9 weeks, three ER groups ate a 1000 kcal/d lacto-ovo vegetarian basal diet plus 250 kcal/d of either beef (BEEF, n = 14), chicken (CHICKEN, n = 15), or carbohydrate/fat foods (CARB (lacto-ovo), n = 14), while a control group (CON, n = 11) consumed their habitual diets. Results: Energy intake was lower in the ER groups compared to CON (BEEF, 1114 ± 155 kcal/d, CHO: PRO: FAT, 46:24:30 % of energy intake; CHICKEN, 1098 ± 203 kcal/d, 51:25:24; CARB 1158 ± 341 kcal/d, 59:17:24; CON, 1570 ± 633 kcal/d, 47:20:33), but did not differ among ER groups. For all ER subjects combined, body mass (−6.7 ± 2.4 kg, 9 %), fat mass (−4.6 ± 1.9 kg, 13 %), and fat-free mass (−2.1 ± 1.1 kg, 5 %) decreased. These responses did not differ among the ER groups, except for body mass (CHICKEN −7.9 ± 2.6 kga; BEEF −6.6 ± 2.7 kga,b; CARB −5.6 ± 1.8 kgb; CON −1.2 ± 1.2 kgc; values with a difference superscript differ, p < 0.05). From PRE (week 0) to POST (week 9), total and LDL cholesterol decreased ∼12%, with no differences among groups. Triacylglycerol, HDL cholesterol, C-reactive protein (CRP), glucose, insulin, leptin, and adiponectin were not changed over time or differentially affected by diet. Conclusions: Overweight postmenopausal women can achieve significant weight loss and comparable short-term improvements in body composition and lipid-lipoprotein profile by consuming either a moderate-protein (25% of energy intake) poultry- or beef-containing diet or a lacto-ovo vegetarian protein (17% of energy intake) diet.

Impact of vitamin D supplementation during a resistance training intervention on body composition, muscle function, and glucose tolerance in overweight and obese adults.

BACKGROUND & AIMS The impact of vitamin D supplementation in overweight and obese adults during resistance training on body composition, muscle function, and glucose tolerance was investigated. METHODS Twenty-three overweight and obese (age: 26.1±4.7 y; BMI: 31.3±3.2 kg/m(2); 25-hydroxyvitamin D: 19.3±7.2 ng/mL) adults were recruited for participation in a double-blind, placebo-controlled trial. Participants were randomly divided into vitamin D (VitD, 4000 IU/d; 5 females, 5 males) and placebo (PL; 7 females, 6 males) groups. Both groups completed 12 weeks of resistance training. 25-hydroxyvitamin D, parathyroid hormone, body composition, and glucose tolerance were assessed at baseline and 12 weeks. Muscle function (strength and power) was assessed at baseline, 4, 8, and 12 weeks. RESULTS During the intervention, 25-hydroxyvitamin D increased and parathyroid hormone decreased in the VitD group (P<0.05). Peak power was significantly increased at 4 weeks in the VitD group only (P<0.05). Regression analysis revealed an inverse association between the change in 25-hydroxyvitamin D with the change in waist-to-hip ratio (R(2)=0.205, P=0.02). No other improvements were observed with supplementation. CONCLUSIONS Vitamin D supplementation in overweight and obese adults during resistance training induced an early improvement in peak power, and elevated vitamin D status was associated with reduced waist-to-hip ratio. CLINICAL TRIAL REGISTRATION NUMBER NCT01199926.

Adding exercise to rosuvastatin treatment: influence on C-reactive protein, monocyte toll-like receptor 4 expression, and inflammatory monocyte (CD14+CD16+) population.

Statin treatment and exercise training can reduce markers of inflammation when administered separately. The purpose of this study was to determine the effect of rosuvastatin treatment and the addition of exercise training on circulating markers of inflammation including C-reactive protein (CRP), monocyte toll-like receptor 4 (TLR4) expression, and CD14+CD16+ monocyte population size. Thirty-three hypercholesterolemic and physically inactive subjects were randomly assigned to rosuvastatin (R) or rosuvastatin/exercise (RE) groups. A third group of physically active hypercholesterolemic subjects served as a control (AC). The R and RE groups received rosuvastatin treatment (10 mg/d) for 20 weeks. From week 10 to week 20, the RE group also participated in an exercise training program (3d/wk). Measurements were made at baseline (Pre), week 10 (Mid), and week 20 (Post), and included TLR4 expression on CD14+ monocytes and CD14+CD16+ monocyte population size as determined by 3-color flow cytometry. Serum CRP was quantified by enzyme-linked immunosorbent assay. TLR4 expression on CD14+ monocytes was higher in the R group at week 20. When treatment groups (R and RE) were combined, serum CRP was lower across time. Furthermore, serum CRP and inflammatory monocyte population size were lower in the RE group compared with the R group at the Post time point. When all groups (R, RE, and AC) were combined, TLR4 expression was greater on inflammatory monocytes (CD14+CD16+) compared with classic monocytes (CD14+CD16⁻) at all time points. In conclusion, rosuvastatin may influence monocyte inflammatory response by increasing TLR4 expression on circulating monocytes. The addition of exercise training to rosuvastatin treatment further lowered CRP and reduced the size of the inflammatory monocyte population, suggesting an additive anti-inflammatory effect of exercise.

Adding exercise training to rosuvastatin treatment: influence on serum lipids and biomarkers of muscle and liver damage

Statin treatment and exercise training can improve lipid profile when administered separately. The efficacy of exercise and statin treatment combined, and its impact on myalgia and serum creatine kinase (CK) have not been completely addressed. The purpose of this study was to determine the effect of statin treatment and the addition of exercise training on lipid profile, including oxidized low-density lipoprotein (oxLDL), and levels of CK and alanine transaminase. Thirty-one hypercholesterolemic and physically inactive subjects were randomly assigned to rosuvastatin (R) or rosuvastatin/exercise (RE) group. A third group of physically active hypercholesterolemic subjects served as an active control group (AC). The R and RE groups received rosuvastatin treatment (10 mg/d) for 20 weeks. From week 10 to week 20, the RE group also participated in a combined endurance and resistive exercise training program (3 d/wk). Lipid profile was determined for all subjects at week 0 (Pre), week 10 (Mid), and week 20 (Post). The CK and alanine transaminase levels were measured at the same time points in the RE and R groups and 48 hours after the first and fifth exercise bout in the RE group. Each RE subject was formally queried about muscle fatigue, soreness, and stiffness before each training session. Total, LDL, and oxLDL cholesterol was lower in the RE and R groups at Mid and Post time points when compared with Pre. Oxidized LDL was lower in the RE group compared with the R group at the Post time point. When treatment groups (R and RE) were combined, high-density lipoprotein levels were increased and triglycerides decreased across time. Creatine kinase increased in the RE group 48 hours after the first exercise bout, but returned to baseline levels 48 hours after the fifth exercise bout. Rosuvastatin treatment decreased total, LDL, and oxLDL cholesterol. The addition of an exercise training program resulted in a further decrease in oxLDL. There was no abnormal sustained increase in CK or reports of myalgia after the addition of exercise training to rosuvastatin treatment.

Effects of hormone replacement therapy on selected indices of immune function in postmenopausal women

The purpose of this study was to examine the effects of long-term hormone replacement therapy (HRT) on selected indices of resting immune function in postmenopausal women. Postmenopausal women aged 54–66 were divided into two groups, those taking HRT (n = 17) and controls (n = 19). Blood samples were obtained and analyzed for mononuclear cell numbers, lymphocyte proliferation (LP) and natural cell-mediated cytotoxicity (NCMC). There were no significant differences between groups for mononuclear cell numbers. LP was significantly higher for HRT, while NCMC was significantly lower for HRT. HRT is currently being prescribed to postmenopausal women for prevention of a variety of medical conditions including osteoporosis, cardiovascular disease, stroke, and Alzheimer’s disease yet HRT is often associated with altered immune parameters. In this study, women taking HRT had increased lymphocyte blastogenesis and decreased NCMC compared to controls.

Exercise Training Modifies Ghrelin and Adiponectin Concentrations and Is Related to Inflammation in Older Adults

The purpose of this study was to observe exercise training-induced effects on adiponectin, leptin, and ghrelin. Twenty-nine older, healthy participants were classified as physically active (comparison group: N = 15, 70.9 ± 1.2 years) or physically inactive (exercise group: N = 14, 70.5 ± 1.4 years). Exercise group participants completed 12 weeks of combined aerobic and resistance exercise training, whereas comparison group participants maintained their current level of exercise and served as a physically active comparison group. Monocyte phenotype, as well as serum ghrelin, leptin, adiponectin, and soluble tumor necrosis factor receptor II were analyzed prior to and following the 12-week period. Ghrelin and adiponectin increased 47% and 55%, respectively, in exercise group participants following exercise training. Percent change in ghrelin (post and pre) was negatively correlated with the percent change in CD14+CD16+ monocytes (post and pre) in exercise group participants. Despite no changes in body mass, these data contribute to evidence for the anti-inflammatory effects of exercise.

Cross training: indices of training stress and performance

Twenty well-trained runners (VO2max 4.6+/-0.5 L x min[-1]) were age and ability matched and assigned to either a cross training (CT) or run only group (RT). All subjects maintained normal running distance and intensity for 6 wk and reported for three additional training sessions per week. These workouts were performed outdoors on a 400-m track or measured road course (RT) or on a bicycle ergometer (CT). The sessions were as follows: (work x rest(-1) ratio = 1): 5 x 5 min at >95% VO2max/peak (Monday), 50-60 min at 70% VO2max/peak (Wednesday), and 3 x 2.5 min at >105% VO2max/peak, plus 6 x 1.25 min at >115% VO2max/peak (Friday). Subjects were tested before (PRE), after 3 wk (MID), and after 6 wk (POST) of intensified training. Blood samples were obtained from RT, CT, and ten controls (CON) at each time point (0600 h). Runners also completed a 10-min submaximal run at the same absolute intensity (velocity to elicit 75% of initial V02max) during which heart rate, RPE, and VO2 were measured. Each runner then completed a simulated 5-km race (time trial) on a treadmill. Total testosterone (TT), free testosterone (FT), cortisol (C), and creatine kinase activity (CK) were determined. Running economy was similar between RT and CT; however, RPE decreased significantly at MID and POST compared with that at PRE (P < 0.05; time effect). There were no significant differences among groups for TT, FT, or CK, but C was significantly lower in CON than in RT and CT. Performance was significantly faster (P < 0.05; time effect) in the 5-km race at MID (1076.1+/-81.4 s) and POST (1068.6+/-83.9) compared with PRE (1096.6+/-79.5) but was not different between CT and RT. In conclusion, RT and CT responded similarly to 6 wk of increased training, and both groups improved 5-km performance to a similar extent.