Tongjian You

Behavioural treatments for chronic systemic inflammation: effects of dietary weight loss and exercise training

PERSISTENT LOW-GRADE INFLAMMATION, as indicated by higher circulating levels of inflammatory mediators such as C-reactive protein, interleukin-6 and tumour necrosis factor-α, is a strong risk factor for several chronic diseases. There are data indicating that decreasing energy intake and increasing physical activity may be effective therapies for reducing overall inflammation. Evidence is strong that circulating levels of inflammatory markers are elevated with total and abdominal obesity, possibly owing to a higher secretion rate of cytokines by adipose tissue in obese people. Moreover, very-low-energy dietary weight loss reduces both circulating markers of inflammation and adipose-tissue cytokine production. Data from several large population-based cohorts show an inverse association between markers of systemic inflammation and physical activity or fitness status; small-scale intervention studies support that exercise training diminishes inflammation. Dietary weight loss plus exercise is likely more effective than weight reduction alone in reducing inflammation. To date, data from randomized, controlled trails designed to definitively test the effects of weight loss or exercise training, or both, on inflammation are limited. Future studies are required to define the amount of weight loss needed for clinically meaningful reductions of inflammation; in addition, fully powered and controlled studies are necessary to clarify the effect of exercise training on chronic, systemic inflammation.

Effect of exercise intensity on abdominal fat loss during calorie restriction in overweight and obese postmenopausal women: a randomized, controlled trial

BACKGROUND Exercise intensity may affect the selective loss of abdominal adipose tissue. OBJECTIVE This study showed whether aerobic exercise intensity affects the loss of abdominal fat and improvement in cardiovascular disease risk factors under conditions of equal energy deficit in women with abdominal obesity. DESIGN This was a randomized trial in 112 overweight and obese [body mass index (in kg/m(2)): 25-40; waist circumference >88 cm], postmenopausal women assigned to one of three 20-wk interventions of equal energy deficit: calorie restriction (CR only), CR plus moderate-intensity aerobic exercise (CR + moderate-intensity), or CR plus vigorous-intensity exercise (CR + vigorous-intensity). The diet was a controlled program of underfeeding during which meals were provided at individual calorie levels (approximately 400 kcal/d). Exercise (3 d/wk) involved treadmill walking at an intensity of 45-50% (moderate-intensity) or 70-75% (vigorous-intensity) of heart rate reserve. The primary outcome was abdominal visceral fat volume. RESULTS Average weight loss for the 95 women who completed the study was 12.1 kg (+/-4.5 kg) and was not significantly different across groups. Maximal oxygen uptake ( O(2)max) increased more in the CR + vigorous-intensity group than in either of the other groups (P < 0.05). The CR-only group lost relatively more lean mass than did either exercise group (P < 0.05). All groups showed similar decreases in abdominal visceral fat (approximately 25%; P < 0.001 for all). However, changes in visceral fat were inversely related to increases in O(2)max (P < 0.01). Changes in lipids, fasting glucose or insulin, and 2-h glucose and insulin areas during the oral-glucose-tolerance test were similar across treatment groups. CONCLUSION With a similar amount of total weight loss, lean mass is preserved, but there is not a preferential loss of abdominal fat when either moderate- or vigorous-intensity aerobic exercise is performed during caloric restriction. This trial was registered at (ClinicalTrials.gov) as: NCT00664729.

Does the Amount of Fat Mass Predict Age-Related Loss of Lean Mass, Muscle Strength, and Muscle Quality in Older Adults?

BACKGROUND An excessive amount of adipose tissue may contribute to sarcopenia and may be one mechanism underlying accelerated loss of muscle mass and strength with aging. We therefore examined the association of baseline total body fat with changes in leg lean mass, muscle strength, and muscle quality over 7 years of follow-up and whether this link was explained by adipocytokines and insulin resistance. METHODS Data were from 2,307 men and women, aged 70-79 years, participating in the Health, Aging, and Body Composition study. Total fat mass was acquired from dual energy X-ray absorptiometry. Leg lean mass was assessed by dual energy X-ray absorptiometry in Years 1, 2, 3, 4, 5, 6, and 8. Knee extension strength was measured by isokinetic dynamometer in Years 1, 2, 4, 6, and 8. Muscle quality was calculated as muscle strength divided by leg lean mass. RESULTS Every SD greater fat mass was related to 1.3 kg more leg lean mass at baseline in men and 1.5 kg in women (p < .01). Greater fat mass was also associated with a greater decline in leg lean mass in both men and women (0.02 kg/year, p < .01), which was not explained by higher levels of adipocytokines and insulin resistance. Larger fat mass was related to significantly greater muscle strength but significantly lower muscle quality at baseline (p < .01). No significant differences in decline of muscle strength and quality were found. CONCLUSIONS High fatness was associated with lower muscle quality, and it predicts accelerated loss of lean mass. Prevention of greater fatness in old age may decrease the loss of lean mass and maintain muscle quality and thereby reducing disability and mobility impairments.

Chronic Inflammation: Role of Adipose Tissue and Modulation by Weight Loss

Chronic inflammation has been linked with an increased risk of type 2 diabetes and cardiovascular disease. As an endocrine and inflammatory organ, adipose tissue is an important source of circulating pro-inflammatory cytokines. Current evidence strongly supports that chronic inflammation is associated with enlarged body fat mass. Moreover, inflammation is independently linked with abdominal, especially visceral fat mass, possibly due to the regional variation in adipose tissue cytokine production. In addition to pharmacological approaches, lifestyle modifications have been advocated for the treatment of chronic inflammation. A number of studies have indicated that either weight loss via energy restriction, or energy restriction plus other strategies (aerobic exercise, behavioral counseling, and liposuction), could reduce chronic inflammation. While the amount of weight loss tends to be important, exercise and other strategies may have additional effects. A few studies have reported weight loss effects on adipose tissue cytokine production. Weight loss reduces subcutaneous adipose tissue production of pro-inflammatory cytokines (i.e. interleukin 6, tumor necrosis factor alpha) and increases adipose expression of anti-inflammatory cytokines (i.e. interleukin 10, interleukin 1 receptor antagonist). More studies are needed to investigate the role of regional adipose tissue cytokine production in regulation of inflammation and the modulating effects of weight loss.

Weight Regain is Related to Decreases in Physical Activity During Weight Loss

PURPOSE To examine whether adaptations in physical activity energy expenditure (PAEE) and resting metabolic rate (RMR) during weight loss were associated with future weight regain in overweight/obese, older women. RESEARCH METHODS AND PROCEDURES Thirty-four overweight/obese (BMI = 25-40 kg x m(-2)), postmenopausal women underwent a 20-wk weight loss intervention of hypocaloric diet with (low- or high-intensity) or without treadmill walking (weekly caloric deficit was approximately 11,760 kJ), with a subsequent 12-month follow-up. RMR (via indirect calorimetry), PAEE (by RT3 accelerometer), and body composition (by dual-energy x-ray absorptiometry) were measured before and after intervention. Body weight and self-reported information on physical activity were collected after intervention and at 6 and 12 months after intervention. RESULTS The intervention resulted in decreases in body weight, lean mass, fat mass, percent body fat, RMR, and PAEE (P < 0.001 for all). Weight regain was 2.9 +/- 3.3 kg (-3.1 to +9.2 kg) at 6 months and 5.2 +/- 5.0 kg (-2.3 to +21.7 kg) at 12 months after intervention. The amount of weight regained after 6 and 12 months was inversely associated with decreases in PAEE during the weight loss intervention (r = -0.521, P = 0.002 and r = -0.404, P = 0.018, respectively), such that women with larger declines in PAEE during weight loss experienced greater weight regain during follow-up. Weight regain was not associated with changes in RMR during intervention or with self-reported physical activity during follow-up. CONCLUSION This study demonstrates that although both RMR and PAEE decreased during weight loss in postmenopausal women, maintaining high levels of daily physical activity during weight loss may be important to mitigate weight regain after weight loss.

Physical function improvements after laparoscopic Roux-en-Y gastric bypass surgery

BACKGROUND Obesity is a risk factor for impaired physical function and disability, with the degree of impairment most compromised in extreme obesity. Mild-to-moderate weight loss has been shown to improve function in older adults. The impact of laparoscopic Roux-en-Y gastric bypass surgery on weight loss and physical function in morbidly obese individuals was assessed. METHODS This longitudinal, observational study followed up 28 morbidly obese men and women (body mass index > or = 40.0 kg/m(2)) for 12 months after laparoscopic Roux-en-Y gastric bypass. Physical function (self-report using the Fitness Arthritis and Seniors Trial disability questionnaire; performance tasks using the Short Physical Performance Battery and a lateral mobility task); strength (maximal isometric knee torque); and body composition measured using bioelectrical impedance were determined before surgery (baseline) and at 3 weeks, 3 months, 6 months, and 12 months after surgery. RESULTS The 12-month weight loss was 34.2% (excess weight loss 59.8%), with a mean fat mass loss of 46 kg and a loss of fat free mass of 6.6 kg. The performance tasks and self-reported questionnaire scores had improved by 3 months after surgery compared with baseline, with selected measures showing less impairment and disability in as few as 3 weeks after surgery. Muscle quality, as measured using the maximal torque per kilogram body weight, was greater at 6 months than at baseline. CONCLUSION The results of our study have shown that in morbidly obese individuals with a high risk of mobility impairments, surgical procedures to reduce body weight increase mobility and improve performance of daily activities in as few as 3 weeks after gastric bypass surgery.

Resting energy expenditure changes with weight loss: racial differences

It is controversial whether weight loss reduces resting energy expenditure (REE) to a different magnitude in black and white women. This aim of this study was to determine whether changes in REE with weight loss were different between black and white postmenopausal women, and whether changes in body composition (including regional lean and fat mass) were associated with REE changes within each race. Black (n = 26) and white (n = 65) women (age = 58.2 ± 5.4 years, 25 < BMI < 40 kg/m2) completed a 20‐week weight‐loss intervention. Body weight, lean and fat mass (total body, limb, and trunk) via dual‐energy X‐ray absorptiometry, and REE via indirect calorimetry were measured before and after the intervention. We found that baseline REE positively correlated with body weight, lean and fat mass (total, limb, and trunk) in white women only (P < 0.05 for all). The intervention decreased absolute REE in both races similarly (1,279 ± 162 to 1,204 ± 169 kcal/day in blacks; 1,315 ± 200 to 1,209 ± 185 kcal/day in whites). REE remained decreased after adjusting for changes in total or limb lean mass in black (1,302–1,182 kcal/day, P = 0.043; 1,298–1,144 kcal/day, P = 0.006, respectively), but not in white, women. Changes in REE correlated with changes in body weight (partial r = 0.277) and fat mass (partial r = 0.295, 0.275, and 0.254 for total, limb, and trunk, respectively; P < 0.05) independent of baseline REE in white women. Therefore, with weight loss, REE decreased in proportion to the amount of fat and lean mass lost in white, but not black, women.

Physical activity and telomere length: Impact of aging and potential mechanisms of action

Telomeres protect the integrity of information-carrying DNA by serving as caps on the terminal portions of chromosomes. Telomere length decreases with aging, and this contributes to cell senescence. Recent evidence supports that telomere length of leukocytes and skeletal muscle cells may be positively associated with healthy living and inversely correlated with the risk of several age-related diseases, including cancer, cardiovascular disease, obesity, diabetes, chronic pain, and stress. In observational studies, higher levels of physical activity or exercise are related to longer telomere lengths in various populations, and athletes tend to have longer telomere lengths than non-athletes. This relationship is particularly evident in older individuals, suggesting a role of physical activity in combating the typical age-induced decrements in telomere length. To date, a small number of exercise interventions have been executed to examine the potential influence of chronic exercise on telomere length, but these studies have not fully established such relationship. Several potential mechanisms through which physical activity or exercise could affect telomere length are discussed, including changes in telomerase activity, oxidative stress, inflammation, and decreased skeletal muscle satellite cell content. Future research is needed to mechanistically examine the effects of various modalities of exercise on telomere length in middle-aged and older adults, as well as in specific clinical populations.

Addition of Exercise Increases Plasma Adiponectin and Release from Adipose Tissue.

INTRODUCTION Adiponectin is an adipose tissue-derived anti-inflammatory protein that is down-regulated in obesity. The effects of caloric restriction and exercise-induced weight loss on adiponectin are not clear. PURPOSE To determine whether addition of aerobic exercise training to caloric restriction has additive effects over caloric restriction alone on circulating adiponectin concentrations and adiponectin release from abdominal and gluteal adipose tissue. METHODS Overweight or obese (body mass index, 25-40 kg·m(-2); waist >88 cm) postmenopausal women were randomized to 20-wk caloric restriction with and without aerobic exercise (CR + EX, n = 48; and CR, n = 22). Blood samples were collected for measuring plasma adiponectin concentration, and abdominal and gluteal subcutaneous adipose tissue biopsies were performed in a subgroup to determine in vitro adiponectin release, before and after the interventions. RESULTS The interventions elicited similar amounts of weight loss (CR + EX, -11.3 ± 4.6 kg; CR,-11.2 ± 3.4 kg) and fat loss (CR + EX, -8.0 ± 3.5 kg; CR, -7.4 ± 2.7 kg). The two groups had differential changes in plasma adiponectin concentrations (for interaction, P = 0.014); CR + EX increased (6.9 ± 3.9 to 8.5 ± 4.9 μg·mL(-1); P = 0.0001), whereas CR did not alter (6.4 ± 4.4 to 6.5 ± 4.5 μg·mL(-1); P = 0.42) plasma adiponectin. Likewise, adiponectin release from abdominal and gluteal subcutaneous adipose tissue increased with CR + EX (P = 0.0076 and P = 0.089, respectively) but did not change with CR (P = 0.13 and P = 0.95, respectively). CONCLUSION Despite similar reductions in body weight and fat mass, the addition of aerobic exercise to caloric restriction increased plasma adiponectin concentrations, which may be partly explained by increased adiponectin release from abdominal and gluteal subcutaneous adipose tissue.

Aerobic exercise training attenuates obesity-related hypogonadism in male rats.

INTRODUCTION Hypogonadism is associated with obesity and other features of metabolic syndrome in males. PURPOSE The purpose of this study was to compare lean and obese male Zucker rats on their reproductive endocrine function in response to aerobic exercise training. METHODS Lean (Fa/Fa) and obese (fa/fa) male Zucker rats at 2 months of age were randomly assigned to a sedentary and an aerobic exercise training group (lean sedentary, n = 7; lean exercise, n = 8; obese sedentary, n = 7; obese exercise, n = 7). The exercise group walked on a rat treadmill, starting at 10 m · min(-1) for 20 min and building up to 20 m · min(-1) for 60 min, five times per week for 8 wk. Serum levels of total and free testosterone and testicular levels of testosterone, as well as epididymal and inguinal adipose tissue monocyte chemotactic protein 1 release levels, were measured. RESULTS There were significant obesity-by-exercise interactions on serum levels of total and free testosterone and testicular levels of testosterone (all P < 0.05). Compared to lean sedentary rats, obese sedentary rats had lower serum and testicular testosterone levels (0.72- to 0.74-fold, all P < 0.001). There were no group differences between lean sedentary and lean exercise rats on serum and testicular testosterone levels. However, compared to the obese sedentary group, the obese exercise group had higher serum and testicular testosterone levels (1.37- to 1.47-fold, all P < 0.05). In the whole cohort, serum and testicular testosterone levels were inversely related to epididymal adipose tissue monocyte chemotactic protein 1 secretion (r = -0.40 to r = -0.45, all P < 0.05). CONCLUSIONS Our results support that aerobic exercise training could improve severe obesity-related hypogonadism in male Zucker rats. The underlying mechanism needs to be further clarified.