FTO genotype and the weight loss benefits of moderate intensity exercise.
ABSTRACT: The fat mass and obesity-associated (FTO) gene was genotyped for the participants in the Dose-Response to Exercise in postmenopausal Women (DREW) trial and analyses were performed to determine whether an FTO variant was associated with adiposity and cardiorespiratory fitness (CRF) before and after 6 months of moderate intensity exercise in white women (n = 234). The A/A homozygotes for rs8050136 had a higher BMI (kg/m(2)) compared to C/C homozygotes at baseline (32.8 (0.6) vs. 31.0 (0.4), respectively; P < 0.05) and at follow-up (31.9 (0.6) vs. 30.4 (0.5), respectively; P < 0.05). Weight loss occurred after exercise, but there was no significant genotype by exercise interaction over time. Exploratory analyses among women exposed to moderate intensity exercise meeting, or exceeding, the physical activity recommendation found that those homozygous A/A lost significantly more weight than the C allele carriers (-3.3 (0.7) kg vs. -1.4 (0.4) kg and -1.5 (0.5) kg, respectively; P < 0.05). CRF, defined as VO(2peak) (oxygen consumption), increased after exercise and the magnitude of the increase was similar for each genotype. In conclusion, women genetically predisposed to being obese experienced weight loss and CRF benefits with moderate intensity exercise, with additional weight loss observed when the women met or exceeded the physical activity recommendations.
Project description:Exercise intensity may affect the selective loss of abdominal adipose tissue.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.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.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.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.
Project description:Background:Physical exercise and activity status may modify the effect of the fat mass- and obesity-associated (FTO) genotype on body weight and obesity risk. To understand the interaction between FTO's effect and physical activity, the present study investigated the effects of high and low intensity exercise on FTO mRNA and protein expression, and potential modifiers of exercise-induced changes in FTO in healthy-weighted individuals. Methods:Twenty-eight untrained males and females (25.4?±?1.1?years; 73.1?±?2.0?kg; 178.8?±?1.4?cm; 39.0?±?1.2?ml.kg.min-?1 VO2peak) were genotyped for the FTO rs9939609 (T?>?A) polymorphism and performed isocaloric (400?kcal) cycle ergometer exercise on two separate occasions at different intensities: 80% (High Intensity (HI)) and 40% (Low Intensity (LO)) VO2peak. Skeletal muscle biopsies (vastus lateralis) and blood samples were taken pre-exercise and following 10 and 90 mins passive recovery. Results:FTO mRNA expression was significantly decreased after HI intensity exercise (p?=?0.003). No differences in basal and post-exercise FTO protein expression were evident between FTO genotypes. Phosphorylated adenosine monophosphate-activated protein kinase (AMPK) and Akt substrate of 160?kDa (AS160) were significantly increased following HI intensity exercise (p?<?0.05). Multivariate models of metabolomic data (orthogonal two partial least squares discriminant analysis (O2PLS-DA)) were unable to detect any significant metabolic differences between genotypes with either exercise trial (p?>?0.05). However, skeletal muscle glucose accumulation at 10 mins following HI (p?=?0.021) and LO (p?=?0.033) intensity exercise was greater in AA genotypes compared to TT genotypes. Conclusion:Our novel data provides preliminary evidence regarding the effects of exercise on FTO expression in skeletal muscle. Specifically, high intensity exercise downregulates expression of FTO mRNA and suggests that in addition to nutritional regulation, FTO could also be regulated by exercise. Trial registration:ACTRN12612001230842. Registered 21 November 2012 - Prospectively registered, https://www.anzctr.org.au/.
Project description:While performing aerobic exercise during chemotherapy has been proven feasible and safe, the efficacy of aerobic training on cardiorespiratory fitness (CRF) in women with breast cancer undergoing chemotherapy has not yet been systematically assessed. Therefore, the objective of this work was to determine (a) the efficacy of aerobic training to improve CRF; (b) the role of aerobic training intensity (moderate or vigorous) on CRF response; (c) the effect of the aerobic training mode (continuous or interval) on changes in CRF in women with breast cancer (BC) receiving chemotherapy. A systematic review and meta-analysis were conducted as per PRISMA guidelines, and randomized controlled trials comparing usual care (UC) and aerobic training in women with BC undergoing chemotherapy were eligible. The results suggest that increases in CRF are favored by (a) aerobic training when compared to usual care; (b) vigorous-intensity aerobic exercise (64-90% of maximal oxygen uptake, VO2max) when compared to moderate-intensity aerobic exercise (46-63% of VO2max); and (c) both continuous and interval aerobic training are effective at increasing the VO2max. Aerobic training improves CRF in women with BC undergoing chemotherapy. Notably, training intensity significantly impacts the VO2max response. Where appropriate, vigorous intensity aerobic training should be considered for women with BC receiving chemotherapy.
Project description:Objective/Background: Exercise training has been demonstrated to beneficially influence mean-level measures of sleep; however, few studies have examined the impact of an exercise intervention on night-to-night variability in sleep. This study investigated whether four months of moderate-intensity exercise impacted night-to-night variability in sleep among older women. Methods: Participants (n = 49) were randomized to one of two moderate-intensity walking programs with different doses of energy expenditure: low-dose (n = 23: 8 kcal/kg of body weight per week) or high-dose (n = 26: 14 kcal/kg of body weight per week). Sleep parameters were assessed objectively via actigraphy at baseline, mid- (2 months), and postintervention (4 months). Nightly variability in each of the sleep parameters was calculated using the seven-day standard deviation (SD) and a coefficient of variation (SD/mean x 100%). Cardiorespiratory fitness (VO2peak) was measured at baseline and postintervention using a graded treadmill test. Results: Both measures of nightly variability demonstrated a borderline to significantly lower amount of night-to-night variability in wake time after sleep onset (WASO) and number of awakenings at postintervention in comparison to baseline (p ? 0.05). Higher VO2peak levels at baseline were associated with less time in bed and lower total sleep time variability throughout the exercise intervention (p < 0.05). Conclusion: Overall, participation in moderate-intensity exercise was observed to reduce the amount of nightly variability for WASO and number of awakenings over time in older women.
Project description:PURPOSE:This trial aimed to demonstrate the feasibility of high-intensity interval training (HIIT) in postmenopausal, overweight/obese women at high risk of invasive breast cancer and to explore HIIT on changes in cardiorespiratory fitness (CRF), body weight, and body mass index (BMI) compared with moderate-intensity continuous training (MICT) and usual care (UC). METHODS:Forty-four women were randomized to HIIT, MICT, or UC for a 12-wk, thrice weekly, supervised exercise intervention. HIIT included a 5-min warm-up at 50%-70% HRpeak, four cycles of 4 min at 90%-100% HRpeak, followed by 3 min at 50%-70% HRpeak. MICT consisted of 41 min at 60%-70% HRpeak. Feasibility was assessed by consent, adherence, compliance, and retention rates. CRF, body weight, and BMI were measured at baseline and end of study. Repeated-measures linear mixed models were used to assess within- and between-group differences. RESULTS:Average age was 63.9 ± 8.8 yr. BMI was 30.9 ± 5.7 kg·m. Participants completed 90% and 89% of HIIT and MICT workouts, respectively, with 100% compliance to the exercise prescriptions. No serious adverse events were reported. Compared with MICT and UC, HIIT exhibited improvements in change in treadmill time (101 s greater than MICT, and 125 s greater than UC, respectively, P < 0.001). Compared with UC, HIIT exhibited improvement in changes in absolute and relative V?O2peak (a 0.15-L·min increase, P = 0.005, and a 2.3-mL·kg?min increase, P = 0.004). There were no significant differences between groups for body weight or BMI (P > 0.05). CONCLUSIONS:HIIT is feasible, safe, and seems to promote greater improvements in CRF compared with MICT and UC in women at high risk for breast cancer.
Project description:Cancer related fatigue (CRF) is a common and debilitating side-effect of radiotherapy in breast cancer patients. Physical activity interventions can attenuate CRF but evidence in African-American women with breast cancer is lacking.The "Pedlar" Study is a prospective, 8-week structured moderate-intensity exercise intervention, delivered concurrently with radiotherapy, to reduce CRF and improve health-related quality of life among African American breast cancer patients. Forty African American women with breast cancer scheduled to receive radiation therapy at MedStar Washington Hospital Center will be randomized to one of the two trial arms: 1) a facility-based aerobic exercise utilizing a portable stationary pedal exerciser; and 2) a control group. Intervention arm participants will exercise at the hospital either before or after their radiation treatment. Assessments will be conducted at baseline, 4, and 8 weeks. The outcome variables are CRF, biomarkers of inflammation, and health-related quality of life.The Pedlar Study will provide preliminary evidence on whether a short-term moderate-intensity exercise intervention might be effective in reducing CRF in African American women undergoing radiotherapy for breast cancer, and whether this effect is mediated by inflammation.
Project description:OBJECTIVE:This study aimed to evaluate the impact of timing of exercise initiation on weight loss within a behavioral weight loss program. METHODS:Adults with overweight or obesity (N?=?170; age 18-55 years; BMI 25-42 kg/m2 ; 83.5% women) were enrolled in an 18-month behavioral weight loss program consisting of a reduced-calorie diet, exercise, and group-based support. The standard group (STD) received a supervised exercise program (progressing to 300 min/wk of moderate-intensity aerobic exercise) during months 0 to 6. The sequential group (SEQ) was asked to refrain from changing exercise during months 0 to 6 and received the supervised exercise program during months 7 to 12. On completion of supervised exercise, both groups were instructed to continue 300 min/wk of moderate-intensity exercise for the study duration. RESULTS:At 6 months, the STD group exhibited greater reductions in body weight (-8.7?±?0.7 kg) compared with the SEQ group (-6.9?±?0.6 kg; P?=?0.047). Between 6 and 18 months, the STD group regained more weight (2.5?±?0.8 kg vs. 0.0?±?0.8 kg; P?=?0.02). At 18 months, there were no between-group differences in changes in weight (STD: -6.9?±?1.2 kg; SEQ: -7.9?±?1.2 kg), fat mass, lean mass, physical activity, or attrition. CONCLUSIONS:Both immediate and delayed exercise initiation within a behavioral weight loss program resulted in clinically meaningful weight loss at 18 months. Thus, timing of exercise initiation can be personalized based on patient preference.
Project description:FTO gene single nucleotide polymorphisms (SNPs) have been shown to be associated with obesity-related traits and type 2 diabetes. Several small studies have suggested a greater than expected effect of the FTO rs9939609 SNP on weight in polycystic ovary syndrome (PCOS). We therefore aimed to examine the impact of FTO genotype on BMI and weight in PCOS.A systematic search of medical databases (PubMed, EMBASE and Cochrane CENTRAL) was conducted up to the end of April 2011. Seven studies describing eight distinct PCOS cohorts were retrieved; seven were genotyped for SNP rs9939609 and one for SNP rs1421085. The per allele effect on BMI and body weight increase was calculated and subjected to meta-analysis.A total of 2,548 women with PCOS were included in the study; 762 were TT homozygotes, 1,253 had an AT/CT genotype, and 533 were AA/CC homozygotes. Each additional copy of the effect allele (A/C) increased the BMI by a mean of 0.19 z score units (95% CI 0.13, 0.24; p = 2.26 × 10(-11)) and body weight by a mean of 0.20 z score units (95% CI 0.14, 0.26; p = 1.02 × 10(-10)). This translated into an approximately 3.3 kg/m(2) increase in BMI and an approximately 9.6 kg gain in body weight between TT and AA/CC homozygotes. The association between FTO genotypes and BMI was stronger in the cohorts with PCOS than in the general female populations from large genome-wide association studies. Deviation from an additive genetic model was observed in heavier populations.The effect of FTO SNPs on obesity-related traits in PCOS seems to be more than two times greater than the effect found in large population-based studies. This suggests an interaction between FTO and the metabolic context or polygenic background of PCOS.
Project description:The fat mass (FM) and obesity-associated (FTO) gene is the first obesity-susceptibility gene identified by genome-wide association scans and confirmed in several follow-up studies. Homozygotes for the risk allele (A/A) have 1.67 times greater risk of obesity than those who do not have the allele. However, it is not known whether regular exercise-induced changes in body composition are influenced by the FTO genotype. The purpose of our study was to test whether the FTO genotype is associated with exercise-induced changes in adiposity. Body composition was derived from underwater weighing before and after a 20-week endurance training program in 481 previously sedentary white subjects of the HERITAGE Family Study. FTO single-nucleotide polymorphism (SNP) rs8050136 was genotyped using Illumina GoldenGate assay. In the sedentary state, the A/A homozygotes were significantly heavier and fatter than the heterozygotes and the C/C homozygotes in men (P = 0.004) but not in women (P = 0.331; gene-by-sex interaction P = 0.0053). The FTO genotype was associated with body fat responses to regular exercise (P < 0.005; adjusted for age, sex, and baseline value of response trait): carriers of the C allele showed three times greater FM and %body fat losses than the A/A homozygotes. The FTO genotype explained 2% of the variance in adiposity changes. Our data suggest that the FTO obesity-susceptibility genotype influences the body fat responses to regular exercise. Resistance to exercise-induced reduction in total adiposity may represent one mechanism by which the FTO A allele promotes overweight and obesity.
Project description:Background: High Intensity Interval Training (HIIT) is a sustainable and effective method for improving Cardiorespiratory Fitness (CRF) in adolescents. HIIT is proven to produce equal or greater improvements in CRF when compared to moderate intensity continuous exercise (MICE) in adolescents. Methods: The studies included were considered eligible if: (1) Participants were adolescents (11-18 years old); (2) Examined changes in CRF measured either directly or indirectly; (3) Included a non-exercising control group or MICE comparison group; (4) Participants were matched at enrolment; (5) Reported HIIT protocol information; (6) Provided HIIT intensity. A meta-analysis was conducted to determine the effect of HIIT on CRF. Meta-regression and moderator analyses were performed out to quantitatively examine moderators of protocol design on CRF improvements. Results: HIIT displays a moderate effect to improve CRF (g = 0.86, 95% CI 0.518-1.106, p < 0.001). Neither study duration (weeks), nor total or weekly accumulated HIIT volume (min) displayed any significant moderation effect on pooled improvement on CRF (p > 0.05). Conclusions: HIIT is an effective method to improve CRF in adolescents, irrespective of body composition. Notably, meta regression analysis identified that prolonged high volume HIIT programs are similarly effective to short term low volume HIIT programs. This becomes of particular interest for those involved in school curricula, where short HIIT exercise may provide a pragmatic adjunct to the health benefits of Physical Education (PE) lessons.