Relationships between exercise-induced reductions in thigh intermuscular adipose tissue, changes in lipoprotein particle size, and visceral adiposity

Small LDL and HDL particle size are characteristic of a proatherogenic lipoprotein profile. Aerobic exercise increases these particle sizes. Although visceral adipose tissue (VAT) has been strongly linked with dyslipidemia, the importance of intermuscular adipose tissue (IMAT) to dyslipidemia and exercise responses is less well understood. We measured exercise-associated changes in thigh IMAT and VAT and examined their relationships with changes in LDL and HDL particle size. Sedentary, dyslipidemic, overweight subjects (n = 73) completed 8-9 mo of aerobic training. Linear regression models were used to compare the power of IMAT change and VAT change to predict lipoprotein size changes. In men alone (n = 40), IMAT change correlated inversely with both HDL size change (r = -0.42, P = 0.007) and LDL size change (r = -0.52, P < 0.001). That is, reduction of IMAT was associated with a shift toward larger, less atherogenic lipoprotein particles. No significant correlations were observed in women. After adding VAT change to the model, IMAT change was the only significant predictor of either HDL size change (P = 0.034 for IMAT vs. 0.162 for VAT) or LDL size change (P = 0.004 for IMAT vs. 0.189 for VAT) in men. In conclusion, in overweight dyslipidemic men, exercise-associated change in thigh IMAT was inversely correlated with both HDL and LDL size change and was more predictive of these lipoprotein changes than was change in VAT. Reducing IMAT through aerobic exercise may be functionally related to some improvements in atherogenic dyslipidemia in men.     

Femoral-gluteal subcutaneous and intermuscular adipose tissues have independent and opposing relationships with CVD risk.

Femoral-gluteal adipose tissue (AT) may be cardioprotective through fatty acids uptake. Femoral-gluteal AT has previously been defined as leg fat measured by dual energy x-ray absorptiometry (DXA); however, subcutaneous adipose tissue (SAT) and intermuscular adipose tissue (IMAT) are inseparable using DXA. This study investigated the independent relationships between femoral-gluteal SAT, femoral-gluteal IMAT, and cardiovascular disease (CVD) risk factors [fasting serum measures of glucose, total cholesterol (TC), high density lipoprotein cholesterol (HDLC), triglycerides (TG) and insulin] and whether race differences exist in femoral-gluteal AT distribution. Adult Caucasians (56 men and 104 women), African-Americans (37 men and 76 women), and Asians (11 men and 35 women) had total AT (TAT) including femoral-gluteal AT (upper leg SAT and IMAT) and visceral AT (VAT) by magnetic resonance imaging (MRI). General linear models identified the independent effects of femoral-gluteal SAT and femoral-gluteal IMAT on each risk factor after covarying for TAT, VAT, age, race, sex, and two-way interactions. Femoral-gluteal IMAT and glucose (P < 0.05) were positively associated independent of VAT. There were also significant inverse associations between femoral-gluteal SAT and insulin (P < 0.01) and TG (P < 0.05), although the addition of VAT rendered these effects nonsignificant, possibly due to collinearity. Asian women had less femoral-gluteal SAT and greater VAT than Caucasians and African-Americans (P < 0.05) and Asian and African-American men had greater femoral-gluteal IMAT than Caucasians, adjusted for age and TAT (P < 0.05 for both). Femoral-gluteal SAT and femoral-gluteal IMAT distribution varies by sex and race, and these two components have independent and opposing relationships with CVD risk factors.     

Plasma leptin in moderately obese men: independent effects of weight loss and aerobic exercise

The independent effects of weight loss and exercise on plasma leptin and total (AT), subcutaneous (SAT), and visceral (VAT) adipose tissue were investigated in 52 obese men. Subjects were randomly assigned to four 12-wk protocols: 1) control (C, n = 8), 2) diet-induced weight loss (DWL, n = 14), 3) exercise-induced weight loss (EWL, n = 14), and 4) exercise with weight maintenance (EWS, n = 16). Plasma leptin was unchanged in C (from 7.8 +/- 1.3 to 7.7 +/- 1.0 ng/ml). Equivalent weight loss (7.5 kg) decreased leptin significantly but similarly (DWL, from 8.5 +/- 1.0 to 4.8 +/- 0.6 ng/ml; EWL, from 10.1 +/- 1.0 to 5.0 +/- 0.6 ng/ml). Exercise in the absence of weight loss did not alter leptin levels (from 10.1 +/- 1. 3 to 9.2 +/- 1.2 ng/ml). Changes in leptin correlated with changes in AT and SAT (both P < 0.05) but not in VAT. We conclude that reduction in adipose tissue after weight loss results in a collateral decrease in circulating leptin, and exercise, independent of its effects on weight loss, has no profound influence on leptin secretion.     

Lower extremity muscle size and strength and aerobic capacity decrease with caloric restriction but not with exercise-induced weight loss.

Caloric restriction (CR) results in fat loss; however, it may also result in loss of muscle and thereby reduce strength and aerobic capacity (VO2 max). These effects may not occur with exercise-induced weight loss (EX) because of the anabolic effects of exercise on heart and skeletal muscle. We tested the hypothesis that CR reduces muscle size and strength and VO2 max, whereas EX preserves or improves these parameters. Healthy 50- to 60-yr-old men and women (body mass index of 23.5-29.9 kg/m2) were studied before and after 12 mo of weight loss by CR (n = 18) or EX (n = 16). Lean mass was assessed by dual-energy X-ray absorptiometry, thigh muscle volume by MRI, isometric and isokinetic knee flexor strength by dynamometry, and treadmill VO2 max by indirect calorimetry. Both interventions caused significant decreases in body weight (CR: -10.7 +/- 1.4%, EX: -9.5 +/- 1.5%) and lean mass (CR: -3.5 +/- 0.7%, EX: -2.2 +/- 0.8%), with no significant differences between groups. Significant decreases in thigh muscle volume (-6.9 +/- 0.8%) and composite knee flexion strength (-7.2 +/- 3%) occurred in the CR group only. Absolute VO2 max decreased significantly in the CR group (-6.8 +/- 2.3%), whereas the EX group had significant increases in both absolute (+15.5 +/- 2.4%) and relative (+28.3 +/- 3.0%) VO2 max. These data provide evidence that muscle mass and absolute physical work capacity decrease in response to 12 mo of CR but not in response to a similar weight loss induced by exercise. These findings suggest that, during EX, the body adapts to maintain or even enhance physical performance capacity.     

Intermuscular Adipose Tissue and Metabolic Associations in HIV Infection

Intermuscular adipose tissue (IMAT) is associated with metabolic abnormalities similar to those associated with visceral adipose tissue (VAT). Increased IMAT has been found in obese human immunodeficiency virus (HIV)‐infected women. We hypothesized that IMAT, like VAT, would be similar or increased in HIV‐infected persons compared with healthy controls, despite decreases in subcutaneous adipose tissue (SAT) found in HIV infection. In the second FRAM (Study of Fat Redistribution and Metabolic Change in HIV infection) exam, we studied 425 HIV‐infected subjects and 211 controls (from the Coronary Artery Risk Development in Young Adults study) who had regional AT and skeletal muscle (SM) measured by magnetic resonance imaging (MRI). Multivariable linear regression identified factors associated with IMAT and its association with metabolites. Total IMAT was 51% lower in HIV‐infected participants compared with controls (P = 0.003). The HIV effect was attenuated after multivariable adjustment (to ?28%, P < 0.0001 in men and ?3.6%, P = 0.70 in women). Higher quantities of leg SAT, upper‐trunk SAT, and VAT were associated with higher IMAT in HIV‐infected participants, with weaker associations in controls. Stavudine use was associated with lower IMAT and SAT, but showed little relationship with VAT. In multivariable analyses, regional IMAT was associated with insulin resistance and triglycerides (TGs). Contrary to expectation, IMAT is not increased in HIV infection; after controlling for demographics, lifestyle, VAT, SAT, and SM, HIV⁺ men have lower IMAT compared with controls, whereas values for women are similar. Stavudine exposure is associated with both decreased IMAT and SAT, suggesting that IMAT shares cellular origins with SAT.     

The role of time of food intake on upcoming liver disease in male Wistar rat

Interventions against obesity, are mainly around changing calorie intake and energy expenditure. Recently, some studies focused on the influence of circadian time of food intake on metabolic status. Here, we compare the role of calorie restriction and time restricted feeding followed by high-fat diet started post weaning, First, 52 male Wistarrats (3 weeks old) were divided into two groups: the high-fat diet (HFD, n = 42) and the control group (CON1, n = 11). After 17 weeks, five rats were randomly selected from each group for sample preparation. In the second phase, the animals in HFD group were assigned into four groups (n = 9): (1) 30% calorie restriction (CR), (2) day intermittent fasting (DIF), (3) night intermittent fasting (NIF), (4) adlibitum food intake (AL), (5) remained animal from the first phase control (CON2). Seventeen weeks of HFD started post-weaning did not cause fatty liver but it caused a significant difference in the body and the adipose tissue weight (P0.05). The results showed that longtime HFD did not lead to liver steatosis while the incorrect time of food intake predisposes the animal to the upcoming liver disease. This data indicate a significant role of timing of food intake rather than nutrition composition itself.     

Impact of intra- and extra-osseous soft tissue composition on changes in bone mineral density with weight loss and regain

Recent studies report a significant gain in bone mineral density (BMD) after diet-induced weight loss. This might be explained by a measurement artefact. We therefore investigated the impact of intra- and extra-osseous soft tissue composition on bone measurements by dual X-ray absorptiometry (DXA) in a longitudinal study of diet-induced weight loss and regain in 55 women and 17 men (19-46 years, BMI 28.2-46.8 kg/m(2)). Total and regional BMD were measured before and after 12.7 ± 2.2 week diet-induced weight loss and 6 months after significant weight regain (≥30%). Hydration of fat free mass (FFM) was assessed by a 3-compartment model. Skeletal muscle (SM) mass, extra-osseous adipose tissue, and bone marrow were measured by whole body magnetic resonance imaging (MRI). Mean weight loss was -9.2 ± 4.4 kg (P < 0.001) and was followed by weight regain in a subgroup of 24 subjects (+6.3 ± 2.9 kg; P < 0.001). With weight loss, bone marrow and extra-osseous adipose tissue decreased whereas BMD increased at the total body, lumbar spine, and the legs (women only) but decreased at the pelvis (men only, all P < 0.05). The decrease in BMD(pelvis) correlated with the loss in visceral adipose tissue (VAT) (P < 0.05). Increases in BMD(legs) were reversed after weight regain and inversely correlated with BMD(legs) decreases. No other associations between changes in BMD and intra- or extra-osseous soft tissue composition were found. In conclusion, changes in extra-osseous soft tissue composition had a minor contribution to changes in BMD with weight loss and decreases in bone marrow adipose tissue (BMAT) were not related to changes in BMD.     

Intramyocellular lipid content and insulin sensitivity are increased following a short-term low-glycemic index diet and exercise intervention

The relationship between intramyocellular (IMCL) and extramyocellular lipid (EMCL) accumulation and skeletal muscle insulin resistance is complex and dynamic. We examined the effect of a short-term (7-day) low-glycemic index (LGI) diet and aerobic exercise training intervention (EX) on IMCL and insulin sensitivity in older, insulin-resistant humans. Participants (66 ± 1 yr, BMI 33 ± 1 kg/m(2)) were randomly assigned to a parallel, controlled feeding trial [either an LGI (LGI/EX, n = 7) or high GI (HGI/EX, n = 8) eucaloric diet] combined with supervised exercise (60 min/day, 85% HR(max)). Insulin sensitivity was determined via 40 mU·m(-2)·min(-1) hyperinsulinemic euglycemic clamp and soleus IMCL and EMCL content was assessed by (1)H-MR spectroscopy with correction for fiber orientation. BMI decreased (kg/m(2) -0.6 ± 0.2, LGI/EX; -0.7 ± 0.2, HGI/EX P < 0.0004) after both interventions with no interaction effect of diet composition. Clamp-derived insulin sensitivity increased by 0.91 ± 0.21 (LGI/EX) and 0.17 ± 0.55 mg·kg(-1)·min(-1) (HGI/EX), P = 0.04 (effect of time). HOMA-IR was reduced by -1.1 ± 0.4 (LGI/EX) and -0.1 ± 0.2 (HGI/EX), P = 0.007 (effect of time), P = 0.02 (time × trial). Although both interventions increased IMCL content, (Δ: 2.3 ± 1.3, LGI/EX; 1.4 ± 0.9, HGI/EX, P = 0.03), diet composition did not significantly effect the increase. However, the LGI/EX group showed a robust increase in the [IMCL]/[EMCL] ratio compared with the HGI/EX group (Δ: 0.5 ± 0.2 LGI/EX vs. 0.07 ± 0.1, P = 0.03). The LGI/EX group also demonstrated greater reductions in [EMCL] than the HGI/EX group (Δ: -5.8 ± 3.4, LGI/EX; 2.3 ± 1.1, HGI/EX, P = 0.03). Changes in muscle lipids and insulin sensitivity were not correlated; however, the change in [IMCL]/[EMCL] was negatively associated with the change in FPI (r = -0.78, P = 0.002) and HOMA-IR (r = -0.61, P = 0.03). These data suggest that increases in the IMCL pool following a low glycemic diet and exercise intervention may represent lipid repartitioning from EMCL. The lower systemic glucose levels that prevail while eating a low glycemic diet may promote redistribution of lipid stores in the muscle.     

Calorie restriction or exercise: effects on coronary heart disease risk factors. A randomized, controlled trial

Coronary heart disease (CHD) risk factors and the risk of CHD increase with increased adiposity. Fat loss induced by negative energy balance improves all metabolic CHD risk factors. To determine whether fat loss induced by long-term calorie restriction (CR) or increased energy expenditure induced by exercise (EX) has different effects on CHD risk factors in nonobese subjects, we conducted a 1-yr controlled trial involving 48 nonobese subjects who were randomly assigned to one of three groups: CR, 20% CR diet (n = 18); EX, 20% increase in energy expenditure through daily exercise with no increase in energy intake (n = 18); or HL, healthy lifestyle guidelines (n = 10). Subjects were 29 women and 17 men aged 57 +/- 3 yr, with BMI 27.3 +/- 2.0 kg/m(2). Assessments included total body fat by DEXA, lipoproteins, blood pressure, HOMA-IR, C-reactive protein (CRP), and estimated 10-yr CHD risk score. Body fat decreased by 6.3 +/- 3.8 kg in CR, 5.6 +/- 4.4 kg in EX, and 0.4 +/- 1.7 kg in HL, which corresponded to reductions of 24.9, 22.3, and 1.2% of baseline body fat mass, respectively. These CR- and EX-induced energy deficits were accompanied by reductions in most of the major CHD risk factors, including plasma LDL-cholesterol, total cholesterol/HDL ratio, HOMA-IR index, and CRP concentrations that were similar in the two intervention groups. Data from the present study provide evidence that CR- and EX-induced negative energy balance result in substantial and similar improvements in the major risk factors for CHD in normal-weight and overweight middle-aged adults.     

Exercise with calorie restriction improves insulin sensitivity and glycogen synthase activity in obese postmenopausal women with impaired glucose tolerance

Our objective was to compare the effects of in vivo insulin on skeletal muscle glycogen synthase (GS) activity in normal (NGT) vs. impaired glucose-tolerant (IGT) obese postmenopausal women and to determine whether an increase in insulin activation of GS is associated with an improvement in insulin sensitivity (M) following calorie restriction (CR) and/or aerobic exercise plus calorie restriction (AEX + CR) in women with NGT and IGT. We did a longitudinal, clinical intervention study of CR compared with AEX + CR. Overweight and obese women, 49-76 yr old, completed 6 mo of CR (n = 46) or AEX + CR (n = 50) with Vo(2?max), body composition, and glucose tolerance testing. Hyperinsulinemic euglycemic (80 mU·m(-2)·min(-1)) clamps (n = 73) and skeletal muscle biopsies (before and during clamp) (n = 58) were performed before and after the interventions (n = 50). After 120 min of hyperinsulinemia during the clamp, GS fractional activity and insulin's effect to increase GS fractional activity (insulin - basal) were significantly lower in IGT vs. NGT (P < 0.01) at baseline. GS total activity increased during the clamp in NGT (P < 0.05), but not IGT, at baseline. CR and AEX + CR resulted in a significant 8% weight loss with reductions in total fat mass, visceral fat, subcutaneous fat, and intramuscular fat. Overall, M increased (P < 0.01), and the change in M (postintervention - preintervention) was associated with the change in insulin-stimulated GS fractional activity (partial r = 0.44, P < 0.005). In IGT, the change (postintervention - preintervention) in insulin-stimulated GS total activity was greater following AEX + CR than CR alone (P < 0.05). In IGT, insulin-stimulated GS-independent (P < 0.005) and fractional activity (P = 0.06) increased following AEX + CR. We conclude that the greatest benefits at the whole body and cellular level (insulin activation of GS) in older women at highest risk for diabetes are derived from a lifestyle intervention that includes exercise and diet.     

Reduced bone mineral density is not associated with significantly reduced bone quality in men and women practicing long-term calorie restriction with adequate nutrition

Calorie restriction (CR) reduces bone quantity but not bone quality in rodents. Nothing is known regarding the long-term effects of CR with adequate intake of vitamin and minerals on bone quantity and quality in middle-aged lean individuals. In this study, we evaluated body composition, bone mineral density (BMD), and serum markers of bone turnover and inflammation in 32 volunteers who had been eating a CR diet (approximately 35% less calories than controls) for an average of 6.8 ± 5.2 years (mean age 52.7 ± 10.3 years) and 32 age- and sex-matched sedentary controls eating Western diets (WD). In a subgroup of 10 CR and 10 WD volunteers, we also measured trabecular bone (TB) microarchitecture of the distal radius using high-resolution magnetic resonance imaging. We found that the CR volunteers had significantly lower body mass index than the WD volunteers (18.9 ± 1.2 vs. 26.5 ± 2.2 kg m(-2) ; P = 0.0001). BMD of the lumbar spine (0.870 ± 0.11 vs. 1.138 ± 0.12 g cm(-2) , P = 0.0001) and hip (0.806 ± 0.12 vs. 1.047 ± 0.12 g cm(-2) , P = 0.0001) was also lower in the CR than in the WD group. Serum C-terminal telopeptide and bone-specific alkaline phosphatase concentration were similar between groups, while serum C-reactive protein (0.19 ± 0.26 vs. 1.46 ± 1.56 mg L(-1) , P = 0.0001) was lower in the CR group. Trabecular bone microarchitecture parameters such as the erosion index (0.916 ± 0.087 vs. 0.877 ± 0.088; P = 0.739) and surface-to-curve ratio (10.3 ± 1.4 vs. 12.1 ± 2.1, P = 0.440) were not significantly different between groups. These findings suggest that markedly reduced BMD is not associated with significantly reduced bone quality in middle-aged men and women practicing long-term calorie restriction with adequate nutrition.     

WISE 2005: responses of women to sublingual nitroglycerin before and after 56 days of 6° head-down bed rest

This study tested the hypothesis that cardiovascular effects of sublingual nitroglycerin (NG) would be exaggerated after 56 days of 6° head-down bed rest (HDBR) in women, and that an aerobic and resistive exercise countermeasure (EX, n = 8) would reduce the effect compared with HDBR without exercise (CON, n = 7). Middle cerebral artery maximal blood flow velocity (CBFV), cardiac stroke volume (SV), and superficial femoral artery blood flow (Doppler ultrasound) were recorded at baseline rest and for 5 min following 0.3 mg sublingual NG. Post-HDBR, NG caused greater increases in heart rate (HR) in CON compared with EX (+24.9 ± 7.7 and +18.8 ± 6.6 beats/min, respectively, P < 0.0001). The increase in HR combined with reductions in SV to maintain cardiac output. Systolic, mean, and pulse pressures were reduced 5-10 mmHg by NG, but total peripheral resistance was only slightly reduced at 3 min after NG. Reductions in CBFV of -12.5 ± 3.8 cm/s were seen after NG, but a reduction in the Doppler resistance index suggested dilation of the middle cerebral artery with no differences after HDBR. The femoral artery dilated with NG and blood flow was reduced ～50% with the appearance of large negative waves suggesting a marked increase in downstream resistance, but there were no effects of HDBR. In general, responses of women to NG were not altered by HDBR; the greater increase in HR in CON but not EX was probably a consequence of cardiovascular deconditioning. These results contrast with the hypothesis and a previous investigation of men after HDBR by revealing no change in cardiovascular responses to exogenous nitric oxide.     

Relationship between the Bertin index to estimate visceral adipose tissue from dual-energy X-ray absorptiometry and cardiometabolic risk factors before and after weight loss

The purpose of this study was to investigate the relationship between visceral adipose tissue (VAT), estimated with the Bertin index obtained from dual-energy X-ray absorptiometry (DXA), with cardiometabolic risk factors before and after a weight loss program and compare it with VAT measured with computed tomography (CT) scan. The study population for this analysis included 92 nondiabetic overweight and obese sedentary postmenopausal women (age: 58.1 ± 4.7 years, BMI: 31.8 ± 4.2 kg/m(2)) participating in a weight loss intervention that consisted of a caloric restricted diet with and without resistance training (RT). We measured (i) VAT using CT scan, (ii) body composition (using DXA) from which the Bertin index was calculated, (iii) cardiometabolic risk factors such as insulin sensitivity (using the hyperinsulinenic-euglycemic clamp technique), peak oxygen consumption, blood pressure, plasma lipids, C-reactive protein as well as fasting glucose and insulin. VAT levels for both methods significantly decreased after the weight loss intervention. Furthermore, no differences in VAT levels between both methods were observed before (88.0 ± 25.5 vs. 83.8 ± 22.0 cm(2)) and after (76.8 ± 27.8 vs. 73.6 ± 23.2 cm(2)) the weight loss intervention. In addition, the percent change in VAT levels after the weight loss intervention was similar between both methods (-13.0 ± 16.5 vs. -12.5 ± 12.6%). Moreover, similar relationships were observed between both measures of VAT with cardiometabolic risk factors before and after the weight loss intervention. Finally, results from the logistic regression analysis consistently showed that fat mass and lean body mass were independent predictors of pre- and post-VAT levels for both methods in our cohort. In conclusion, estimated visceral fat levels using the Bertin index may be able to trace variations of VAT after weight loss. This index also shows comparable relationships with cardiometabolic risk factors when compared to VAT measured using CT scan.     

The effect of caloric restriction interventions on growth hormone secretion in nonobese men and women

Lifespan in rodents is prolonged by caloric restriction (CR) and by mutations affecting the somatotropic axis. It is not known if CR can alter the age‐associated decline in growth hormone (GH), insulin‐like growth factor (IGF)‐1 and GH secretion. To evaluate the effect of CR on GH secretory dynamics; forty‐three young (36.8 ± 1.0 years), overweight (BMI 27.8 ± 0.7) men (n = 20) and women (n = 23) were randomized into four groups; control = 100% of energy requirements; CR = 25% caloric restriction; CR + EX = 12.5% CR + 12.5% increase in energy expenditure by structured exercise; LCD = low calorie diet until 15% weight reduction followed by weight maintenance. At baseline and after 6 months, body composition (DXA), abdominal visceral fat (CT) 11 h GH secretion (blood sampling every 10 min for 11 h; 21:00–08:00 hours) and deconvolution analysis were measured. After 6 months, weight (control: ?1 ± 1%, CR: ?10 ± 1%, CR + EX: ?10 ± 1%, LCD: ?14 ± 1%), fat mass (control: ?2 ± 3%, CR: ?24 ± 3%, CR + EX: ?25 ± 3%, LCD: ?31 ± 2%) and visceral fat (control: ?2 ± 4%, CR: ?28 ± 4%, CR + EX: ?27 ± 3%, LCD: ?36 ± 2%) were significantly (P < 0.001) reduced in the three intervention groups compared to control. Mean 11 h GH concentrations were not changed in CR or control but increased in CR + EX (P < 0.0001) and LCD (P < 0.0001) because of increased secretory burst mass (CR + EX: 34 ± 13%, LCD: 27 ± 22%, P < 0.05) and amplitude (CR + EX: 34 ± 14%, LCD: 30 ± 20%, P < 0.05) but not to changes in secretory burst frequency or GH half‐life. Fasting ghrelin was significantly increased from baseline in all three intervention groups; however, total IGF‐1 concentrations were increased only in CR + EX (10 ± 7%, P < 0.05) and LCD (19 ± 4%, P < 0.001). A 25% CR diet for 6 months does not change GH, GH secretion or IGF‐1 in nonobese men and women.     

Effect of calorie restriction on resting metabolic rate and spontaneous physical activity

Objective: It is unclear if resting metabolic rate (RMR) and spontaneous physical activity (SPA) decrease in weight‐reduced non‐obese participants. Additionally, it is unknown if changes in SPA, measured in a respiratory chamber, reflect changes in free‐living physical activity level (PAL). Research Methods and Procedures: Participants (N = 48) were randomized into 4 groups for 6 months: calorie restriction (CR, 25% restriction), CR plus structured exercise (CR+EX, 12.5% restriction plus 12.5% increased energy expenditure via exercise), low‐calorie diet (LCD, 890 kcal/d supplement diet until 15% weight loss, then weight maintenance), and control (weight maintenance). Measurements were collected at baseline, Month 3, and Month 6. Body composition and RMR were measured by DXA and indirect calorimetry, respectively. Two measures of SPA were collected in a respiratory chamber (percent of time active and kcal/d). Free‐living PAL (PAL = total daily energy expenditure by doubly labeled water/RMR) was also measured. Regression equations at baseline were used to adjust RMR for fat‐free mass and SPA (kcal/d) for body weight. Results: Adjusted RMR decreased at Month 3 in the CR group and at Month 6 in the CR+EX and LCD groups. Neither measure of SPA decreased significantly in any group. PAL decreased at Month 3 in the CR and LCD groups, but not in the CR+EX group, who engaged in structured exercise. Changes in SPA in the chamber and free‐living PAL were not related. Discussion: Body weight is defended in non‐obese participants during modest caloric restriction, evidenced by metabolic adaptation of RMR and reduced energy expenditure through physical activity.     

Breast Volume is an Independent Predictor of Visceral and Ectopic Fat in Premenopausal Women

It is suggested that a large breast size among women may predict type 2 diabetes risk independent of BMI and waist circumference (WC). The purpose of this study was to determine the independent associations of breast volume with cardiometabolic risk factors and regional fat distribution. A total of 92 overweight or obese premenopausal women (age = 39.9 ± 6.8 years) underwent full‐body magnetic resonance imaging (MRI) for the assessment of breast volume, visceral adipose tissue (VAT), abdominal and lower‐body subcutaneous AT (SAT), and intermuscular AT (IMAT), a 2‐h oral glucose tolerance test (OGTT), and fasting phlebotomy for assessment of triglyceride, total, high‐density lipoprotein–, and low‐density lipoprotein–cholesterol levels. Breast volume was not associated with any of the cardiometabolic risk factors assessed (P > 0.05). However, VAT was consistently associated with a number of cardiometabolic risk factors (OGTT glucose, OGTT insulin, and triglyceride levels) after controlling for age, BMI, WC, breast volume, and the other AT depots. In univariate models, breast volume was positively associated with VAT, IMAT, and abdominal and lower‐body SAT (P < 0.05). After controlling for age, BMI, and WC level, breast volume remained positively associated with VAT and IMAT (P < 0.05), such that women with the highest breast volume had ～1.1 and 1.3 kg more VAT and IMAT, respectively, but no more abdominal or lower‐body SAT, by comparison to women with the smallest breast volume. Thus, the previously documented association between breast size and type 2 diabetes risk may be in part explained by excess VAT and/or IMAT deposition.     

Effects of different weight loss protocols on serum leptin levels in obese females

We investigated the effects of different weight loss protocols on leptin levels in obese females with the aim of addressing the leptin resistance which has been found to be an aggravating factor in obesity. Twenty-four obese females enrolled to one of three 12-week weight loss protocols: orlistat-induced weight loss (OWL, n=8), exercise-induced weight loss (EWL, n=8) and orlistat plus exercise-induced weight loss (OEWL, n=8). Serum leptin levels were measured in duplicate by radioimmunoassay. There were significant reductions (P<0.01) in body weight and fat mass after the 12 week period in all groups: -11.4+/-0.5 kg and -9.8+/-0.5 kg (OEWL), -8.3+/-0.8 kg and -5.7+/-0.9 kg (OWL), -8.9+/-1.2 kg and -7.4+/-1.2 kg (EWL), respectively. Serum leptin levels were also decreased markedly in all groups: -59.2 % (OEWL1), -37.8 % (OWL) and -48.6 % (EWL) (P<0.01 all). In addition, there were marked decreases in leptin levels for each kilogram of fat mass after the 12 week period: -48.2+/-7.2 % (OEWL), -27.8+/-4.8 % (OWL) and -39.3+/-4.3 % (EWL) (P<0.01 all). Decreases in serum leptin levels expressed per kilogram of fat mass were significantly higher in the OEWL group compared to the OWL group (P=0.03). Consequently, an exercise training program in adjunct to pharmacotherapy provides higher weight reduction and fat mass loss in obesity treatment. It also seems to have further beneficial effects on leptin resistance, as indicated by decreases in leptin levels expressed per kilogram of fat mass.     

Associations of visceral and liver fat with the metabolic syndrome across the spectrum of obesity: the AGES-Reykjavik study

Visceral adipose tissue (VAT) is a key pathogenic fat depot in the metabolic syndrome (MetS), but liver fat (LF) may also play an important role. We evaluated associations of VAT and LF with MetS in normal weight, overweight, and obese men and women (BMI <25, 25-29.9, and ≥30 kg/m2, respectively). This analysis included 2,495 participants from the Age, Gene/Environment Susceptibility (AGES)-Reykjavik study with computed tomography measurements for VAT and LF. MetS was defined by ≥3 of the following: larger abdominal circumference, hypertension, elevated triglyceride (TG), low high-density lipoprotein (HDL), impaired fasting glucose (IFG), and microalbuminuria. We estimated the odds of MetS per 1-s.d. increase in VAT and LF, adjusting for key covariates. VAT was associated with an increased odds of MetS in normal weight, overweight, and obese women (odds ratios (OR) = 2.78, 1.63, and 1.43, respectively; all P < 0.01) that diminished in magnitude with increasing BMI (VAT × BMI class interaction P < 0.001). In men, VAT was related to MetS only among the overweight (OR = 1.69, P < 0.01). LF was associated with MetS in the overweight and obese groups in women (OR = 1.38 and 1.45; both P < 0.001) and in men (OR = 1.38, P = 0.01; and OR = 1.27, P = 0.10), but not in the normal weight groups. These BMI-specific relationships persisted when both fat depots were included in the model. VAT and LF were associated with MetS independently of each other, and these relationships were modified by BMI class such that, VAT was the more important depot at lower levels of obesity and LF at higher levels. Importantly, fatty liver may be a novel metabolic risk factor in overweight and obese individuals.     

Nocturnal growth hormone secretory dynamics are altered after resistance exercise: deconvolution analysis of 12-hour immunofunctional and immunoreactive isoforms

To characterize the effects of daytime exercise on subsequent overnight growth hormone (GH) secretion and elimination dynamics, serum was sampled, and GH was measured every 10 min for 12 h (1800 to 0600) in a control (CON) condition and after a 50-set resistance exercise protocol (EX) from 1500 to 1700. GH was measured with a conventional immunoreactive (IR) and an immunofunctional (IF) assay, and values were analyzed via a multi-parameter deconvolution analysis. EX resulted in a higher overnight secretory burst frequency [CON: 7.6 (SD 2.4) < EX: 9.4 (2.2) bursts per 12 h, P = 0.005] but lower mean burst mass [CON: 9.2 (4.7) > EX: 6.0 (2.9) microg/l, P = 0.019] and secretory rate [CON: 0.68 (0.29) > EX: 0.48 (0.23) microg/l/min; P = 0.015; ANOVA main effect means presented]. Approximate entropy (ApEn) was greater after EX, indicating a less orderly GH release process than CON. The estimated half-life of IF GH was significantly lower than IR GH [IF: 15.3 (1.1) < IR 19.8 (1.6) min, P < 0.001] but similar between the CON and EX conditions (approximately 17 min). Despite the changes in secretory dynamics, 12-h mean and integrated GH concentrations were similar between conditions. The results suggest that although quantitatively similar total amounts of GH are secreted overnight in CON and EX conditions, resistance exercise alters the dynamics of secretion by attenuating burst mass and amplitude yet increasing burst frequency.     

High-fat hypocaloric diet modifies carbohydrate utilization of obese rats during weight loss

The effects of fat content in the hypocaloric diet on whole body glucose oxidation and adipocyte glucose transport were investigated in two animal-feeding experiments. Diet-induced obese rats were food restricted to 75% of their previous energy intakes with either a high (45% by calorie) or a low (12% by calorie) corn oil diet for 9 wk (experiment 1) or 10 days (experiment 2). The losses of body weight (P < 0.05) and adipose depot weight (P < 0.05) were less in the 45% compared with the 12% fat group. During the dynamic phase of weight loss (day 10 of food restriction), plasma glucose and insulin concentrations were higher (P < 0.05) in the 45% than those in the 12% fat group. Whole body carbohydrate oxidation rate in response to an oral load of glucose was increased (P < 0.001) by food restriction in both dietary groups; however, carbohydrate oxidation rates were lower (P < 0.01) in the 45% than in the 12% fat-fed rats during the weight loss period. Adipocyte glucose transport was greater (P < 0.02) in the 45% than in the 12% fat group in an intra-abdominal adipose depot but not in subcutaneous fat. These data suggest that dietary fat content modifies whole body glucose oxidation and intra-abdominal adipocyte glucose uptake during weight loss.