Weight-reduced Subjects Research Articles

Resistance Training Reduces Skeletal Muscle Work Efficiency in Weight-Reduced and Non-Weight-Reduced Subjects.

Objective:To determine whether resistance training is similarly effective in reducing skeletal muscle efficiency and increasing strength in weight-reduced and maximal weight subjects.Methods:We examined the effects of supervised resistance exercise on skeletal muscle in 14 overweight and obese individuals sustaining a 10% or greater weight loss for over 6 months, and a phenotypically similar group of 15 subjects who were nonweight-reduced and weight stable at their maximal lifetime body weight. We assessed skeletal muscle work efficiency and fuel utilization (bicycle ergometry), strength (dynamometry), body composition (dual energy x-ray absorptiometry), and resting energy expenditure (indirect calorimetry) before and after 12 weeks of thrice weekly resistance training.Results:Non-weight-reduced subjects were significantly (10–20%) stronger before and after the intervention than reduced weight subjects and gained significantly more fat-free mass with a greater decline in % body fat than weight-reduced subjects. Resistance training resulted in similar significant decreases (~10 %) in skeletal muscle work efficiency at low level exercise and ~10–20% increases in leg strength in both weight-reduced and non-weight-reduced subjects.Conclusion:Resistance training similarly increases muscle strength and decreases efficiency regardless of weight loss history. Increased resistance training could be an effective adjunct to reduced-weight maintenance therapy.

Triiodothyronine and leptin repletion in humans similarly reverse weight-loss-induced changes in skeletal muscle.

Subjects maintaining a ≥10% dietary weight loss exhibit decreased circulating concentrations of bioactive thyroid hormones and increased skeletal muscle work efficiency largely due to increased expression of more-efficient myosin heavy chain (MHC) isoforms (MHC I) and significantly mediated by the adipocyte-derived hormone leptin. The primary purpose of this study was to examine the effects of triiodothyronine (T3) repletion on energy homeostasis and skeletal muscle physiology in weight-reduced subjects and to compare these results with the effects of leptin repletion. Nine healthy in-patients with obesity were studied at usual weight (Wtinitial) and following a 10% dietary weight loss while receiving 5 wk of a placebo (Wt-10%placebo) or T3 (Wt-10%T3) in a single-blind crossover design. Primary outcome variables were skeletal muscle work efficiency and vastus lateralis muscle mRNA expression. These results were compared with the effects of leptin repletion in a population of 22 subjects, some of whom participated in a previous study. At Wt-10%placebo, skeletal muscle work efficiency and relative expression of the more-efficient/less-efficient MHC I/MHC II isoforms were significantly increased and the ratio of the less-efficient to the more-efficient sarco(endo)plasmic reticulum Ca2+-ATPase isoforms (SERCA1/SERCA2) was significantly decreased. These changes were largely reversed by T3 repletion to a degree similar to the changes that occurred with leptin repletion. These data support the hypothesis that the effects of leptin on energy expenditure in weight-reduced individuals are largely mediated by T3 and suggest that further study of the possible role of thyroid hormone repletion as adjunctive therapy to help sustain weight loss is needed.

Impact of body-composition methodology on the composition of weight loss and weight gain

We intended to (i) to compare the composition of weight loss and weight gain using densitometry, deuterium dilution (D₂O), dual-energy X-ray absorptiometry (DXA), magnetic resonance imaging (MRI) and the four-compartment (4C) model and (ii) to compare regional changes in fat mass (FM), fat-free mass (FFM) and skeletal muscle as assessed by DXA and MRI. Eighty-three study participants aged between 21 and 58 years with a body mass index range of 20.2-46.8 kg/m(2) had been assessed at two different occasions with a mean follow-up between 23.5 and 43.5 months. Body-weight changes within < 3% were considered as weight stable, a gain or a loss of >3% of initial weight was considered as a significant weight change. There was a considerable bias between the body-composition data obtained by the individual methods. When compared with the 4C model, mean bias of D₂O and densitometry was explained by the erroneous assumption of a constant hydration of FFM, thus, changes in FM were underestimated by D₂O but overestimated by densitometry. Because hydration does not normalize after weight loss, all two-component models have a systematic error in weight-reduced subjects. The bias between 4C model and DXA was mainly explained by FM% at baseline, whereas FFM hydration contributed to additional 5%. As to the regional changes in body composition, DXA data had a considerable bias and, thus, cannot replace MRI. To assess changes in body composition associated with weight changes, only the 4C model and MRI can be used with confidence.

Dynamics of Change in Total and Regional Body Composition After Gastric Bypass in Obese Patients

Little is known on patterns of change over time in body composition, especially lean body mass (LBM), during massive weight loss after Roux-en-Y gastric bypass (RYGB) in obese patients. We performed sequential measurements of total and regional body composition in patients after RYGB, and we compared a subsample of patients after surgery to a nonsurgical control group of similar age and body fatness. We used dual-energy X-ray absorptiometry (DXA) before and at 3, 6, and 12 months after RYGB in 42 obese women (before surgery: age 39.5 +/- 11.6 years; BMI 44.6 +/- 6.1 kg/m(2); mean +/- s.d.) and in 48 control obese women referred for nonsurgical weight management, before weight loss. During 1-year follow-up after RYGB, there was a continuous decrease in body weight (-36.0 +/- 12.5 kg at 1 year), total fat mass (FM) (-26.0 +/- 9.1 kg), as well as in trunk and appendicular FM. In contrast, the decrease in total LBM (-9.8 +/- 4.8 kg at 1 year), as well as in trunk and appendicular LBM, plateaued after 3-6 months. Rates of loss in weight, FM, and LBM were highest during the first 3-month period after RYGB (6.4 +/- 1.8, 4.1 +/- 1.7, and 2.3 +/- 1.2 kg/month, respectively), then decreased continuously for FM but plateaued for LBM. There was no evidence of a decrease in total, trunk, or appendicular LBM in weight-reduced subjects compared to the control group. In conclusion, follow-up of these obese women revealed a differential pattern of change in FM and LBM after RYGB. Despite an important loss in LBM, especially during the 3-6 months of initial period, LBM appears to be spared thereafter.

Is Lean Body Mass Decreased after Obesity Treatment by Adjustable Gastric Banding?

There is concern that surgically-induced weight loss in obese subjects is associated with a disproportionate decrease in lean body mass (LBM) and in skeletal muscle mass (SMM), a major constituent of LBM. To address this issue, 1) we measured total and regional body composition following gastric banding in a group of obese subjects, and 2) we compared these data to those of a non-surgical control group of similar age and body size. Body composition was assessed by dual-energy X-ray absorptiometry (DEXA) before and after laparoscopic adjustable silicone gastric banding (LAGB) in 32 women (after 1 year: age 43.7+/-8.4 years, BMI 36.4+/-5.9 kg/m2, mean+/-SD), and in 117 control women (age 44.5+/-7.5 years; BMI 36.7+/-5.5 kg/m2) referred for non-surgical weight management, prior to weight loss. SMM was estimated using a published equation based on LBM of the extremities (appendicular LBM). 1 year after LAGB, body weight loss (-23.7+/-11.6 kg, P<10(-6)) was mainly due to decreased fat mass (-21.2+/-11.2 kg, P<10(-6)), and total LBM was modestly, although significantly, decreased (-2.1+/-4.2 kg, P=0.01). Appendicular LBM (-0.7+/-2.7 kg) and total SMM (-0.9+/-3.0 kg) were not significantly modified. None of the body composition variables was significantly decreased in weight-reduced subjects compared to the control group, especially appendicular LBM and total SMM. Results provide no evidence for a decrease in appendicular LBM and total SMM with weight loss following LAGB. Follow-up of these obese patients revealed a very favorable pattern of change in total and regional body composition, with preservation of muscle mass.

Effect of significant intermediate-term weight loss on serum leptin levels and body composition in severely obese subjects.

Leptin, produced by adipose tissue, signals body fat content to the hypothalamus. Serum leptin levels (SLL), elevated in obese humans, decrease with weight loss. This study investigated the reduction of SLL and fat mass following restrictive bariatric surgery. Obese subjects (body mass index [BMI] >35 kg/m2, n=154) undergoing gastric banding (weight-reduced subjects) were investigated for SLL and body composition before surgery and for 2 years after. Overweight subjects matched for fat mass and gender (fat mass-matched overweight controls, n=194) and subjects who had never been obese (normal weight controls, n=158) were studied for comparison. SLL were highest in weight-reduced subjects and decreased with weight loss (P <0.001), remaining elevated compared with normal weight controls (P <0.001) but lower than fat mass-matched overweight controls (women: P <0.04). At 2 years, SLL normalized for fat mass (allowing comparison between various levels of adiposity) were lower in weight-reduced subjects compared with fat mass-matched overweight controls (women: P =0.003), yet were similar for weight-reduced subjects at 2 years compared with normal weight controls despite 14 kg greater fat mass. Relative lean mass of extremities in weight-reduced subjects increased with weight loss (P <0.001). SLL decreased after considerable weight loss more than could be accounted for by fat mass or BMI reduction alone. This disproportionate decrease in SLL might point to a mechanism that evolved as adaptation to starvation during times of famine. Thus, post-obese subjects may be at risk of weight-regain due to disproportionately low SLL and increased appetite via the leptin-melanocortin pathway.

Effects of obesity and weight loss on the expression of proteins involved in fatty acid metabolism in human adipose tissue.

Disturbances in adipocyte lipolysis in obesity may contribute to elevated circulating non-esterified fatty acid (NEFA) concentrations and insulin resistance. In experimental models, NEFA metabolism is influenced by adipocyte proteins such as adipocyte and keratinocyte lipid binding proteins (aP2/ALBP and mal1/KLBP) and fatty acid translocase (CD36). We investigated the effect of obesity and weight loss on the expression of these proteins in human subcutaneous adipose tissue. Subcutaneous adipose tissue was obtained from 12 obese (body mass index (BMI) 42.4+/-1.6 kg/m(2)) and 12 lean (23.4+/-0.6 kg/m(2)) subjects. The obese subjects underwent gastric banding and biopsies were taken again after 2 y following a significant weight reduction (BMI 32.8+/-1.4 kg/m(2)). Adipose tissue proteins were quantified by Western blotting. Differential expression of ALBP, KLBP and CD36 was observed in lean and weight-reduced subjects compared with obese individuals. This resulted in a significantly lower ALBP/KLBP ratio in lean and weight-reduced individuals compared to obese subjects. Furthermore there was a significant influence of gender on this ratio. Moreover, the commonly used internal standard protein actin was expressed significantly higher in lean compared to obese individuals. The relative content of ALBP and KLBP in human adipose tissue changes with obesity, weight loss and gender indicating differential regulation. Differing responses in the expression patterns of adipose tissue proteins capable of binding NEFAs in response to weight changes suggest a potential importance in the development of obesity-associated complications.

Effects of obesity and stable weight reduction on UCP2 and UCP3 gene expression in humans.

The molecular determinants of energy expenditure are presently unknown. Recently, two uncoupling protein homologues, UCP2 and UCP3, have been identified. UCP2 is expressed widely, and UCP3 is expressed abundantly in skeletal muscle. Both could be important regulators of energy balance. In this paper, we investigated whether altered UCP2 and UCP3 mRNA levels are associated with obesity or weight reduction. UCP2, UCP3 long and short mRNA levels were examined in skeletal muscle and in white adipose tissue of lean, obese, and weight-reduced individuals by RNase protection assay. Expression of UCP2, UCP3S, and UCP3L mRNA in skeletal muscle was similar in lean individuals and in individuals with obesity at stable weight. In contrast, UCP3L and UCP3S mRNAs were decreased by 38% (p<0.0059) and 48% (p<0.0047), respectively, in 20% weight-reduced patients with obesity at stable weight. In contrast, UCP2 mRNA levels were increased by 30% in skeletal muscle of 20% weight-reduced subjects with obesity. In a different set of patients, mostly lean, UCP3L mRNA in skeletal muscle was decreased by 28% (p = 0.0425) after 10% weight reduction at stable weight. Expression of UCP2 mRNA in subcutaneous adipose tissue was similar in lean individuals and in individuals with obesity, and was increased by 58% during active weight loss. Stabilization at reduced body weight in humans is associated with a decrease in UCP3 mRNA in muscle. It is possible that reduced UCP3 expression could contribute to decreased energy expenditure in weight-stable, weight-reduced individuals.

Effects of body weight and food intake on pleasantness ratings for a sweet stimulus.

A physiological role for pleasure has been suggested from observations that glucose loads reduced pleasantness ratings for sweet stimuli in normal weight but not in weight-reduced subjects. This hypothesis was reexamined in fasting and food-loaded, lean and obese subjects. Magnitude estimates of sweetness and pleasantness were obtained for seven sucrose concentrations. Indices of obesity including percent overweight, percent body fat, and body mass index were calculated. Pleasantness ratings of fasting subjects either increased up to a moderate concentration and then declined (type I hedonic response) or increased monotonically with concentration (type II hedonic response). Both types of response were found in lean and obese subjects. Within each weight group there appeared a negative correlation between pleasantness response and indices of obesity. Caloric loads reduced hedonic ratings of type II lean and obese subjects, but did not affect pleasantness response of type I lean and obese subjects. These findings indicate the presence of an hedonic monitor biased by body weight and caloric intake. The data suggest a physiological role for pleasure in regulating body weight at different set points in lean and obese subjects.