Enhanced metabolic efficiency contributes to weight regain after weight loss in obesity-prone rats.

Metabolic adjustments occur with weight loss that may contribute to a high rate of weight regain. We have previously observed in obesity-prone, obese rats that weight reduction is accompanied by a suppression in resting metabolic rate beyond what would be predicted for the change in metabolic mass. In the present study, we examine if this adjustment in metabolic efficiency is affected by the length of time in weight maintenance and if it contributes to the propensity to regain after weight loss. Twenty-four-hour, nonresting, and resting energy expenditure (REE) were obtained by indirect calorimetry and normalized to metabolic mass estimated by dual-energy X-ray absorptiometry. A 10% loss in body weight in weight-reduced rats was accompanied by a 15% suppression in adjusted REE. This enhancement in metabolic efficiency was not altered with either 8 or 16 wk of weight maintenance, but it did resolve when the forced control of intake was removed and the weight was regained. The rate of weight regain increased with the time in weight maintenance and was exceptionally high early during the relapse period. During this high rate of weight gain, the suppression in REE persists while consumption increases to a level that is higher than when they were obese. In summary, an enhanced metabolic efficiency and an elevated appetite both contribute (60% and 40%, respectively) to a large potential energy imbalance that, when the forcible control of energy intake is relieved, becomes actualized and results in an exceptionally high rate of weight regain.

Patupilone (epothilone B, EPO906) and imatinib (STI571, Glivec) in combination display enhanced antitumour activity in vivo against experimental rat C6 glioma.

PURPOSE: The microtubule-stabilizing agent patupilone (epothilone B, EPO906) and the tyrosine kinase inhibitor imatinib (STI571, Glivec) which primarily inhibits Bcr-Abl, PDGF and c-Kit tyrosine kinase receptors, were combined in vivo to determine if any interaction would occur with respect to antitumour effect and tolerability using rat C6 glioma xenografted into nude mice. METHODS: Patupilone and imatinib were administered alone or in combination at suboptimal doses. Imatinib treatment (orally once daily) was initiated 4 days after s.c. injection of rat C6 glioma cells into athymic nude mice and patupilone administration (i.v. once per week) was started 3 or 4 days after imatinib treatment. RESULTS: As a single agent, imatinib was inactive in the regimens selected (100 mg/kg: T/C 86% and 116%; 200 mg/kg: T/C 68% and 84%; two independent experiments), but well tolerated (gain in body weight and no mortalities). Patupilone weekly monotherapy demonstrated dose-dependent antitumour effects (1 mg/kg: T/C 67% and 70%; 2 mg/kg: T/C 32% and 63%; 4 mg/kg: T/C 3% and 46%). As expected, dose-dependent body weight losses occurred (final body weight changes at 1 mg/kg were -7% and -3%; at 2 mg/kg were -23% and -13%; and at 4 mg/kg were -33% and -15%). Combining 2 mg/kg patupilone and 200 mg/kg per day imatinib in one experiment produced a non-statistically significant trend for an improved antitumour effect over patupilone alone (combination, T/C 9%), while in the second experiment, enhancement was seen with the combination and reached statistical significance versus patupilone alone (combination, T/C 22%; P=0.008). Reduction of the imatinib dose to 100 mg/kg per day resulted in no enhancement of antitumour activity in combination with 2 mg/kg patupilone. Reduction of the patupilone dose to 1 mg/kg resulted in a reduced antitumour effect, and only a trend for synergy with either imatinib dose (combination, T/C 46% and 40%). Pooling the data from the two experiments confirmed a significant synergy for the combination of 2 mg/kg patupilone and 200 mg/kg per day imatinib (P=0.032), and a trend for synergy at the 1 mg/kg patupilone dose. Reduction in the imatinib dose to 100 mg/kg per day resulted only in additivity with either dose of patupilone. Body weight losses were dominated by the effect of patupilone, since no greater body weight loss was observed in the combination groups. CONCLUSION: Combining patupilone with high-dose imatinib produced an increased antitumour effect without affecting the tolerability of treatment in a relatively chemoresistant rat C6 glioma model. Such results indicate that further evaluation is warranted, in particular to elucidate possible mechanisms of combined action.

The Challenge study: theory-based interventions for smoking and weight loss.

Both smokers and overweight persons report frequent efforts to change their behavior. Long-term success, however, is achieved by few. Interventions are needed to improve long-term success in smoking cessation and weight loss. Our research program is designed to address this need and to test a novel conceptualization of health behavior change that is based on the premise that the initiation and the maintenance of behavior change involve different decision processes. Positive expectations about the consequences of behavior change are thought to guide decisions to initiate behavior change, whereas satisfaction with the outcomes afforded by one's behavior guides decisions about maintenance. In the first phase of our research program, we are evaluating the effect people's expectations about the benefits of behavior change have on immediate and long-term behavioral outcomes. Specifically, participants are assigned to either an 'optimistic' treatment condition that emphasizes positive expectations for outcomes or a 'balanced' treatment condition that gives equal weight to the benefits and costs associated with behavior change. The impact of manipulating people's expectations about behavior change will be examined in the areas of smoking cessation and weight loss. Results of these studies will advance research on health behavior change by informing practical and theoretical understanding of the factors that control decisions to initiate a new pattern of behavior and to maintain it.

Impact of advanced age on weight loss and health benefits after laparoscopic gastric bypass.

BACKGROUND: Advanced age is considered a relative contraindication to primary bariatric surgery at some institutions. As life expectancy is steadily increasing and quality of life is improving in our elderly population, we may need to reconsider the health benefits that obese elderly patients can obtain from bariatric surgery. Therefore, we examine the operative outcomes, weight loss, reduction of comorbidities, and medication requirements in patients older than 60 years compared with those younger than 60 years undergoing laparoscopic Roux-en-Y gastric bypass. HYPOTHESIS: The null hypothesis tested in this study is that patients older than 60 years who undergo laparoscopic Roux-en-Y gastric bypass experience a medical benefit not significantly different from that experienced by younger patients in terms of the number of medications and comorbid conditions. METHODS: The number of preoperative and postoperative comorbid conditions and the medications required for those conditions were compared between consecutive patients older than 60 years and those younger than 60 years who underwent Roux-en-Y laparoscopic gastric bypass. Early operative outcomes were also assessed. RESULTS: Analysis of 110 patients younger than 60 years compared with 20 patients older than 60 years revealed no difference in complication rate or length of hospital stay. Younger patients lost more weight and had a significantly greater reduction in body mass index. Younger patients also demonstrated more complete resolution of comorbid conditions, although this difference was not significant. Older patients, who had more comorbid conditions requiring more medication at the time of surgery, experienced a greater medication reduction during follow-up, although this was not statistically significant. CONCLUSIONS: Patients of advanced age can safely undergo laparoscopic Roux-en-Y gastric bypass. Younger patients can be expected to demonstrate greater weight loss and experience more complete resolution of their comorbid conditions. Older patients demonstrated greater overall reduction in medication requirements. Therefore, patients older than 60 years can be considered good candidates for obesity surgery and can be expected to enjoy substantial health benefits similar to those experienced by younger patients.

Effects of weight loss on PLTP activity and HDL particle size.

OBJECTIVE: Dyslipidaemia in obesity is characterized by hypertriglyceridaemia, low HDL-C levels, small, dense HDL particles and increased phospholipid transfer protein (PLTP) activity. METHODS: In the present study, we investigated PLTP activity and HDL particle size in 16 morbidly obese, middle-aged women, who underwent Swedish Adjustable Gastric Banding surgery. Study subjects were tested within 2 months before and 1 y after surgery. PLTP activity was determined by exogenous substrate assay and HDL particle size by gradient gel electrophoresis, respectively. RESULTS: Pronounced weight loss after gastric banding surgery resulted in a significant decrease of PLTP activity from 8.42+/-2.04 to 7.43+/-2.21 micromol/ml/h (P=0.02). The size of HDL(2) particles increased signficantly from 14.04+/-0.86 to 14.28+/-0.64 nm (P=0.02) after body weight reduction, while no change in HDL(3) particle size was apparent. DISCUSSION: Our results suggest that dyslipidaemia in obesity is--at least partially--reversible by weight loss. We hypothesize that reduction of PLTP activity and increase of HDL particle size are important component factors in converting the atherogenic lipoprotein profile of obese subjects into a less atherogenic profile with weight loss.

Increase in skeletal muscle fatty acid binding protein (FABPC) content is directly related to weight loss and to changes in fat oxidation following a very low calorie diet.

AIMS/HYPOTHESIS: There is increasing evidence that intracellular fatty acid binding proteins (FABPc's; 15 kD) function as vehicles of cytosolic fatty acid transport. We studied skeletal muscle cytosolic FABPc, and enzymes reflecting beta-oxidation and oxidative capacity (3-hydroxyacyl-CoA dehydrogenase, HAD, and citrate synthase, CS) in relation to weight loss and changes in substrate utilisation in a group of 35 obese women and obese men with Type II (non-insulin-dependent) diabetes mellitus (women = 27, men = 8). METHODS: Muscle biopsies (vastus lateralis), and measurements of body composition, resting energy expenditure and respiratory exchange ratio were taken before and after dietary intervention (by means of a very low calorie diet). RESULTS: Muscle FABPc tended to increase after diet (178 +/- 13 vs 204 +/- 12 mg x gww(-1), p = 0.06), whereas there were no changes in CS (10.5 +/- 0.7 vs 11.1 +/- 0.6 U x gww(-1)) and HAD (11.2 +/- 0.7 vs 11.7 +/- 0.6 U x gww(-1)). There was a positive relation between the increase in FABPc as result of diet and the amount of weight lost (p < 0.01; adjusted R2, 15.4 %), even when adjusted for mean body weight, and changes in CS and in HAD by partial regression analysis. Interestingly, the increase in FABPc was positively related to increases in resting fat oxidation (adjusted R2, 24 %), even when adjusted for mean resting fat oxidation, and changes in CS and in HAD. CONCLUSION/INTERPRETATION: In conclusion, the ability to increase muscle FABPc could be directly related to weight loss and to changes in fat oxidation following dietary intervention in obesity and Type II (non-insulin-dependent) diabetes mellitus.

Laparoscopic vertical banded gastroplasty for morbid obesity. Assessment of efficacy.

BACKGROUND: The advantages of treating morbidly obese patients via the laparoscopic approach have been demonstrated, in particular, for adjustable silicone gastric banding, but this operation is associated with a high rate of late complications. Gastric bypass and malabsorbitive procedures are feasible via the laparoscopic approach, but they entail a prolonged operating time and a consistently high morbidity rate. Laparoscopic vertical banded gastroplasty represents an effective alternative. METHODS: We performed 250 consecutive LVBG between November 1995 and February 2000. The procedure consisted of a personal technique designed to reproduce, by laparoscopy, MacLean's modification of the standard open Mason vertical-banded gastroplasty, with a calibrated transgastric window, a complete division between the staple lines, and a 5-cm-circumference polypropylene collar. RESULTS: The operative time was 95 min and the conversion rate was 0.8%. Operative mortality was nil; early and late complications, respectively, were 4.4% and 4%; the reoperation rate was 2%. Global results at 4 years were as follows: excess weight loss (EWL) 61%, success rate (excess weight <50%) 76.9%, body mass index (BMI) 29.4 kg/m2. In morbidly obese patients, the EWL at 4 years was 62.2%, with a 77.4% success rate and a 28.4 kg/m2 BMI; in superobese patients, the EWL at 4 years was 54.9% with a 50% success rate and a 35.5 kg/m2 BMI. The overall follow-up rate was 92%. CONCLUSIONS: LVBG is an effective and safe operation in morbidly obese patients, providing good weight loss with a low morbidity rate, no mortality, and minimum discomfort. However, in superobese patients, the weight loss results are disappointing; in these patients, LVBG is questionable and more complex procedures should be considered.

COMPETING DIETARY CLAIMS FOR weight loss: Finding the Forest Through Truculent Trees.

In response to an accelerating obesity pandemic, competing weight-loss diets have propagated; those touting carbohydrate restriction are currently most in vogue. Evidence that sustainable weight loss is enhanced by means other than caloric restriction, however, is lacking. Whereas short-term weight loss is consistently achieved by any dietary approach to the restriction of choice and thereby calories, lasting weight control is not. Competing dietary claims imply that fundamental knowledge of dietary pattern and human health is lacking; an extensive literature belies this notion. The same dietary and lifestyle pattern conducive to health promotion is consistently associated with weight control. A bird's eye view of the literature on diet and weight reveals a forest otherwise difficult to discern through the trees. Competing diet claims are diverting attention and resources from what is actually and urgently needed: a dedicated and concerted effort to make the basic dietary pattern known to support both health and weight control more accessible to all.