Effect of weight loss on insulin sensitivity and intramuscular long-chain fatty acyl-CoAs in morbidly obese subjects.

Increases in intramyocellular long-chain fatty acyl-CoAs (LCACoA) have been implicated in the pathogenesis of insulin resistance in skeletal muscle. To test this hypothesis, we measured muscle (vastus lateralis) LCACoA content and insulin action in morbidly obese patients (n = 11) before and after weight loss (gastric bypass surgery). The intervention produced significant weight loss (142.3 +/- 6.8 vs. 79.6 +/- 4.1 kg for before versus after surgery, respectively). Fasting insulin decreased by approximately 84% (23.3 +/- 3.8 vs. 3.8 +/- 0.5 mU/ml), and insulin sensitivity, as determined by minimal model, increased by approximately 360% (1.2 +/- 0.3 vs. 4.1 +/- 0.5 min(-1). [ micro U/kg(-1)]) indicating enhanced insulin action. Muscle palmityl CoA (16:0; 0.54 +/- 0.08 vs. 0.35 +/- 0.04 nmol/g wet wt) concentration decreased by approximately 35% (P < 0.05) with weight loss, whereas stearate CoA (18:0; -17%; 0.65 +/- 0.05 vs. 0.54 +/- 0.03 nmol/g wet wt) and linoleate CoA (18:2; -30%; 2.47 +/- 0.27 vs. 1.66 +/- 0.19 nmol/g wet wt) were also reduced (P < 0.05). There were no statistically significant declines in muscle palmitoleate CoA (16:1), oleate CoA (18:1), or total LCACoA content. These data suggest that a reduction in intramuscular LCACoA content may be responsible, at least in part, for the enhanced insulin action observed with weight loss in obese individuals.

High failure rate after laparoscopic adjustable silicone gastric banding for treatment of morbid obesity.

OBJECTIVE: To report the results from one of the eight original U.S. centers performing laparoscopic adjustable silicone gastric banding (LASGB), a new minimally invasive surgical technique for treatment of morbid obesity. SUMMARY BACKGROUND DATA: Laparoscopic adjustable silicone gastric banding is under evaluation by the Food & Drug Administration in the United States in an initial cohort of 300 patients. METHODS: Of 37 patients undergoing laparoscopic placement of the LASGB device, successful placement occurred in 36 from March 1996 to May 1998. Patients have been followed up for up to 4 years. RESULTS: Five patients (14%) have been lost to follow-up for more than 2 years but at last available follow-up (3-18 months after surgery) had achieved only 18% (range 5-38%) excess weight loss. African American patients had poor weight loss after LASGB compared with whites. The LASGB devices were removed in 15 (41%) patients 10 days to 42 months after surgery. Four patients underwent simple removal; 11 were converted to gastric bypass. The most common reason for removal was inadequate weight loss in the presence of a functioning band. The primary reasons for removal in others were infection, leakage from the inflatable silicone ring causing inadequate weight loss, or band slippage. The patients with band slippage had concomitant poor weight loss. Bands were removed in two others as a result of symptoms related to esophageal dilatation. In 18 of 25 patients (71%) who underwent preoperative and long-term postoperative contrast evaluation, a significantly increased esophageal diameter developed; of these, 13 (72%) had prominent dysphagia, vomiting, or reflux symptoms. Of the remaining 21 patients with bands, 8 currently desire removal and conversion to gastric bypass for inadequate weight loss. Six of the remaining patients have persistent morbid obesity at least 2 years after surgery but refuse to undergo further surgery or claim to be satisfied with the results. Overall, only four patients achieved a body-mass index of less than 35 and/or at least a 50% reduction in excess weight. Thus, the overall need for band removal and conversion to GBP in this series will ultimately exceed 50%. CONCLUSIONS: The authors did not find LASGB to be an effective procedure for the surgical treatment of morbid obesity. Complications after LASGB include esophageal dilatation, band leakage, infection, erosion, and slippage. Inadequate weight loss is common, particularly in African American patients. More study is required to determine the long-term efficacy of the LASGB

Energy restriction reduces fractional calcium absorption in mature obese and lean rats.

weight loss is associated with bone loss and the risk may be greater in lean than heavier individuals, but the mechanisms involved remain unclear. We hypothesized that energy restriction (EnR) would decrease true fractional Ca absorption (TFCA) and be mediated by Ca-regulating hormones, but differently in obese and lean rats. Rats were fed a high fat (47% energy) or low fat (16% energy) diet for 4 mo. At 6 mo of age, the resulting lean [284 +/- 28g (mean +/- SD, n = 18)] and obese (319 +/- 34g, n = 20) groups (P < 0.005) were divided into controls (CTL, ad libitum) and energy-restricted (40% restriction) groups. At baseline, bone resorption (urinary crosslinks) was higher and bone formation (serum osteocalcin) was lower in obese than in lean rats, whereas Ca balance components and Ca-regulating hormones did not differ. EnR for 10 wk reduced body weight by 25 +/- 7% compared with a 6 +/- 6% gain in CTL rats (P < 0.001). For both lean and obese rats, TFCA (5-d measurement, (45)Ca radioisotope) decreased from 30 +/- 9% to 24 +/- 9% with EnR, compared with 25 +/- 10% to 29 +/- 11% in controls (P < 0.05). weight loss was directly correlated with the decrease in TFCA (r = 0.34, P < 0.05). Uterine weights indicated a reduced estrogenic activity in energy-restricted rats (P < 0.0001). In lean, but not obese rats, serum estradiol (E(2)) correlated with weight loss (r = 0.52, P < 0.05), and tended to correlate with the decrease in TFCA (r = 0.48, P = 0.06). At the end of the study, serum 25-hydroxyvitamin-D was lower and urinary Ca was higher in lean than obese energy-restricted rats. Distinct endocrine profiles during weight loss in obese and lean rats suggest that the susceptibility of bone and Ca metabolism to EnR could differ depending on initial body weight.

Comparison of efficacy of Sibutramine ( Meridia ) or Orlistat ( Xenical ) versus their combination in obese women.

OBJECTIVE: Sibutramine ( Meridia ) and Orlistat ( Xenical ) are currently used for weight loss. We aimed to investigate the effect of Orlistat ( Xenical ) and Sibutramine ( Meridia ) combination therapy in treatment of obese women. SUBJECTS AND DESIGN: Study population consisted of 89 obese women who had a body mass index > or = 30 kg/m2, were normotensive, and had normal glucose tolerance. All patients were placed on a diet which contained fat approximately 30% of total calorie intake and the diet was designed to cause an energy deficit of approximately 2.51-3.56 megajoule/day. At the first month of diet (baseline), all patients were randomly divided into three therapy groups: Diet + Orlistat ( Xenical ) (group 1; n = 30 patients), Diet + Sibutramine ( Meridia ) (group 2; n = 29 patients), Diet + Orlistat ( Xenical ) + Sibutramine ( Meridia ) (group 3; n = 30 patients). Body weight, body fat distribution and serum lipid levels were evaluated baseline and after six months in all subjects. RESULTS: Mean weight loss was 5.5 +/- 4.9 kg (p = 0.024) in group 1, 10.1 +/- 3.6 kg (p < 0.001) in group 2, 10.8 +/- 6.6 kg (p < 0.001) in group 3 after the six months. weight loss was significantly greater in group 2 (p = 0.003) and group 3 (p = 0.002) when compared with group 1. Percentage of mean weight loss was 5.5 +/- 3.1% in group 1, 10.2 +/- 4.8% in group 2, 10.6 +/- 5.7% in group 3. Percentage of weight loss was higher in group 2 (p = 0.01) and group 3 (p = 0.009) when compared with group 1. weight loss and percentage of weight loss were not different between group 2 and group 3. CONCLUSION: These three regimens had different results on weight loss in obese women. Combination drug therapy and Sibutramine ( Meridia ) therapy were both more effective than Orlistat ( Xenical ) therapy alone. However, no significant difference was noted between combination drug therapy and Sibutramine ( Meridia ) treatment groups.