The Lap-Band is an effective tool for weight loss even in the United States.

BACKGROUND: Despite impressive results with the Lap-Band in Europe and Australia, the early Food and Drug Administration A trial in the United States showed fairly poor results. This prospective study attempts to determine if the Lap-Band can produce effective weight loss in morbidly obese Americans. METHODS: Five hundred four consecutive patients have undergone placement of the Lap-Band (Inamed). Four hundred fourteen patients were women (82%) and 90 were men (18%). The median preoperative weight was 138 kg, and the preoperative median body mass was 49 kg/m(2). RESULTS: Five hundred two bands were placed laparoscopically. One was converted to an open procedure because of lack of exposure, and one was placed open because of multiple previous abdominal surgeries. Median operating time was 50 minutes, and median length of stay was 1.8 days. Percent excess weight loss at 6, 12, 24, and 36 months for all patients was 36%, 50%, 61%, and 65%, respectively. Complications occurred in 96 patients (19%) primarily consisting of port tubing separations, slips, postoperative dysphagia, and port infections. There was one (.2%) mortality. CONCLUSIONS: The Lap-Band system is an effective tool for weight loss surgery in morbidly obese patients in the United States.

Comparison of methods for assessing body composition changes during weight loss.

PURPOSE: Four cross-sectional studies have reported that percent body fat (%BF) measured by dual-energy x-ray absorptiometry (DXA) is significantly higher compared with values obtained with air displacement plethysmography (ADP) using the Bod Pod(R) in normal-weight individuals. This study was performed to confirm these findings in an overweight population and to assess whether DXA and ADP detected similar changes in body composition after moderate weight loss. METHODS: Twelve women (42 +/- 8 yr) and 10 men (40 +/- 11 yr) had their %BF, fat mass (FM), and fat-free mass (FFM) measured using DXA and ADP before and after an 8-wk weight-loss program involving moderate energy restriction and exercise. RESULTS: Body weight decreased significantly in women (-4.3 +/- 3.4 kg) and men (-4.7 +/- 3.1 kg). There were significant method (ADP vs DXA) and time (pre and post) effects but no method by time or gender interactions. Methods were significantly different in estimating %BF, FM, and FFM with ADP estimates of %BF and FM being lower and estimates of FFM higher than corresponding DXA values (P = 0.000). There were significant correlations accounting for a high degree of the shared variance between DXA and ADP (r = 0.98 to 0.99) for %BF, FM, and FFM and lower correlations for the changes in %BF (r = 0.66), FM (r = 0.86), and FFM (r = 0.34). In response to weight loss, the mean changes in %BF, FM, and FFM were not significantly different between methods (P > 0.05). CONCLUSION: Both DXA and ADP measure changes in body composition after small to moderate weight loss to the same extent and with similar sensitivity.

Application of a flexible synthesis of (5R)-thiolactomycin to develop new inhibitors of type I fatty acid synthase.

Fatty acid synthase (FAS) catalyzes the synthesis of palmitate from the sequential condensation of an acetyl primer with two carbon units added from malonyl-CoA. Inhibition of the beta-ketoacyl synthase domain of mammalian FAS leads to selective cytotoxicity to various cancer cell lines in vitro and in vivo. Also, inhibitors of FAS can cause reduced food intake and body weight in mice. Naturally occurring thiolactomycin (TLM) was used as a template to develop a new class of type I FAS inhibitors. Using a flexible synthesis, families of TLM structural analogues were obtained that possess selective FAS activity and display anticancer and weight loss effects. Compounds 13a and 13d inhibit pure FAS (ZR-75-1 breast cancer, IC(50) = <or=20 microg/mL), are nontoxic (MCF-7, IC(50) = >50 microg/mL), and display effective weight loss in BalbC mice (>5%). Another subclass of TLM derivatives (23b-d, 31a) exhibits FAS activity (IC(50) = <or=15 microg/mL), causes weight loss (>5%), and is cytotoxic to cancer cells (IC(50) < 38 microg/mL). Finally, a third subclass (16b, 29, 30) is also active against FAS (IC(50) = <or=20 microg/mL), is cytotoxic to cancer cells (IC(50) < 25 mg/mL), and does not cause weight loss in BalbC mice. These studies identify thiolactomycin as a promising template for the development of new selective cancer and obesity treatments.

The U.S. experience with implantable gastric stimulation (IGS) for the treatment of obesity - update on the ongoing clinical trials.

BACKGROUND: The prevalence of obesity is growing worldwide. Medical therapies are often ineffective, and surgical treatments have significant risk. IGS(R) offers a novel approach to weight loss that was found to be safe and effective in European trials. In the U.S., 2 consecutive trials have been undertaken. METHODS: In 2000, a multicenter, prospective, randomized, placebo-controlled trial involving 103 morbidly obese patients (U.S. O-01) was undertaken. In 2002, a prospective, open label trial involving 30 morbidly obese patients was initiated (DIGEST). Patients were followed for complications, postoperative untoward events, and weight loss. RESULTS: In O-01, there were no significant perioperative complications. However, 20 patients were found to have had lead dislodgements. At 7 months, there was no significant difference in weight loss between the activated and non-activated groups. After 29 months, loss of excess weight (EWL) approached 20%. With DIGEST, there was 1 operative complication (a lost needle retrieved surgically). There were no untoward events or known lead dislodgements. EWL was 23% after only 16 months follow-up. With the introduction of a preoperative screening algorithm, almost 40% EWL was achieved for selected patients in both trials. CONCLUSIONS: In the U.S., the IGS system for the treatment of obesity has been shown to be safe. Technical improvements and better patient selection resulted in improved weight loss. The preliminary results of these trials suggest that IGS may be a suitable surgical option for selected patients.

Adiponectin levels do not change with moderate dietary induced weight loss and exercise in obese postmenopausal women.

OBJECTIVE: The purpose of this study was to determine changes in adiponectin levels with moderate weight loss, weight loss plus aerobic exercise, or weight loss plus resistive exercise in overweight and obese, sedentary postmenopausal women. DESIGN: Longitudinal, clinical intervention study of 6-month (3 x /week) program of either weight loss (WL, n=15), weight loss + aerobic exercise (WL+AEX, n=16), or weight loss + resistive exercise (WL+RT, n=9) SUBJECTS: We studied 40 sedentary, overweight and obese (body mass index, BMI=32+/-1 kg/m(2), X+/-s.e.m.) postmenopausal (57+/-1y) women. MEASUREMENTS: Fat mass and fat-free mass (FFM) by dual-energy X-ray absorptiometry, plasma insulin, leptin, and adiponectin by radioimmunoassay. RESULTS: Age, body weight, BMI, waist and hip circumferences, waist-to-hip ratio, VO(2)max, percent fat, total body fat mass, FFM, and fasting plasma glucose, insulin, leptin, and adiponectin concentrations were similar among WL, WL+AEX, and WL+RT groups before the interventions. In all women combined, body weight, BMI, and waist and hip circumferences decreased (P < 0.001). There was a significant absolute decrease in percent body fat from 47 to 44%, representing a 13% decrease in total fat mass and a -1.6% change in FFM. Fasting concentrations of plasma adiponectin did not change (40+/-16%, P=NS), whereas fasting plasma glucose, insulin, and leptin all decreased (P<0.001). CONCLUSIONS: Plasma adiponectin levels do not change with a 6-month moderate weight reduction program even when accompanied by aerobic or resistive exercise training in overweight and obese postmenopausal women.

Changes in lipoprotein(a) levels and hormonal correlations during a weight reduction program.

BACKGROUND AND AIM: To examine the effects of a weight reduction program on serum lipoprotein(a) [Lp(a)] levels and investigate whether the hormonal modifications occurring during weight loss may explain the changes in Lp(a) levels. METHODS AND RESULTS: This longitudinal clinical intervention study of a low-calorie diet involved 62 healthy obese patients (21 men aged 32 +/- 9.6 years and 41 women aged 37 +/- 14.6 years). Their anthropometric parameters (weight, height, body mass index, waist-to-hip ratio), fasting serum lipid levels, hormones (total testosterone, estradiol, total triiodothyronine, insulin), sex hormone binding globulin (SHBG) and blood sugar levels were determined at baseline and after six weeks of dietary treatment. A 7.5% loss in initial body weight was achieved and there was a statistically significant decrease in serum total cholesterol, LDL-cholesterol, HDL-cholesterol and triglycerides (p < 0.001). No changes in Lp(a) levels were observed in the study population as a whole, but there was a 17.6% (p < 0.05) reduction in the subjects with high pre-treatment Lp(a) values (> 20 mg/dL). The decrease in Lp(a) levels closely correlated with initial Lp(a) levels (r = 0.81 p < 0.001), but did not correlate with changes in anthropometric parameters or the hormonal modifications occurring during the weight loss. CONCLUSIONS: A low-calorie diet associated with weight loss in obese subjects may have beneficial effects on serum Lp(a) levels in patients with high pre-treatment Lp(a) concentrations. This effect seems to be independent of the hormonal changes observed during weight loss.

Resistin and adiponectin expression in visceral fat of obese rats: effect of weight loss.

OBJECTIVE: Obesity-related insulin resistance is closely associated with visceral fat accumulation. Several adipocyte-secreted molecules have been implicated in the development of type 2 diabetes, among them, the recently discovered adiponectin and resistin proteins. Some of these adipocytokines are also present in the immune system, thus suggesting an intriguing functional connection. RESEARCH METHODS AND PROCEDURES: We determined adiponectin and resistin expressions in visceral (VAT) and subcutaneous adipose tissue of lean and obese Zucker (fa/fa) rats using reverse-transcription polymerase chain reaction. Moreover, we analyzed the variations after body-weight reduction in food-restricted obese rats. RESULTS: Resistin and adiponectin expression was significantly lower in VAT of genetically obese in comparison with lean rats; no differences were observed when subcutaneous adipose tissues of the same animals were compared. weight loss resulted in an increase of adiponectin expression in VAT, whereas a further significant decrease in resistin mRNA level was observed. Resistin is also present and equally expressed in splenocytes of lean and obese rats. DISCUSSION: Adiponectin and resistin are down-regulated in VAT of obese rats. Adiponectin expression is restored to normal levels after body-weight reduction, supporting its link with obesity-related insulin resistance. On the contrary, the further decrease of resistin mRNA after weight loss does not support the hypothesis that resistin may play a causative role in insulin resistance in obese rats. Moreover, we demonstrated the presence of resistin in immunocompetent cells in both humans and rats, thus adding another factor to the list of molecules that adipose tissue shares with the immune system.

Therapeutic Options in Nonalcoholic Fatty Liver Disease.

Nonalcoholic fatty liver disease, an entity that includes nonalcoholic steatohepatitis, is typically a benign, indolent condition. However, in a subset of patients, the clinical course may progress to advanced cirrhosis, end-stage liver disease, or hepatocellular carcinoma. Unfortunately, the pathogenesis, natural history, and potential therapies for these disorders remain poorly understood. Identifying patients who should be targeted for potential treatment remains difficult. Liver biopsy should be considered to assess the degree of hepatic inflammation and fibrosis, because physical examination findings, biochemical parameters, and the results of radiographic studies have been shown to correlate poorly with the severity of steatohepatitis and fibrosis. Although there is some evidence suggesting that obesity, diabetes mellitus, older age, and perhaps an aspartate transaminase:alanine aminotransaminase ratio higher than 1 may be predictors of more advanced fibrosis, histology remains the gold standard. Most patients with simple hepatic steatosis appear to follow a benign course and probably do not require aggressive therapy. Conversely, patients with steatohepatitis with extensive inflammation and fibrosis are the patients who are most likely to benefit from effective therapies. The most commonly recommended treatment is weight loss. Existing data suggest that rapid weight loss may promote hepatic inflammation and fibrosis; therefore, gradual weight loss should be recommended. Large, randomized, controlled trials evaluating the long-term histologic impact and clinical outcomes of weight loss strategies are lacking. Potentially promising pharmacologic therapies include insulin-sensitizing oral hypoglycemic agents such as metformin and the thiazolidenediols, antihyperlipidemic agents such as gemfibrozil or 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, vitamin E and other antioxidants, ursodeoxycholic acid, and betaine. As with weight loss, data regarding the efficacy of these pharmacologic options are limited. In addition, there are no widely accepted guidelines to help direct the clinician in the optimal use of these agents in patients with nonalcoholic fatty liver diseases.