Dysfunction of lipid sensor GPR120 leads to obesity in both mouse and human.

Free fatty acids provide an important energy source as nutrients, and act as signalling molecules in various cellular processes. Several G-protein-coupled receptors have been identified as free-fatty-acid receptors important in physiology as well as in several diseases. GPR120 (also known as O3FAR1) functions as a receptor for unsaturated long-chain free fatty acids and has a critical role in various physiological homeostasis mechanisms such as adipogenesis, regulation of appetite and food preference. Here we show that GPR120-deficient mice fed a high-fat diet develop obesity, glucose intolerance and fatty liver with decreased adipocyte differentiation and lipogenesis and enhanced hepatic lipogenesis. Insulin resistance in such mice is associated with reduced insulin signalling and enhanced inflammation in adipose tissue. In human, we show that GPR120 expression in adipose tissue is significantly higher in obese individuals than in lean controls. GPR120 exon sequencing in obese subjects reveals a deleterious non-synonymous mutation (p.R270H) that inhibits GPR120 signalling activity. Furthermore, the p.R270H variant increases the risk of obesity in European populations. Overall, this study demonstrates that the lipid sensor GPR120 has a key role in sensing dietary fat and, therefore, in the control of energy balance in both humans and rodents.

Variation in FTO contributes to childhood obesity and severe adult obesity.

We identified a set of SNPs in the first intron of the FTO (fat mass and obesity associated) gene on chromosome 16q12.2 that is consistently strongly associated with early-onset and severe obesity in both adults and children of European ancestry with an experiment-wise P value of 1.67 x 10(-26) in 2,900 affected individuals and 5,100 controls. The at-risk haplotype yields a proportion of attributable risk of 22% for common obesity. We conclude that FTO contributes to human obesity and hence may be a target for subsequent functional analyses.

The T-381C SNP in BNP gene may be modestly associated with type 2 diabetes: an updated meta-analysis in 49 279 subjects.

A recent study reported an association between the brain natriuretic peptide (BNP) promoter T-381C polymorphism (rs198389) and protection against type 2 diabetes (T2D). As replication in several studies is mandatory to confirm genetic results, we analyzed the T-381C polymorphism in seven independent case-control cohorts and in 291 T2D-enriched pedigrees totalling 39 557 subjects of European origin. A meta-analysis of the seven case-control studies (n = 39 040) showed a nominal protective effect [odds ratio (OR) = 0.86 (0.79-0.94), P = 0.0006] of the CC genotype on T2D risk, consistent with the previous study. By combining all available data (n = 49 279), we further confirmed a modest contribution of the BNP T-381C polymorphism for protection against T2D [OR = 0.86 (0.80-0.92), P = 1.4 x 10(-5)]. Potential confounders such as gender, age, obesity status or family history were tested in 4335 T2D and 4179 normoglycemic subjects and they had no influence on T2D risk. This study provides further evidence of a modest contribution of the BNP T-381C polymorphism in protection against T2D and illustrates the difficulty of unambiguously proving modest-sized associations even with large sample sizes.

Surgical Prevention of Weight Regain and Type 2 Diabetes Recurrence in 3 Different Bariatric Operations and Their Differential Long-Term Outcome: An 8-Year Prospective Observational Study.

Introduction: Comparative data on long-term outcomes of mechanistically different bariatric operations are scarce. Methods: In this prospective, observational study, consecutive patients with severe obesity were studied using a predefined reoperation algorithm to determine long-term health outcomes after bariatric surgery (BS): adjustable gastric banding (AGB), Roux-en-Y gastric bypass (RYGB), or biliopancreatic diversion (BPD). All patients were assessed for mortality, postoperative weight loss, rate of reoperation, comorbidities, and quality of life (QoL) 8 years after surgery. Results: Between 1996 and 2008, 2364 Swiss patients, with a mean body mass index of 43 ± 7 kg/m2 (mean ± SD) underwent AGB (n = 1404), RYGB (n = 790), or BPD (n = 170). Two thousand two hundred twenty-eight (94%) were followed for 8 years after BS. Eight-year mortality of the whole study group was 34.3 per 104 person-years. Percent excessive weight loss at 8 years was 56.7 ± 1.4% (95% confidence interval) in AGB, 62.5 ± 2.4% in RYGB and 64.8+-3.0% in BPD. The rate of major reoperation was highest in AGB and significantly lower in RYGB and BPD (63.4 vs 54.3 vs 47.2 per 103 person-years, P < 0.001). Remission of comorbidities was observed across all 3 groups, with key improvement (P < 0.01) in esophagitis in the RYGB group, and type 2 diabetes (T2D) (>60%) in procedures involving duodenal exclusion. Total improvement in QoL was similar between the 3 types of operations but was strongly correlated with weight loss preservation (P < 0.001). Conclusions: BS, at the expense of a high reoperation rate but low procedural mortality, considerably improves the QoL and results in sustained remission of comorbidities, especially T2D using a predefined reoperation algorithm developed to prevent weight regain and operation-specific complications.

Reversal of Long-Term Weight Regain After Roux-en-Y Gastric Bypass Using Liraglutide or Surgical Revision. A Prospective Study.

PURPOSE: This study investigates whether pharmacotherapy with liraglutide is similarly effective in reversing weight regain more than 6 years after Roux-en-Y gastric bypass (RYGB) as revisional surgery aimed at restoring restriction. METHODS: Ninety-five consecutive patients (11 male, 84 female; mean BMI 45 ± 6 kg/m2) undergoing RYGB 9 ± 4 years ago were treated for 24 months as follows: Patients, who gained less than 10% from weight NADIR, served as controls and were provided lifestyle counseling (DC, n = 30). The others were allowed to choose between three different treatment groups: daily s.c. administration of liraglutide (LG, n = 34); endosurgery using Apollo's Overstitch System™ (ES, n = 15), or implantation of a Fobi-ring with pouch resizing (FP, n = 16). RESULTS: Controls kept their weight stable during 24 months of study (- 0.1 ± 1.7 kg/m2). Weight loss was 4.8 ± 2.9 kg/m2 for LG and 5.5 ± 2.9 kg/m2 for FP, both losing more than 85% of regained weight from weight NADIR (p < 0.001). In contrast, weight loss in ES was 1.0 ± 0.9 kg/m2 (i.e., 20% of regained weight). Thirty-seven percent of FP experienced serious complications (p < 0.05) in contrast to the other groups. An improved prevalence of hypertension and dyslipidemia was observed in LG and FP (p < 0.02) 24 months after intervention. CONCLUSIONS: Weight regain during more than 6 years after RYGB can be safely and effectively reversed with liraglutide. Compared with revisional surgery, pharmacotherapy with liraglutide was low risk and resulted in an important improvement in hypertension and dyslipidemia. Therefore, daily subcutaneous injections of liraglutide are a valid option to treat weight regain after RYGB.

Endocannabinoid receptor 1 gene variations increase risk for obesity and modulate body mass index in European populations.

The therapeutic effects of cannabinoid receptor blockade on obesity-associated phenotypes underline the importance of the endocannabinoid pathway on the energy balance. Using a staged-approach, we examined the contribution of the endocannabinoid receptor 1 gene (CNR1) on obesity and body mass index (BMI) in the European population. With the input of CNR1 exons and 3' and 5' regions sequencing and HapMap database, we selected and genotyped 26 tagging single-nucleotide polymorphisms (SNPs) in 1932 obese cases and 1173 non-obese controls of French European origin. Variants that showed significant associations (P < 0.05) with obesity after correction for multiple testing were further tested in two additional European cohorts including 2645 individuals. For the identification of the potential causal variant(s), we further genotyped SNPs in high linkage disequilibrium (LD) with the obesity-associated variants. Of the 25 successfully genotyped CNR1 SNPs, 12 showed nominal evidence of association with childhood obesity, class I and II and/or class III adult obesity (1.16 < OR < 1.40, 0.00003 < P < 0.04). Intronic SNPs rs806381 and rs2023239, which resisted correction for multiple testing were further associated with higher BMI in both Swiss obese subjects and Danish individuals. The genotyping of all know variants in partial LD (r(2) > 0.5) with these two SNPs in the initial case-control study, identified two better associated SNPs (rs6454674 and rs10485170). Our study of 5750 subjects shows that CNR1 variations increase the risk for obesity and modulate BMI in our European population. As CB1 is a drug target for obesity, a pharmacogenetic analysis of the endocannabinoid blockade obesity treatment may be of interest to identify best responders.

Successful multi-intervention treatment of severe obesity: a 7-year prospective study with 96% follow-up.

BACKGROUND: No long-term, high participation study of the outcome of bariatric surgery has examined how a multi-intervention approach to the treatment of severe obesity can achieve and sustain weight loss after an initial bariatric procedure. METHODS: We employed a multi-intervention treatment that combines adjustable gastric banding with intensive follow-up to support patient life-style change and use of an algorithm allowing reoperation-to bypass, if necessary-in the event of complications. Four hundred four severely obese patients with an average BMI = 42.6 at the outset had initial AGB surgery and were followed with a high rate of face-to-face consultations for 7 years. Seventy-five percent of the patients retained a gastric band throughout the study. Weight loss, complications, and comorbidities were studied, and quality of life was assessed using Bariatric Analysis and Reporting Outcome System (BAROS). RESULTS: Three hundred eighty-eight (96%) patients completed the 7-year follow-up. Average BMI reduction at 5 years was 28% and remained stable through year 7, at which the mean excess weight loss was 61%. The preoperative prevalence of metabolic syndrome, 59.7%, decreased to 13.3% at 7 years and was abolished for patients with more than 40% loss of initial BMI. Similar changes were seen for all components of metabolic syndrome. More than 60% of patients had a "good" or higher BAROS score; 10.1% were considered failures. Patients converted to gastric bypass, and those retaining gastric bands throughout the study had very similar outcomes. CONCLUSIONS: Long-term, multi-intervention treatment of severe obesity can achieve and preserve weight loss and thus improved quality of life and sustained reduction or disappearance of all components of metabolic syndrome, for a high proportion of severely obese patients with preoperative BMI between 35 and 55.

The genetic susceptibility to type 2 diabetes may be modulated by obesity status: implications for association studies.

BACKGROUND: Considering that a portion of the heterogeneity amongst previous replication studies may be due to a variable proportion of obese subjects in case-control designs, we assessed the association of genetic variants with type 2 diabetes (T2D) in large groups of obese and non-obese subjects. METHODS: We genotyped RETN, KCNJ11, HNF4A, HNF1A, GCK, SLC30A8, ENPP1, ADIPOQ, PPARG, and TCF7L2 polymorphisms in 1,283 normoglycemic (NG) and 1,581 T2D obese individuals as well as in 3,189 NG and 1,244 T2D non-obese subjects of European descent, allowing us to examine T2D risk over a wide range of BMI. RESULTS: Amongst non-obese individuals, we observed significant T2D associations with HNF1A I27L [odds ratio (OR) = 1.14, P = 0.04], GCK -30G>A (OR = 1.23, P = 0.01), SLC30A8 R325W (OR = 0.87, P = 0.04), and TCF7L2 rs7903146 (OR = 1.89, P = 4.5 x 10-23), and non-significant associations with PPARG Pro12Ala (OR = 0.85, P = 0.14), ADIPOQ -11,377C>G (OR = 1.00, P = 0.97) and ENPP1 K121Q (OR = 0.99, P = 0.94). In obese subjects, associations with T2D were detected with PPARG Pro12Ala (OR = 0.73, P = 0.004), ADIPOQ -11,377C>G (OR = 1.26, P = 0.02), ENPP1 K121Q (OR = 1.30, P = 0.003) and TCF7L2 rs7903146 (OR = 1.30, P = 1.1 x 10-4), and non-significant associations with HNF1A I27L (OR = 0.96, P = 0.53), GCK -30G>A (OR = 1.15, P = 0.12) and SLC30A8 R325W (OR = 0.95, P = 0.44). However, a genotypic heterogeneity was only found for TCF7L2 rs7903146 (P = 3.2 x 10-5) and ENPP1 K121Q (P = 0.02). No association with T2D was found for KCNJ11, RETN, and HNF4A polymorphisms in non-obese or in obese individuals. CONCLUSION: Genetic variants modulating insulin action may have an increased effect on T2D susceptibility in the presence of obesity, whereas genetic variants acting on insulin secretion may have a greater impact on T2D susceptibility in non-obese individuals.

Bowel habits after bariatric surgery.

BACKGROUND: Disordered bowel habits might influence quality of life after bariatric surgery. Different types of bariatric operations-gastric banding (AGB), Roux-en-Y gastric bypass (RYGB), or biliopancreatic diversion (BPD)-might alter bowel habits as a consequence of the surgical procedure used. Whether change in bowel habits affects quality of life after AGB, RYGB, or BPD differently is unknown. METHODS: The study group contained 290 severely obese patients undergoing bariatric surgery between August 1996 and September 2004 [BPD: n = 103, 64.1% women, age 43 +/- 1 years (mean +/- SEM), BMI 53.9 +/- 0.9 kg/m(2), weight 153.4 +/- 2.9 kg; Roux-en-Y gastric bypass: n = 126, 73.0% women, age 43 +/- 1 years, BMI 44.2 +/- 0.3 kg/m(2), weight 123.8 +/- 1.5 kg; adjustable gastric banding (AGB): n = 61, 57.4% women, age 44 +/- 1 years, BMI 49.9 +/- 0.5 kg/m(2), weight 146.1 +/- 2.0 kg). Changes in bowel habits, flatulence, flatus odor, and effects on social life were estimated at least 4 months after surgery using a self-administered questionnaire. RESULTS: Fecal consistency changed significantly after surgery. Loose stools and diarrhea were more frequent after BPD and RYGB (P < 0.001) but more so after BPD than after either RYGB or AGB (P < 0.002). Constipation was more likely after AGB (P = 0.03). In addition, malodorous flatus affecting social life was more frequent after BPD than after either RYGB or AGB (P < 0.003). Furthermore, flatus frequency increased after BPD and RYGB, and patients were more bothered by their malodorous flatus than after AGB (all P < 0.001). Flatus severity score was highest in BPD, intermediate in RYGB, and lowest in AGB patients (all P < 0.001), a difference that was not influenced by frequency of metabolic syndrome before and after surgery. Moreover, observation period after surgery had no influence on overall results of bowel habits. Subsore quality of life bariatric analysis and reporting outcome system (BAROS) scores were largely similar between all three groups. However, flatulence severity score correlated inversely with quality of life estimated by BAROS in BPD and RYGB, but not in AGB patients. CONCLUSIONS: The type of bariatric surgery affects bowel habits in an operation-specific manner, resulting mainly in diarrhea after BPD and RYGB, and constipation after AGB. Flatulence severity impairs quality of life most in BPD, is intermediate in RYGB, and is only minor after AGB, a phenomenon that was only partially mirrored in quality-of-life measures of BAROS.

Severe recurrent hypoglycemia after gastric bypass surgery.

BACKGROUND: Bariatric surgery is, at present, the most effective method to achieve major, long-term weight loss in severely obese patients. Recently, severe recurrent symptomatic hyperinsulinemic hypoglycemia was described as a consequence of gastric bypass surgery (GBS) in a small series of patients with severe obesity. Pancreatic nesidioblastosis, a hyperplasia of islet cells, was postulated to be the cause, and subtotal or total pancreatectomy was the suggested treatment. METHODS: We observed that severe, disabling hypoglycemia after GBS occurred only in patients with loss of restriction. Whether restoration of gastric restriction might treat severe, recurrent hypoglycemia after GBS is unknown. RESULTS: Therefore, gastric restriction was restored by surgical placement of a silastic ring (n = 8, first two patients with additional distal pancreatectomy) or an adjustable gastric band (n = 4) around the pouch in 12 consecutive patients presenting with severe hypoglycemia (blood glucose below 2.2 mM). At follow-up after restoration of gastric restriction (median follow-up 7 months, range 5 to 19 months), 11 patients demonstrated no hypoglycemic episodes, while one had recurrence of hypoglycemia and underwent distal pancreatectomy. Procedural mortality was 0% and morbidity 8.3%. CONCLUSION: Patients suffering from severe recurrent hypoglycemia after GBS can be treated, in most cases, just by restoration of gastric restriction. Distal pancreatectomy should be considered a second-line treatment.

Binge eating as a major phenotype of melanocortin 4 receptor gene mutations.

BACKGROUND: Obesity, a multifactorial disease caused by the interaction of genetic factors with the environment, is largely polygenic. A few mutations in these genes, such as in the leptin receptor (LEPR) gene and melanocortin 4 receptor (MC4R) gene, have been identified as causes of monogenic obesity. METHODS: We sequenced the complete MC4R coding region, the region of the proopiomelanocortin gene (POMC) encoding the alpha melanocyte-stimulating hormone, and the leptin-binding domain of LEPR in 469 severely obese white subjects (370 women and 99 men; mean [+/-SE] age, 41.0+/-0.5 years; body-mass index [the weight in kilograms divided by the square of the height in meters], 44.1+/-2.0). Fifteen women and 10 men without a history of dieting or a family history of obesity served as normal-weight controls (age, 47.7+/-2.0 years; body-mass index, 21.6+/-0.4). Detailed phenotypic data, including information on body fat, resting energy expenditure, diet-induced thermogenesis, serum concentrations of leptin, and eating behavior, were collected. RESULTS: Twenty-four obese subjects (5.1 percent) and one control subject (4 percent) had MC4R mutations, including five novel variants. Twenty of the 24 obese subjects with an MC4R mutation were matched for age, sex, and body-mass index with 120 of the 445 obese subjects without an MC4R mutation. All mutation carriers reported binge eating, as compared with 14.2 percent of obese subjects without mutations (P<0.001) and 0 percent of the normal-weight subjects without mutations. The prevalence of binge eating was similar among carriers of mutations in the leptin-binding domain of LEPR and noncarriers. No mutations were found in the region of POMC encoding alpha melanocyte-stimulating hormone. CONCLUSIONS: Binge eating is a major phenotypic characteristic of subjects with a mutation in MC4R, a candidate gene for the control of eating behavior.

Eating Behavior, Low-Frequency Functional Mutations in the Melanocortin-4 Receptor (MC4R) Gene, and Outcomes of Bariatric Operations: A 6-Year Prospective Study.

OBJECTIVE: Data on the effects of eating behavior and genetics on outcomes of gastrointestinal surgery for diabesity have been sparse, often flawed, and controversial. We aimed to assess long-term outcomes of bariatric operations in patients characterized for eating behavior and rare mutations in the melanocortin-4 receptor (MC4R) gene, which is strongly implicated in energy balance. RESEARCH DESIGN AND METHODS: Between 1996 and 2005, 1,264 severely obese Swiss patients underwent current laparoscopic adjustable gastric banding, gastroduodenal bypass, or a hybrid operation. Of these, 872 patients were followed for a minimum of 6 years and were screened for MC4R mutations. Using regression models, we studied relationships between eating behavior and MC4R mutations and postoperative weight loss, complications, and reoperations after 6 years. RESULTS: At baseline, rare functional MC4R mutation carriers exhibited a significantly higher prevalence of binge eating disorder (BED) or loss-of-control eating independent of age, sex, and BMI. Six years after bariatric surgery, the mutation carriers had more major complications than wild-type subjects independent of age, baseline BMI, sex, operation type, and weight loss. Furthermore, high baseline BMI, male sex, BED, and functional MC4R mutations were independent predictors of higher reoperation rates. CONCLUSIONS: Sequencing of MC4R and eating typology, combined with stratification for sex and baseline BMI, might significantly improve patient allocation to banding or bypass operations for diabesity as well as reduce both complication and reoperation rates.

Health-related quality of life in patients with class II and class III obesity.

BACKGROUND: Severe obesity may substantially impact quality of life. We estimated the health-related quality of life (HRQoL) in patients with class II and class III obesity, and explored the impact of patient characteristics and co-morbidities on quality of life. METHODS: 110 patients with BMI > or = 35 kg/m2 presenting for evaluation for bariatric surgery were asked to complete the EuroQoL questionnaire. Co-morbidities of the patients were recorded, including coxarthralgia, gonarthralgia, foot problems (pain and arthrosis), diabetes, dyslipidemia, hypertension, infertility, coronary heart disease, low back pain, peptic esophagitis, sleep apnea syndrome, urinary stress incontinence, and venous insufficiency. The determinants of HRQoL on the EQ-VAS score and EQ-5D index (both ranging from 0-100) were analyzed in a univariate and multivariate linear regression model. RESULTS: The mean EQ-5D index (societal perspective) was 76, whereas the mean EQ-VAS (patient perspective) was 66 (P<0.0001). The mean number of comorbidities was 4.9 (range 0-11). Dyslipidemia (68%), low back pain (63%) and venous insufficiency (57%) were the 3 most frequent co-morbidities. However, low back pain (beta= -11.4) and foot problems (beta= -8.5) were significantly associated with a reduction in the EQ-VAS score, whereas low back pain (beta= -8.4) and coronary heart disease (beta= -24.9) were significantly associated with a reduction in the EQ-5D index. CONCLUSION: The number and type of co-morbidities determine HRQoL in patients with severe obesity. Within our study population, a higher BMI, however, was not associated with a lower quality of life.

Salvage of gastric restriction following staple-line dehiscence after vertical banded gastroplasty by insertion of an adjustable gastric band.

BACKGROUND: Vertical banded gastroplasty (VBG) has been a common and safe surgical treatment for morbid obesity. However, the complication of staple-line dehiscence (SLD) results in VBG failure. We present a minimally invasive revision procedure when SLD occurs: gastric restriction is salvaged by adjustable gastric banding (AGB), usually laparoscopically, providing that the previous restriction had achieved sufficient weight loss initially and was well-tolerated. METHODS: 13 patients with unexplained weight regain after VBG were found to have SLD on endoscopy. AGB was performed to re-establish restriction. Weight loss and complications were compared with two control groups: the first undergoing uncomplicated VBG, and the second undergoing AGB alone. Follow-up of 4.3+/-0.1 (mean+/-SEM) years after salvage reoperation, including complications, reoperations and weight loss, were studied. RESULTS: Insertion of the band through the retrogastric tunnel was feasible in all cases, despite adhesions in the area of the VBG Marlex band, the proximal stomach, and left lobe of liver. There was no surgeryrelated mortality. Following "salvage AGB", weight loss and overall complication rates were similar between the study group and the two control groups. CONCLUSION: Salvage of gastric restriction by AGB after SLD secondary to VBG is safe and reliable, despite the possibility of adhesions. Morbidity is low and intermediate-term weight loss is comparable to patients with uncomplicated VBG.

Impact of age, sex and body mass index on outcomes at four years after gastric banding.

BACKGROUND: Adjustable gastric banding for weight reduction in severely obese persons allows reversible individualized restriction during postoperative follow-up. It is unknown whether preoperative age, sex and BMI might modulate treatment outcome. METHODS: 404 severely obese patients (79% women; age 42 +/- 0.5 years [mean +/- SEM]; BMI 42.1 +/- 0.2 kg/m2) completed 4-year follow-up after banding. Weight loss, complications, and Bariatric Analysis and Reporting Outcome System (BAROS) scores were recorded prospectively. RESULTS: 4 years after banding, younger (<50 years) women lost more weight than older (50 years) men (28.2 +/- 0.7% vs 19.4+/- 1.6%; P=0.001); older women and younger men lost similar weight. Patients with preoperative BMI >50 lost more weight than patients with BMI <35 (30.5 +/- 2.3% vs 22.8 +/- 2.6%; P=0.03). 22.3% of patients (n=90) had band system-related complications. Compared to women, men had more band leaks (7.0% vs 1.9%; P=0.007), and older men had more band slippages than younger men (8.4% vs 0.0%; P=0.035). Patients with preoperative BMI >50 were less likely than patients with BMI 35-40 or 40-50 to experience gastric complications (10.6%, 18.8%, 23.0%, respectively), but more likely to experience port/tube complications (15.8%, 2.4%, 7.9%, respectively; P<0.055). BAROS scores were different between men and women (P=0.05), and between younger and older people (P=0.001). Women and younger people were more likely than men and older people to score "very good" (P=0.03, P=0.001, respectively). CONCLUSIONS: Adjustable gastric banding is an effective intermediate-term treatment for severe obesity. Preoperative age, sex, and BMI are important modulators of outcome and should be considered during preoperative evaluation.

Management of failed adjustable gastric banding.

BACKGROUND: About 100,000 adjustable gastric band placements have been performed worldwide, but more than 10% of patients have needed reoperation for insufficient weight loss or device-related complications. This study investigates the complications following gastric banding, and the outcome using a structured management strategy. METHODS: In the period April 1996 to January 2002, 824 severely obese patients (body mass index 43 +/- 1 kg/m 2 [mean +/- standard error under the mean], age 43 +/- 1 years; 77% women) underwent gastric banding in a single institution and were followed prospectively. Complications, insufficient weight loss, and subsequent management were analyzed. RESULTS: By the fifth treatment year, excess weight loss (EWL) was 54.8 +/- 1.7%; 72.8% of patients lost weight continuously or attained EWL of at least 50%. Insufficient weight loss occurred in 143 patients, and band-related complications occurred in 131 patients, with a mean annual rate of 5.0%. Major reoperation was necessary in 121 patients, and the annual reoperation rate was 4.7%. Following major reoperation, band- and bypass-related complication rates ranged from 6.3% to 11.7% per year. Three deaths occurred, 1 after reoperation and 2 due to preexisting cardiovascular disease. CONCLUSIONS: Applying a structured reoperation algorithm, 5% annual failure after banding was corrected in most patients, and 72.8% of patients attained sufficient weight loss. Reoperation-related mortality was low (.8%), and its annual morbidity was acceptable (4.6%).

Analysis of sequence variability in the CART gene in relation to obesity in a Caucasian population.

BACKGROUND: Cocaine and amphetamine regulated transcript (CART) is an anorectic neuropeptide located principally in hypothalamus. CART has been shown to be involved in control of feeding behavior, but a direct relationship with obesity has not been established. The aim of this study was to evaluate the effect of polymorphisms within the CART gene with regards to a possible association with obesity in a Caucasian population. RESULTS: Screening of the entire gene as well as a 3.7 kb region of 5' upstream sequence revealed 31 SNPs and 3 rare variants; 14 of which were subsequently genotyped in 292 French morbidly obese subjects and 368 controls. Haplotype analysis suggested an association with obesity which was found to be mainly due to SNP-3608T>C (rs7379701) (p = 0.009). Genotyping additional cases and controls also of European Caucasian origin supported further this possible association between the CART SNP -3608T>C T allele and obesity (global p-value = 0.0005). Functional studies also suggested that the SNP -3608T>C could modulate nuclear protein binding. CONCLUSION: CART SNP -3608T>C may possibly contribute to the genetic risk for obesity in the Caucasian population. However confirmation of the importance of the role of the CART gene in energy homeostasis and obesity will require investigation and replication in further populations.

Laparoscopic adjustable gastric banding with duodenal switch for morbid obesity: technique and preliminary results.

BACKGROUND: The procedure of choice for morbid obesity remains controversial. One of the most effective treatments is the biliopancreatic diversion with duodenal switch (BPD/DS), which is, however, associated with a significant morbidity rate. Adjustable gastric banding (AGB) by the laparoscopic approach is an easier procedure with the intent to reduce complication rates. It replaced the sleeve gastrectomy in this study. The objective was to assess the feasibility and safety of this new laparoscopic treatment. METHODS: AGB with duodenal switch (DS) was performed laparoscopically with 7 trocars. A gastric band was appropriately placed below the gastroesophageal junction, followed by BPD/DS with a 250-cm alimentary channel and a 100-cm common channel. RESULTS: All 5 patients were women, with mean preoperative BMI 52.2 kg/m(2) (40.6 to 64.4). The operations were performed via laparoscopy in a mean of 206 +/- 35 minutes. There was no postoperative complication, infection or conversion. Mean hospital stay was 8.8 days (8-11). At 12 months, mean BMI is 35.8 kg/m(2) (26.1-46.0), with continuing weight loss and no hypoalbuminemia. CONCLUSIONS: These data suggest that laparoscopic AGB/DS is feasible, with a low morbidity rate. This technique could combine the long-term weight loss of malabsorptive procedures, with a low-morbidity, adjustable, restrictive procedure. This technique could be used in selected patients, but requires a larger study with longer follow-up.

Impact of orlistat therapy on weight reduction in morbidly obese patients after implantation of the Swedish adjustable gastric band.

BACKGROUND: Adjustable gastric banding (AGB) is frequently performed to treat morbid obesity. One problem which can occasionally develop after a restrictive procedure is consumption of a high calorie liquid diet, which may prohibit further weight loss. Orlistat, a newly developed intestinal lipase inhibitor, prevents absorption of about one-third of ingested fat. It is unknown whether patients no longer losing weight after AGB, despite further band restriction, may lose weight with addition of orlistat. METHODS: 38 patients were selected who had stopped losing weight 3 months before the initiation of the study, 18 +/- 6 months (mean +/- SEM) after laparoscopic AGB. Subjects were divided into 2 groups, matched for age, sex, filling volume of the band and body mass index (BMI) both at the time of surgery and start of the study (18 +/- 6 months after AGB). RESULTS: Patients in group A received dietary counseling and orlistat 120 mg TID for 8 months, while patients in group B received only dietary counseling. During the following 8 months of study, subjects in group A lost 8 +/- 3 kg in weight, whereas subjects in group B lost 3 +/- 2 kg (p < 0.01, months 18 vs 26 of study; p < 0.03, group A vs B). In 15 patients from group A the study was further extended 9 months, but interestingly, weight remained stable independent of whether orlistat was continued (n = 8) or stopped (n = 7). 4 subjects were excluded from the extension study because of additional malabsorptive bypass surgery. Subjects taking orlistat encountered only minor GI side-effects. CONCLUSION: Orlistat appears to be useful when added in patients after AGB who are no longer losing weight, perhaps due to a high-calorie liquid diet rich in fat.