Long-term Treatment Of Obesity Research Articles

Influence of fatty acid synthase inhibitor orlistat on the DNA repair enzyme O6-methylguanine-DNA methyltransferase in human normal or malignant cells in vitro.

Tetrahydrolipstatin (orlistat), an inhibitor of lipases and fatty acid synthase, is used orally for long-term treatment of obesity. Although the drug possesses striking antitumor activities in vitro against human cancer cells and in vitro and in vivo against animal tumors, it also induces precancerous lesions in rat colon. Therefore, we tested the in vitro effect of orlistat on the expression of O6-methylguanine-DNA methyltransferase (MGMT), a DNA repair enzyme that plays an essential role in the control of mutagenesis and carcinogenesis. Western blot analysis demonstrated that 2-day continuous exposure to 40 µM orlistat did not affect MGMT levels in a human melanoma cell line, but downregulated the repair protein by 30-70% in human peripheral blood mononuclear cells, in two leukemia and two colon cancer cell lines. On the other hand, orlistat did not alter noticeably MGMT mRNA expression. Differently from lomeguatrib (a false substrate, strong inhibitor of MGMT) orlistat did not reduce substantially MGMT function after 2-h exposure of target cells to the agent, suggesting that this drug is not a competitive inhibitor of the repair protein. Combined treatment with orlistat and lomeguatrib showed additive reduction of MGMT levels. More importantly, orlistat-mediated downregulation of MGMT protein expression was markedly amplified when the drug was combined with a DNA methylating agent endowed with carcinogenic properties such as temozolomide. In conclusion, even if orlistat is scarcely absorbed by oral route, it is possible that this drug could reduce local MGMT-mediated protection against DNA damage provoked by DNA methylating compounds on gastrointestinal tract epithelial cells, thus favoring chemical carcinogenesis.

New targets to treat obesity and the metabolic syndrome

Metabolic syndrome (MetS) is a cluster ofassociated metabolic traits that collectively confer unsurpassed risk for development of cardiovascular disease (CVD) and type 2 diabetes compared to any single CVD risk factor. Truncal obesity plays an exceptionally critical role among all metabolic traits of the MetS. Consequently, the prevalence of the MetS has steadily increased with the growing epidemic of obesity. Pharmacotherapy has been available for obesity for more than one decade, but with little success in improving the metabolic profiles.The serotonergic drugs and inhibitors of pancreatic lipases were among the few drugs that were initially approved to treat obesity. At the present time, only the pancreatic lipase inhibitor orlistat is approved for long-term treatment of obesity. New classes of anti-diabetic drugs, including glucagon-like peptide 1 receptor (GLP-1R) agonists and Dipeptidyl-peptidase IV (DPP-IV) inhibitors, are currently being evaluated for their effects on obesity and metabolic traits. The genetic studies of obesity and metabolic syndrome have identified novel molecules acting on the hunger and satiety peptidergic signaling of the gut-hypothalamus axis or the melanocortin system of the brain and are promising targets for future drug development. The goal is to develop drugs that not only treat obesity, but also favorably impact its associated traits.

Pharmacological approaches to the management of binge eating disorder.

In the USA, binge eating disorder (BED) is the most common eating disorder, with a lifetime prevalence of ~3.5% in adult women, 2.0% in adult men, and 1.6% in adolescents. BED is characterized by frequent episodes of binge eating that are accompanied by a sense of loss of control over eating and result in marked psychological distress. BED is highly co-morbid with obesity and with depression and other psychiatric conditions, and it is associated with substantial role impairment. Currently, there are no US FDA-approved pharmacological treatments for BED. Animal and human studies implicate underlying dysregulation in dopamine, opioid, acetylcholine, and serotonin neurocircuitry within brain reward regions in the pathogenesis and maintenance of BED. To date, the efficacy of various agents that target these and other neurotransmitter systems involved in motivated feeding behavior, mood regulation, and impulse control have been investigated in the treatment of BED. Several antidepressant and anticonvulsant agents have demonstrated efficacy in reducing binge eating frequency, but only in limited cases have these effects resulted in patients achieving abstinence, which is the primary goal of treatment; they also range from less (fluvoxamine) to more (topiramate) effective in achieving weight loss that is both clinically meaningful and significantly greater than placebo. Collectively, the literature on pharmacological treatment approaches to BED is limited in that very few agents have been studied in multiple, confirmatory trials with adequate follow up, and almost none have been evaluated in large patient samples that are diverse with respect to age, sex, and ethnicity. In addition, prior trials have not adequately addressed, through study design, the high placebo response commonly observed in this patient population. Several novel agents are in various phases of testing, and recent animal studies focusing on glutamate-signaling circuits linking the amygdala to the lateral hypothalamus offer new avenues for exploration and potential therapeutic development. Studies of newly FDA-approved medications for long-term obesity treatment and further explorations of dietary supplements and neutraceuticals with appetite- and mood-altering properties may also be worthwhile.

Tolerability and safety of the new anti-obesity medications.

Worldwide obesity prevalence has nearly doubled since 1980. Due to numerous co-morbidities, obesity represents a serious health and socioeconomic problem worldwide. Pharmacotherapy should be an integral part of comprehensive obesity management. Drug therapy can assist in weight loss and its maintenance in those individuals who do not achieve appropriate weight loss through lifestyle interventions alone. After the withdrawal of sibutramine from the market in 2010, orlistat, a lipase inhibitor, was the only remaining prescription drug approved for the long-term treatment of obesity. In 2012, phentermine/topiramate extended-release (PHEN/TPMER) combination and lorcaserin were approved by the US FDA as novel medications for long-term weight management. Three major phaseIII trials conducted with each drug confirmed their efficacy in terms of weight loss/maintenance and improvement of cardiometabolic risks. No head-to-head studies between the two new anti-obesity drugs have been carried out. However, in the existing studies PHEN/TPMER had a superior weight loss profile to lorcaserin but the incidence of adverse effects was lower with lorcaserin. Both drugs were well-tolerated, and adverse events were modest in intensity, dose dependent, rather rare, and tended to decrease with the duration of treatment. Major safety concerns regarding PHEN/TPMER include elevations in resting pulse rate, teratogenicity, mild metabolic acidosis, and psychiatric and cognitive adverse events. Valvulopathy, cognitive impairment, psychiatric disorders, and hypoglycemia represent major safety concerns for lorcaserin. Although existing trials have not demonstrated any significant issues with PHEN/TPMER-induced heart rate elevation and lorcaserin-induced valvulopathy, all safety concerns should be seriously taken into account in patients treated with either of these novel anti-obesity medications.

Cost-Effectiveness Analysis of Qsymia for Weight Loss.

BackgroundPhase 3 clinical trial results reveal that Qsymia is a clinically effective long-term treatment for obesity, but whether this treatment is cost-effective compared to a diet and lifestyle intervention has yet to be explored.ObjectiveTo quantify the incremental cost-effectiveness of Qsymia (phentermine and topiramate extended-release) for health-related quality of life improvements.Study design and methodsEstimates are based on cost and quality of life outcomes from a 56-week, multicenter, placebo-controlled, phase 3 clinical trial undertaken in 93 health centers in the US. Participants were overweight and obese adults (aged 18–70 years) with a body-mass index of 27–45 kg/m2 and two or more comorbidities (hypertension, dyslipidemia, diabetes or pre-diabetes or abdominal obesity). The intervention was diet and lifestyle advice plus the recommended dose of Qsymia (phentermine 7.5 mg plus topiramate 46.0 mg) vs. control, which included diet and lifestyle advice plus placebo. The study was from the payer perspective. Costs included the prescription cost, medication cost offsets and physician appointment costs. Effectiveness was measured in terms of quality-adjusted life years gained (QALYs). The main outcome measure was incremental cost per QALY gained of the intervention relative to control.ResultsOur base-case model, in which participants take Qsymia for 1 year with benefits linearly decaying over the subsequent 2 years, generates an incremental cost-effectiveness ratio (ICER) of $48,340 per QALY gained. Using the base-case assumptions, probabilistic sensitivity analyses reveal that the ICER is below $50,000 per QALY in 54 % of simulations. However, results are highly dependent on the extent to which benefits are maintained post medication cessation. If benefits persist for only 1 year post cessation, the ICER increases to $74,480.ConclusionAlthough base-case results suggest that Qsymia is cost-effective, this result hinges on the time on Qsymia and the extent to which benefits are maintained post medication cessation. This should be an area of future research.Electronic supplementary materialThe online version of this article (doi:10.1007/s40273-014-0182-6) contains supplementary material, which is available to authorized users.

Enhanced gastric tolerability and improved anti-obesity effect of capsaicinoids-loaded PCL microparticles

Capsaicinoids show several pharmacological effects including weight loss. However, their pungency limits the long-term use through the gastrointestinal tract. In that sense, the goal of this study was to prepare capsaicinoids-loaded poly(ε-caprolactone) microparticles as an oral carrier in order to improve their gastric tolerability and to make feasible the long-term treatment of obesity. Formulations containing 3, 5 and 10% capsaicinoids were successfully obtained by simple emulsion/solvent evaporation method. Values of encapsulation efficiency above 90% were achieved. Microparticles showed spherical shape and smooth surface. The particle size was suitable for oral use in order to provide an extended release through the gastrointestinal tract. No chemical bond was observed between drug and polymer. Microencapsulation led to drug amorphization. Formulations prolonged the release of capsaicinoids without changing the release kinetic (biexponential model). Microencapsulation increased the gastric tolerability of capsaicinoids because it prevented inflammatory processes in the stomach of rats. Microparticles containing 5% capsaicinoids demonstrated a statistically significant reduction of Lee index, mesenteric and retroperitoneal fat pads of rats with obesity induced by hypothalamic lesion using monosodium l-glutamate. In summary, capsaicinoids-loaded poly(ε-caprolactone) microparticles are low-irritative oral controlled-release carriers for a long-term use in obesity.

Update on obesity pharmacotherapy

There are two groups of approved drugs that can be used to manage weight in patients with obesity: medications approved for obesity per se and medications that affect body weight for obese patients who have complications from their obesity and are receiving these medications for chronic disease management. For obesity per se, treatment is with one of the three drugs currently approved for long-term treatment of obesity or one of a few others that can be used for short-term treatment. Among these, orlistat partially blocks intestinal digestion of fat and produces weight loss of 5-8 kg but major limitations are associated gastrointestinal symptoms; lorcaserin, a serotonin-2C agonist with few side effects, produces a mean weight loss of 4-7 kg; and the combination of phentermine and topiramate (extended release) produces a mean weight loss of 8-10 kg, but should only be used after verifying a woman is not pregnant. Failure to lose more than 3% of body weight within 3 months with any of these agents should lead to reevaluation of therapy. The short-term drugs for treating obesity per se are sympathomimetics, with phentermine being most widely used. The second group of drugs is for weight-centric prescribing for patients with a chronic disease such as diabetes, depression, or psychiatric disorders. For each disorder, some drugs produce weight gain, others are weight neutral, but the best choice for these patients is the combination of drugs that treat the underlying condition and also produce weight loss.

Long-term drug treatment for obesity: a systematic and clinical review.

Thirty-six percent of US adults are obese, and many cannot lose sufficient weight to improve health with lifestyle interventions alone. To conduct a systematic review of medications currently approved in the United States for obesity treatment in adults. We also discuss off-label use of medications studied for obesity and provide considerations for obesity medication use in clinical practice. A PubMed search from inception through September 2013 was performed to find meta-analyses, systematic reviews, and randomized, placebo-controlled trials for currently approved obesity medications lasting at least 1 year that had a primary or secondary outcome of body weight change, included at least 50 participants per group, reported at least 50% retention, and reported results on an intention-to-treat basis. Studies of medications approved for other purposes but tested for obesity treatment were also reviewed. Obesity medications approved for long-term use, when prescribed with lifestyle interventions, produce additional weight loss relative to placebo ranging from approximately 3% of initial weight for orlistat and lorcaserin to 9% for top-dose (15/92 mg) phentermine plus topiramate-extended release at 1 year. The proportion of patients achieving clinically meaningful (at least 5%) weight loss ranges from 37% to 47% for lorcaserin, 35% to 73% for orlistat, and 67% to 70% for top-dose phentermine plus topiramate-extended release. All 3 medications produce greater improvements in many cardiometabolic risk factors than placebo, but no obesity medication has been shown to reduce cardiovascular morbidity or mortality. Most prescriptions are for noradrenergic medications, despite their approval only for short-term use and limited data for their long-term safety and efficacy. Medications approved for long-term obesity treatment, when used as an adjunct to lifestyle intervention, lead to greater mean weight loss and an increased likelihood of achieving clinically meaningful 1-year weight loss relative to placebo. By discontinuing medication in patients who do not respond with weight loss of at least 5%, clinicians can decrease their patients' exposure to the risks and costs of drug treatment when there is little prospect of long-term benefit.

Safety of antiobesity drugs

Obesity is a major health problem worldwide. Although diet and physical activity are crucial in the management of obesity, the long-term success rate is low. Therefore antiobesity drugs are of great interest, especially when lifestyle modification has failed. As obesity is not an immediate life-threatening disease, these drugs are required to be safe. Antiobesity drugs that have been developed so far have limited efficacies and considerable adverse effects affecting tolerability and safety. Therefore, most antiobesity drugs have been withdrawn. Fenfluramine and dexfenfluramine were withdrawn because of the potential damage to heart valves. Sibutramine was associated with an increase in major adverse cardiovascular events in the Sibutramine Cardiovascular Outcomes (SCOUT) trial and it was withdrawn from the market in 2010. Rimonabant was withdrawn because of significant psychiatric adverse effects. Orlistat was approved in Europe and the United States for long-term treatment of obesity, but many patients cannot tolerate its gastrointestinal side effects. Phentermine and diethylpropion can only be used for less than 12 weeks because the long-term safety of these drugs is unknown. Ephedrine and caffeine are natural substances but the effects on weight reduction are modest. As a result there is a huge unmet need for effective and safe antiobesity drugs. Recently lorcaserin and topiramate plus phentermine have been approved for the treatment of obesity but long-term safety data are lacking.

Addiction potential of phentermine prescribed during long-term treatment of obesity

To investigate if phentermine treatment induces phentermine abuse, psychological dependence (addiction) or phentermine drug craving in overweight, obese and weight loss maintenance patients. To investigate whether amphetamine-like withdrawal occurs after abrupt cessation of long-term phentermine treatment. Clinical intervention trial with interruption of phentermine treatment in long-term patients. 269 obese, overweight or formerly obese subjects (age: 20-88 years, BMI: 21-74 kg m(-2)) treated with phentermine long-term (LTP, N=117), 1.1-21.1 years, or short-term (ATP, N=152), 4-22 days, with phentermine doses of 18.75-112.5 (LTP) and 15-93.75 (ATP) mg per day. Module K of the Mini International Neuropsychiatric Interview modified for phentermine (MINI-SUD), Severity of Dependence Scale (SDS), 45-item Cocaine Craving Questionnaire-NOW (CCQ-NOW) modified for phentermine (PCQ-NOW), and Amphetamine Withdrawal Questionnaire (AWQ) modified for phentermine (PWQ). MINI-SUD interviews were negative for phentermine abuse or psychological dependence in all LTP patients. SDS examination scores were low for all LTP and ATP patients, indicating they were not psychologically dependent upon phentermine. PCQ-NOW scores were low for all LTP and ATP patients, indicating neither short-term nor long-term phentermine treatment had induced phentermine craving. Other than an increase in hunger or eating, amphetamine-like withdrawal symptoms did not occur upon abrupt phentermine cessation as measured by sequential PWQ scores. Phentermine abuse or psychological dependence (addiction) does not occur in patients treated with phentermine for obesity. Phentermine treatment does not induce phentermine drug craving, a hallmark sign of addiction. Amphetamine-like withdrawal does not occur upon abrupt treatment cessation even at doses much higher than commonly recommended and after treatment durations of up to 21 years.

Nutrient Deficiencies After Gastric Bypass Surgery

Bariatric surgery, and in particular, gastric bypass, is an increasingly utilized and successful approach for long-term treatment of obesity and amelioration of comorbidities. Nutrient deficiencies after surgery are common and have multiple causes. Preoperative factors include obesity, which appears to be associated with risk for several nutrient deficiencies, and preoperative weight loss. Postoperatively, reduced food intake, suboptimal dietary quality, altered digestion and absorption, and nonadherence with supplementation regimens contribute to risk of deficiency. The most common clinically relevant micronutrient deficiencies after gastric bypass include thiamine, vitamin B₁₂, vitamin D, iron, and copper. Reports of deficiencies of many other nutrients, some with severe clinical manifestations, are relatively sporadic. Diet and multivitamin use are unlikely to consistently prevent deficiency, thus supplementation with additional specific nutrients is often needed. Though optimal supplement regimens are not yet defined, most micronutrient deficiencies after gastric bypass currently can be prevented or treated by appropriate supplementation.

Biological effects of bariatric surgery on obesity-related comorbidities

The prevalence of obesity has increased so rapidly over the last few decades that it is now considered a global epidemic. Obesity, defined as a body mass index (BMI) of 30 or more, is associated with several comorbid conditions that decrease life expectancy and increase health care costs. Diet therapies have been reported to be ineffective in the long-term treatment of obesity, and guidelines for the surgical therapy of morbid obesity (BMI ≥ 40 or BMI ≥ 35 in the presence of substantial comorbidities) have since been established. Considering the number of bariatric surgical procedures has dramatically increased since these guidelines were established, we review the types of bariatric surgical procedures and their impact on diabetes, sleep apnea, dyslipidemia and hypertension - 4 major obesity-related comorbidities.

Long-chain n−3 PUFAs reduce adipose tissue and systemic inflammation in severely obese nondiabetic patients: a randomized controlled trial

Chronic adipose tissue inflammation is a hallmark of obesity, triggering the development of associated pathologies, particularly type 2 diabetes. Long-chain n-3 PUFAs reduce cardiovascular events and exert well-established antiinflammatory effects, but their effects on human adipose tissue inflammation are unknown. We investigated whether n-3 PUFAs reduce adipose tissue inflammation in severely obese nondiabetic patients. We treated 55 severely obese nondiabetic patients, scheduled to undergo elective bariatric surgery, with 3.36 g long-chain n-3 PUFAs/d (EPA, DHA) or an equivalent amount of butterfat as control, for 8 wk, in a randomized open-label controlled clinical trial. The primary efficacy measure was inflammatory gene expression in visceral and subcutaneous adipose tissue samples (subcutaneous adipose tissue and visceral adipose tissue), collected during surgery after the intervention. Secondary efficacy variables were adipose tissue production of antiinflammatory n-3 PUFA-derived eicosanoids, plasma concentrations of inflammatory markers, metabolic control, and the effect of the Pro12Ala PPARG polymorphism on the treatment response. Treatment with n-3 PUFAs, which was well tolerated, decreased the gene expression of most analyzed inflammatory genes in subcutaneous adipose tissue (P < 0.05) and increased production of antiinflammatory eicosanoids in visceral adipose tissue and subcutaneous adipose tissue (P < 0.05). In comparison with control subjects who received butterfat, circulating interleukin-6 and triglyceride concentrations decreased significantly in the n-3 PUFA group (P = 0.04 and P = 0.03, respectively). The Pro12Ala polymorphism affected the serum cholesterol response to n-3 PUFA treatment. Treatment with long-chain n-3 PUFAs favorably modulated adipose tissue and systemic inflammation in severely obese nondiabetic patients and improved lipid metabolism. These effects may be beneficial in the long-term treatment of obesity. This trial was registered at clinicaltrials.gov as NCT00760760.

Overview on Obesity - A Review

Obesity is a global health problem including bangladesh resulting in major morbidity and premature death. The causes of this epidemic are complex and multifactorial, but fundamentally lead to an excess calorie intake over energy expenditure. Modern lifestyles, incorporating altered eating patterns, access to cheap, highly palatable, energy-dense yet nutritionally poor foods, sedentary habits and laborsaving devices, have hugely accelerated the problem during last few years. Till date safe and efficacious drug therapies remains unmet. The two drugs for the long-term treatment of obesity, Orlistat and Sibutramine, provide only modest weight-loss benefits and are associated with high attrition rates owing to side effects. Currently neuroendocrine control of energy homeostasis and major pharmacological treatments for obesity in the pipeline. The discovery of leptin and other gut hormones as major neuroendocrine regulators of bodyweight is leading the way to the development of attractive therapeutic approaches to the long-term manipulation of energy homeostasis in favor of appetite reduction and weight loss. It is hoped that this may be associated with a relative paucity of central or unexpected side effects. The rest of this article will concentrate on these therapeutic strategies. Still shortcomings of medical treatment encouraged the Barriatric surgery specially for morbid obese subjects. Though many advantages are ascribed including remission and improvement of Type 2 diabetes mellitus, long term metabolic and nutritional effects still remains questionable. Comparative data among different procedures of Barriatric surgery are also insufficient. DOI: http://dx.doi.org/10.3329/birdem.v1i1.12384 Birdem Med J 2011; 1(1): 26-29

Short- and Long-Term Eating Habit Modification Predicts Weight Change in Overweight, Postmenopausal Women: Results from the WOMAN Study

BackgroundStandard behavioral obesity treatment produces poor long-term results. Focusing on healthy eating behaviors rather than energy intake may be an alternative strategy. In addition, important behaviors might differ for short- vs long-term weight control. ObjectiveOur aim was to describe and compare associations between changes in eating behaviors and weight after 6 and 48 months. DesignWe performed secondary analysis of data collected during a randomized weight-loss intervention trial with 48-month follow-up. ParticipantsWe studied 481 overweight and obese postmenopausal women enrolled in the Women on the Move through Activity and Nutrition (WOMAN) Study. Main outcome measuresWe measured changes in weight from baseline to 6 and 48 months. Statistical analyses performedLinear regression models were used to examine the associations between 6- and 48-month changes in eating habits assessed by the Conner Diet Habit Survey and changes in weight. Analyses were conducted in the combined study population and stratified by randomization group. ResultsAt 6 months in the combined population, weight loss was independently associated with decreased desserts (P<0.001), restaurant eating (P=0.042), sugar-sweetened beverages (P=0.009), and fried foods (P<0.001), and increased fish consumption (P=0.003). Results were similar in intervention participants; only reduced desserts and fried foods associated with weight loss in controls. At 48 months in the combined population, weight loss was again associated with decreased desserts (P=0.003) and sugar-sweetened beverages (P=0.011), but also decreased meats/cheeses (P=0.024) and increased fruits/vegetables (P<0.001). Decreased meats/cheeses predicted weight loss in intervention participants; desserts, sugar-sweetened beverages, and fruits/vegetables were independently associated in controls. ConclusionsChanges in eating behaviors were associated with weight change, although important behaviors differed for short- and long-term weight change and by randomization group. Future studies should determine whether interventions targeting these behaviors could improve long-term obesity treatment outcomes.

What Cost Weight Loss?

Obesity has important adverse health consequences associated with multiple metabolic, structural, degenerative, neoplastic, and psychological effects that reduce quality of life and increase mortality.1 Given the epidemic of obesity in the United States and worldwide, treatment of obesity has emerged as 1 of the greatest present unmet medical needs and a target for pharmacological interventions. Factors underlying the population's rapid increase in excess weight, as well as reasons for difficulty achieving and sustaining weight loss, remain incompletely understood. Medications have been used to assist in weight loss for almost 80 years, but adverse effects frequently restrict their utility. Norepinephrine reuptake inhibitors are available for short-term administration to promote weight loss, but weight regain is common when use is discontinued. The weight loss drugs fenfluramine and dexfenfluramine, intended for long-term use, were removed from the US market in 1997 because of the occurrence of left-sided valvular heart disease; phenylpropanolamine was withdrawn in 2000 for its association with hemorrhagic stroke; and rimonabant was available briefly in Europe but was withdrawn because of its association with depression and suicidal ideation before its approval in the United States. Currently, there is only 1 medication (orlistat) approved for the long-term treatment of obesity by the US Food and Drug Administration (FDA) after the recent voluntary withdrawal of sibutramine from the US market. In contrast, surgical treatments for obesity have become important alternatives to pharmacotherapy, especially since the advent of less invasive laparoscopic techniques.2 Surgically induced weight loss is often substantial and is associated with improvements in obesity-related diseases such as diabetes mellitus, hypertension, dyslipidemia, and obstructive sleep apnea, as well as with reductions in cancer risk and mortality.3–6 With the development of less invasive techniques, apparent reduced procedure-related morbidity, and the absence of alternatives, bariatric surgical procedures are being performed …

Candidates for Bariatric Surgery: Morbidly Obese Patients with Pulmonary Dysfunction

Obesity is a well-known major risk factor of cardiovascular disease and is associated with various comorbidities. The impact of obesity on pulmonary function remains unclear. Reductions in chest wall compliance and respiratory muscle strength due to a high percent body fat and localized fat distribution contributes to impaired pulmonary function and the occurrence of adverse respiratory symptoms. Dietary modifications and pharmaceutical agents are not effective in the long-term treatment of obesity. Treatment of morbidly obese patients using bariatric surgery has increased each year, especially after the introduction of video laparoscopic techniques. Effective weight loss after bariatric surgery may improve cardiovascular disease risk factors, including diabetes, hypertension, dyslipidemia, atherosclerosis, inflammation, chronic kidney disease, obstructive sleep apnea, and obesity hypoventilation syndrome. Bariatric surgery has also been associated with significantly improved respiratory symptoms and pulmonary function. We currently present a review of principal studies that evaluated the effects of obesity on pulmonary function and the identification of anthropometric factors of obesity that correspond to the reversal of respiratory symptoms and impaired pulmonary function after bariatric surgery.

Intragastric Balloon in Association with Lifestyle and/or Pharmacotherapy in the Long-Term Management of Obesity

Intragastric balloon (BioEnterics Intragastric Balloon, BIB®) or pharmacotherapy are possible options for the treatment of obese patients when traditional approaches have failed. The aim of our study was to compare in obese patients the effect on weight loss and metabolic changes of lifestyle modifications associated with either BIB or pharmacotherapy or the two treatments in sequence as a maintenance strategy for weight loss. Fifty obese patients were recruited and randomly assigned to lifestyle modifications combined with either BIB for 6months (n = 30) or sibutramine (pharmacotherapy group) for 1year (n = 20). After BIB removal, patients were randomly assigned to either correct lifestyle (BIB/lifestyle) or lifestyle plus pharmacotherapy (BIB/pharmacotherapy). At 6months, patients treated with BIB lost significantly (P < 0.05) more weight (percent of initial weight lost, %IWL = 14.5 ± 1.2; percent of excess BMI lost, %EBL = 37.7 ± 3.2) than patients who received pharmacological treatment (%IWL = 9.1 ± 1.5, %EBL = 25.3 ± 4.1). At 1year, the weight lost was significantly (P < 0.05) greater in patients treated with either BIB/pharmacotherapy (%IWL = 15.8 ± 2.3%, %EBL = 41.3 ± 6.7%) or BIB/lifestyle (%IWL = 14.3 ± 2.7, %EBL = 34.9 ± 6.5%) in respect to pharmacotherapy group (%IWL = 8.0 ± 1.4%, %EBL = 22.1 ± 3.9%). Moreover, patients treated sequentially with BIB/lifestyle or BIB/pharmacotherapy showed a significant (P < 0.05) improvement in insulin sensitivity and triglycerides levels. BIB represents an efficacious long-term obesity treatment when supplemental strategies, as lifestyle modifications or pharmacotherapy, are established for weight maintenance after its removal.

Food reward functions as affected by obesity and bariatric surgery

Roux-en-Y gastric bypass surgery (RYGB) remains to be the most effective long-term treatment for obesity and its associated comorbidities, but the specific mechanisms involved remain elusive. Because RYGB patients appear to no longer be preoccupied with thoughts about food and are satisfied with much smaller meals and calorically dilute foods, brain reward mechanisms could be involved. Just as obesity can produce maladaptive alterations in reward functions, reversal of obesity by RYGB could normalize these changes or even further reset the food reward system through changes in gut hormone secretion, aversive conditioning and/or secondary effects of weight loss. Future studies with longitudinal assessments of reward behaviors and their underlying neural circuits before and after surgery will be necessary to uncover the specific mechanisms involved. Such new insights could be the base for future 'knifeless' pharmacological and behavioral approaches to obesity.

Treating Obesity in the Family Practice Setting

The health risks of obesity include the development of comorbid conditions and increased overall mortality. Obesity increases health-related costs for both patients and the healthcare system and significantly affects workforce productivity through increased absenteeism and higher health and insurance payments for employers. Discrimination against obese individuals exists in the workplace and in various social contexts. Obesity is a chronic condition with complex, multiple causes involving physiologic, genetic, and behavioral components, all of which must be addressed for successful treatment. Traditional treatment options include diet, exercise, and behavior modification, but recently, pharmacotherapy has been incorporated as an effective and safe adjunct for long-term treatment of obesity. Additionally, bariatric surgery is an option for selected morbidly obese individuals. Weight losses of only 5% to 10% of initial body weight confer proven clinical benefits. Such modest weight losses can be achieved and maintained within a supportive environment provided in a primary care practice.