Weight loss through ileal transposition is accompanied by increased ileal hormone secretion and synthesis in rats

Bariatric surgeries, such as gastric bypass, result in dramatic and sustained weight loss that is usually attributed to a combination of gastric volume restriction and intestinal malabsorption. However, studies parceling out the contribution of enhanced intestinal stimulation in the absence of these two mechanisms have received little attention. Previous studies have demonstrated that patients who received intestinal bypass or Roux-en-Y surgery have increased release of gastrointestinal hormones. One possible mechanism for this increase is the rapid transit of nutrients into the intestine after eating. To determine whether there is increased secretion of anorectic peptides produced in the distal small intestine when this portion of the gut is given greater exposure to nutrients, we preformed ileal transpositions (IT) in rats. In this procedure, an isolated segment of ileum is transposed to the jejunum, resulting in an intestinal tract of normal length but an alteration in the normal distribution of endocrine cells along the gut. Rats with IT lost more weight (P < 0.05) and consumed less food (P < 0.05) than control rats with intestinal transections and reanastomosis without transposition. Weight loss in the IT rats was not due to malabsorption of nutrients. However, transposition of distal gut to a proximal location caused increased synthesis and release of the anorectic ileal hormones glucagon-like peptide-1 (GLP-1) and peptide YY (PYY; P < 0.01). The association of weight loss with increased release of GLP-1 and PYY suggests that procedures that promote gastrointestinal endocrine function can reduce energy intake. These findings support the importance of evaluating the contribution of gastrointestinal hormones to the weight loss seen with bariatric surgery.     

Operation Everest. II: Nutrition and body composition

Progressive body weight loss occurs during high mountain expeditions, but whether it is due to hypoxia, inadequate diet, malabsorption, or the multiple stresses of the harsh environment is unknown. To determine whether hypoxia due to decompression causes weight loss, six men, provided with a palatable ad libitum diet, were studied during progressive decompression to 240 Torr over 40 days in a hypobaric chamber where hypoxia was the major environmental variable. Caloric intake decreased 43.0% from 3,136 to 1,789 kcal/day (P less than 0.001). The percent carbohydrate in the diet decreased from 62.1 to 53.2% (P less than 0.001). Over the 40 days of the study the subjects lost 7.4 +/- 2.2 (SD) kg and 1.6% (2.5 kg) of the total body weight as fat. Computerized tomographic scans indicated that most of the weight loss was derived from fat-free weight. The data indicated that prolonged exposure to the increasing hypoxia was associated with a reduction in carbohydrate preference and body weight despite access to ample varieties and quantities of food. This study suggested that hypoxia can be sufficient cause for the weight loss and decreased food consumption reported by mountain expeditions at high altitude.     

Roux-en-Y gastric bypass and laparoscopic sleeve gastrectomy: understanding weight loss and improvements in type 2 diabetes after bariatric surgery

Obesity increases the likelihood of diseases like type 2 diabetes (T2D), heart disease, and cancer, and is one of the most serious public health problems of this century. In contrast to ineffectual prevention strategies, lifestyle modifications, and pharmacological therapies, bariatric surgery is a very effective treatment for morbid obesity and also markedly improves associated comorbidities like T2D. However, weight loss and resolution of T2D after bariatric surgery is heterogeneous and specific to type of bariatric procedure performed. Conventional mechanisms like intestinal malabsorption and gastric restriction do not fully explain this, and potent changes in appetite and the enteroinsular axis, as a result of anatomical reorganization and altered hormonal, neuronal, and nutrient signaling, are the portended cause. Uniquely these signaling changes appear to override vigorous homeostatic defenses of stable body weight and compelling self-gratifying motivations to eat and to reverse defects in beta-cell function and insulin sensitivity. Here we review mechanisms of weight loss and T2D resolution after Roux-en-Y gastric bypass and laparoscopic sleeve gastrectomy bariatric surgery, two markedly different procedures with robust clinical outcomes.     

Gastric Bypass in a Low‐Income,Inner‐City Population: Eating Disturbances and Weight Loss

Objective: To examine the prevalence of eating disturbances and psychiatric disorders among extremely obese patients before and after gastric bypass surgery and to examine the relationship between these disturbances and weight outcomes. Research Methods and Procedures: Sixty‐five women patients (ages 19 to 67) with a mean BMI of 54.1 were assessed by semistructured psychiatric interview before surgery and by telephone interview after surgery (mean follow‐up: 16.4 months) to determine psychiatric status, eating disturbances, and weight and health‐related variables. Results: Patients lost a mean of 71% of their excess BMI, with significantly poorer weight loss outcomes among African Americans. Psychiatric disorders remained prevalent before (37%) and after (41%) surgery. In contrast, binge eating disorder dropped from 48% to 0%. Psychiatric diagnosis did not affect weight outcomes. Instead, more frequent preoperative binge eating, along with greater initial BMI, follow‐up length, and postoperative exercise, predicted greater BMI loss. Postsurgical health behaviors (exercise and smoking) and nocturnal eating episodes were also linked to weight loss. Exercise frequency increased and smoking frequency tended to decrease after surgery. Discussion: These findings indicated that eating and psychiatric disturbances did not inhibit weight loss after gastric bypass and should not contraindicate surgery. Prior binge eating, eliminated after surgery, predicted BMI loss and, thus, may have previously been a maintaining factor in the obesity of these patients. The association between health behaviors and outcome suggests possible targets for intervention to improve surgical results. Poorer outcomes among African Americans indicate that these patients should be closely monitored and supported after surgery.     

Oxalate nephropathy due to gastrointestinal disorders.

Renal failure secondary to oxalate interstitial nephritis developed in three patients with malabsorption and steatorrhea following a jejunoileal bypass, extensive small intestine resection and a partial gastrectomy. Hyperoxaluria was documented in two of the cases. The possibility that this complication can occur in patients after a jejunoileal bypass operation is now recognized. This report shows that it can also occur in patients with other bowel disorders that cause malabsorption and steatorrhea. Since the prognosis for patients with oxalate nephropathy is poor, renal function should be closely monitored in patients who are at risk because of these disorders. Therapy should be directed at correcting malabsorption, steatorrhea and hyperoxaluria. When the renal function of patients with a jejunoileal bypass continues to decline despite intensive medical therapy, restoration of bowel continuity is strongly recommended.     

Roux‐en‐Y Gastric Bypass Enhances Energy Expenditure and Extends Lifespan in Diet‐induced Obese Rats

Gastrointestinal weight‐loss surgery (GIWLS) is currently the most effective treatment for severe obesity, with Roux en‐Y gastric bypass (RYGB) among the best of the available surgical options. Despite its widespread clinical use, the mechanisms by which RYGB induces its profound weight loss remain largely unknown. This procedure effects weight loss by altering the physiology of weight regulation and eating behavior rather than by simple mechanical restriction and/or malabsorption as previously thought. To study how RYGB affects the physiology of energy balance, we developed a rat model of this procedure. In this report, we demonstrate that RYGB in diet‐induced obese (DIO) rats induces a 25% weight loss, prolongs mean survival by 45%, and normalizes glucose homeostasis and lipid metabolism. RYGB induced a 19% increase in total and a 31% increase in resting energy expenditure (REE). These effects, along with a 17% decrease in food intake and a 4% decrease in nutrient absorption account for the normalization of body weight after this procedure. These effects indicate that surgery acts by altering the physiology of weight regulation and help to explain the effectiveness of RYGB in comparison to restrictive dieting and other forms of dietary and pharmacological therapies for obesity. The clinical effectiveness of RYGB and its physiological effects on body weight regulation and energy expenditure (EE) suggest that this operation provides a unique opportunity to explore the mechanisms of energy homeostasis and to identify novel therapies for obesity and related metabolic diseases.     

New aspects in the management of obesity: operation and the impact of lipase inhibitors

Obesity is an increasing health problem in most developed countries and its prevalence is also increasing in developing countries. There has been no great success with dietary means and life style modification for permanent weight loss. Various surgical treatment methods for obesity are now available. They are aimed at limiting oral energy intake with or without causing dumping or inducing selective maldigestion and malabsorption. Based on current literature, up to 75% of excess weight is lost by surgical treatment with concomitant disappearance of hyperlipidaemias, type 2 diabetes, hypertension or sleep apnoea. The main indication for operative treatment is morbid obesity (body mass index greater than 40 kg/m2) or severe obesity (body mass index > 35 kg/m2) with comorbidities of obesity. Orlistat is a new inhibitor of pancreatic lipase enzyme. At doses of 120 mg three times per day with meals it results in a 30% reduction in dietary fat absorption, which equals approximately 200 kcal daily energy deficit. In the long term, orlistat has been shown to be more effective than placebo in reducing body weight and serum total and low-density lipoprotein cholesterol levels. Orlistat has a lowering effect on serum cholesterol independent of weight loss. Along with weight loss, orlistat also favourably affects blood pressure and glucose and insulin levels in obese individuals and in obese type 2 diabetic patients.     

High allelic burden of four obesity SNPs is associated with poorer weight loss outcomes following gastric bypass surgery

Genome‐wide association and linkage studies have identified multiple susceptibility loci for obesity. We hypothesized that such loci may affect weight loss outcomes following dietary or surgical weight loss interventions. A total of 1,001 white individuals with extreme obesity (BMI >35 kg/m²) who underwent a preoperative diet/behavioral weight loss intervention and Roux‐en‐Y gastric bypass surgery were genotyped for single‐nucleotide polymorphisms (SNPs) in or near the fat mass and obesity‐associated (FTO), insulin induced gene 2 (INSIG2), melanocortin 4 receptor (MC4R), and proprotein convertase subtilisin/kexin type 1 (PCSK1) obesity genes. Association analysis was performed using recessive and additive models with pre‐ and postoperative weight loss data. An increasing number of obesity SNP alleles or homozygous SNP genotypes was associated with increased BMI (P < 0.0006) and excess body weight (P < 0.0004). No association between the amounts of weight lost from a short‐term dietary intervention and any individual obesity SNP or cumulative number of obesity SNP alleles or homozygous SNP genotypes was observed. Linear mixed regression analysis revealed significant differences in postoperative weight loss trajectories across groups with low, intermediate, and high numbers of obesity SNP alleles or numbers of homozygous SNP genotypes (P < 0.0001). Initial BMI interacted with genotype to influence weight loss with initial BMI <50 kg/m², with evidence of a dosage effect, which was not present in individuals with initial BMI ≥50 kg/m². Differences in metabolic rate, binge eating behavior, and other clinical parameters were not associated with genotype. These data suggest that response to a surgical weight loss intervention is influenced by genetic susceptibility and BMI.     

Protein absorption and energy digestibility at high altitude.

To test the hypothesis that malabsorption of dietary protein is partly responsible for the weight loss observed during prolonged altitude exposure, six healthy male subjects [31.8 +/- 4.5 (SD) yr] received 15N-labeled soya protein by mouth and [15N]glycine intravenously at 122 and 5,000 m. From the subsequent 4-day total urine and fecal pools, the different fractions of the administered 15N were determined by mass spectrometry. Weight and skinfold thickness were measured at the beginning and end of the altitude exposure. In addition, the overall digestible energy of the diet at altitude was assessed by a 3-day diet control and adiabatic bomb calorimetric assessment of the energy content of the corresponding fecal pool. The average decrease of the subjects' weight during altitude exposure was 3%. Loss of fat mass at altitude estimated from the skinfold measurements was 9%. Protein absorption, calculated as 100--[fecal excretion of 15N after ingestion of 15N soya protein (% of dose given)--fecal excretion of 15N after injection of 15N glycine (% of dose given)], was not significantly impaired at altitude compared with sea level (96 vs. 97%, respectively), and overall digestible energy at altitude, calculated as 100--percent undigested gross energy in the feces, amounted to 96%. It is concluded that, at least up to an altitude of 5,000 m, malabsorption does not play a role in altitude-related weight loss.     

Partial consumption of prey: the significance of prey water loss on estimates of biomass intake

Summary A number of studies on the feeding behaviour of sucking predators have estimated the weight of biomass the predator extracts from the prey by measuring the weight change occurring in the prey. This method does not consider that a proportion of the prey weight change is lost to the immediate environment. I examined the spider Diaea sp. feeding on the fruit fly Drosophila immigrans and found that the prey lost approximately 28% more weight than the predator gained. This difference was largely explained by water loss from the prey. My results suggest that water loss, which is not available to the predator, is an important part of prey weight loss. To avoid overestimating predator biomass gain it is necessary to measure the predator weight gain directly or take into account water loss as a component of prey weight change.     

Randomized double‐blind placebo‐controlled study of leptin administration after gastric bypass

Objective:

Obese individuals have high levels of circulating leptin and are resistant to the weight‐reducing effect of leptin administration at physiological doses. Although Roux‐en‐Y gastric bypass (RYGB) is an effective weight loss procedure, there is a plateau in weight loss and most individuals remain obese. This plateau may be partly due to the decline in leptin resulting in a state of relative leptin insufficiency. The main objective of this study was to determine whether leptin administration to post‐RYGB patients would promote further weight reduction.

Design and Methods:

This was a randomized, double‐blind, placebo‐controlled cross‐over study of 27 women who were at least 18 months post‐RYGB and lost on average 30.8% of their presurgical body weight. Subjects received either leptin or placebo via subcutaneous injection twice daily for 16 weeks, then crossed over to receive the alternate treatment for 16 weeks.

Results:

Weight change after 16 weeks of placebo was not significantly different from that after 16 weeks of leptin. No changes were observed in percent fat mass, resting energy expenditure, thyroid hormones, or cortisol levels.

Conclusion:

Contrary to our hypothesis, we did not observe a significant effect of leptin treatment on body weight in women with relative hypoleptinemia after RYGB.     

Treatment of Gross Obesity by Jejunal Bypass

Jejunal bypass operations were performed on 47 grossly obese patients. The results were disappointing in three patients who had a standard “14 in/4 in” Payne and DeWind procedure and therefore a more radical operation was performed, joining four inches (10·2 cm) of proximal jejunum to 10 inches (24·4 cm) of terminal ileum. Two years after the modified operation a mean of 44·2 kg had been lost and the weight tended to stabilize. This weight loss was due mainly to inadequate calorie intake. The appetite became more controlled so that if weight was regained this was small in amount. Metabolic sequelae and their symptoms also settled by two years. The physical, psychological, and social outcome was good. The postoperative period was stormy and required close medical and psychiatric supervision. There were two deaths.     

Severe peripheral neuropathy following gastric bypass surgery for morbid obesity.

Severe weakness in the limbs developed in a young woman 3 1/2 months after successful gastric bypass surgery for morbid obesity. Electromyography confirmed the clinical impression of generalized axonal polyneuropathy. Vitamin B replacement therapy was started. The gastric bypass was not reversed, and the patient continued to lose weight while undergoing rehabilitation. After 10 months she had almost fully recovered. Her total weight loss was 76 kg. Neuropathy is an uncommon but serious complication of semistarvation that should be preventable by routine administration of vitamin B complex.     

Hepatic structure and function after modified jejunoileal bypass surgery for obesity.

The most serious adverse effect of standard intestinal bypass for obesity is the high incidence of hepatic dysfunction and death from hepatic failure. We therefore examined the long-term effects of a modified form of jejunoileal bypass (in which a greater continuous length of ileum is retained), on liver function in 120 patients. Substantial weight loss (119-0+/-SD 23-3 kg to 82-3+/-18-8 kg) occurred during the first nine months after surgery, accompanied by a significant rise in serum concentrations of bilirubin, alanine transferase, and alkaline phosphatase, and a significant reduction in albumin concentrations. Biochemical changes were unrelated to weight loss or halothane anaesthesia. After weight stabilisation liver function reverted to normal, and four years after bypass sulphobromophthalein retention and hepatic histology did not differ from those in obese controls. There were two postoperative deaths. Three other patients died during the period of rapid weight loss with severe hepatic steatosis. While transient mild impairment of liver function is common after modified jejunoileal bypass, clinically significant hepatic dysfunction is a rare and unexplained early complication.     

Validity of weight loss to estimate improvement in body composition in individuals attending a wellness center

The accuracy of weight loss in estimating successful changes in body composition (BC), namely fat mass (FM) loss, is not known and was addressed in our study. To assess the correlation between change in body weight and change in FM, fat% and fat‐free mass (FFM), 465 participants (41% male; 41 ± 13 years), who met the criteria for weight change assessment at a wellness center, underwent air‐displacement plethysmography (ADP). Body weight and BC were measured at the same time. We categorized the change in body weight, FM and FFM as an increase if there was >1 kg gain, a decrease if there was >1 kg loss and no change if the difference was ≤1 kg. We estimated the diagnostic performance of weight change to identify improvement in BC. After a median time of 132 days, there was a mean weight change was 2.4 kg. From the 255 people who lost >1 kg of weight, 216 (84.7%) had lost >1 kg of FM, but 69 (27.1%) had lost >1 kg of FFM. Of the 143 people with no weight change, 42 (29.4%) had actually lost >1 kg of FM. Of the 67 who gained >1 kg of weight at follow‐up, in 23 (34.3%) this was due to an increase in FFM but not in FM. Weight change had a NPV of 73%. Our results indicate that favorable improvements in BC may go undetected in almost one‐third of people whose weight remains the same and in one‐third of people who gain weight after attending a wellness center. These results underscore the potential role of BC measurements in people attempting lifestyle changes.     

Effect of weight loss on the rate of muscle protein synthesis during fasted and fed conditions in obese older adults

Although weight loss ameliorates many of the metabolic abnormalities associated with obesity, there has been reluctance to prescribe weight loss in obese, older individuals because of the fear that it will cause debilitating loss of muscle mass and impair physical function. To gain insight into the mechanisms responsible for the weight loss-induced changes in muscle mass, we measured the rate of muscle protein synthesis (by using stable isotope labeled tracer methodology) during basal, postabsorptive conditions and during mixed meal ingestion in eight obese, older adults: (i) before weight loss therapy, (ii) ~3 months after starting the weight loss intervention (i.e., during the active weight loss phase), when subjects had lost ~7% of their initial body weight, and (iii) after they had lost ~10% of their body weight and maintained this new body weight for ~6 months (~12 months after starting the weight loss intervention). The basal muscle protein fractional synthesis rate (FSR) was not affected by weight loss. Mixed meal ingestion stimulated the rate of muscle protein synthesis, and the anabolic response (i.e., increase in the protein synthesis rate above basal values) was greater (P < 0.05) during negative energy balance and active weight loss at 3 months (0.033 ± 0.012%·per hour, mean ± s.e.m.) than during weight maintenance before and at 12 months of weight loss therapy (0.003 ± 0.003 and 0.008 ± 0.012%·per hour, respectively). We conclude that during dietary calorie restriction and weight loss in older adults, the rate of muscle protein synthesis is not impaired. Thus, the loss of muscle mass must be mediated predominately by adverse effects of dietary calorie restriction on muscle proteolysis.     

Intestinal protozoa and epithelial cell kinetics, structure and function

Intestinal protozoa are not only common enteric pathogens in the tropics but also the high incidence of infection among immunocompromised patients in northern countries has evoked an increased interest in these parasites. Although enteric protozoa are a major cause of diarrhea and malabsorption in humans and other animals, the pathophysiology of gut disturbances caused by them remains poorly understood. Clinical signs related to enteric protozoan disease commonly involve malabsorption, diarrhea, weight loss or retarded weight gain and anorexua. Since these infections are most prevalent and most severe in the young, this may translate into considerable illness among children and significant loss to the agricultural economy where domestic animals are prone to infection. In this review we describe the effects of intestinal protozoan diseases on the structure, kinetics and function of absorptive intestinal cells and other epithelial cells, and correlate morphological injury with physiological alterations in the parasitized gut. Some of the interactions between immune responses and pathophysiology will be discussed, but in-depth discussion of intestinal immunity has recently been undertaken by other authors.     

Plasma fenfluramine levels,weight loss,and side effects.

Fifty women with refractory obesity received fenfluramine for 20 weeks. Every two weeks details of weight change, drug dose, degree of anorexia, and any side effects were recorded and plasma was obtained for fenfluramine and norfenfluramine measurements. Of the 41 patients available for final analysis 26 achieved a maximum plateau dose of 160 mg/day. Plasma fenfluramine concentrations did not correlate with the degree of anorexia or with the incidence of side effects other than the severity of dream disturbance. There was a highly significant relation between weight loss and plasma fenfluramine and norfenfluramine concentrations and also between weight loss and the presence of sustained anorexia. Women who achieved mean plateau concentrations over 200 ng/ml lost a mean 8.8 kg while those with concentrations less than 100 ng/ml lost a mean of only 2.1 kg. When fenfluramine is prescribed in refractory obesity the dose should be increased stepwise until either satisfactory weight loss is achieved or troublesome side effects appear.     

Capacity for physical activity predicts weight loss after Roux-en-Y gastric bypass

Despite its overall excellent outcomes, weight loss after Roux-en-Y gastric bypass (RYGB) is highly variable. We conducted this study to identify clinical predictors of weight loss after RYGB. We reviewed charts from 300 consecutive patients who underwent RYGB from August 1999 to November 2002. Data collected included patient demographics, medical comorbidities, and diet history. Of the 20 variables selected for univariate analysis, 9 with univariate P values 相似文献   

Effectiveness of a Prebariatric Surgery Insurance‐required Weight Loss Regimen and Relation to Postsurgical Weight Loss

Most US insurance companies require patients to participate in a medically supervised weight loss regimen prior to bariatric surgery. However, the utility of this requirement has not been documented. Data was collected from 94 bariatric surgery patients who were required, and 59 patients who were not required, by their insurance company to participate in a presurgical weight loss regimen. Weight change in the required group, as well as group differences in weight change, was examined from 3 and 6 months presurgery to 1 week presurgery, and from 1 week presurgery to 3 months postsurgery. Weight change presurgery was then used to predict weight loss postsurgery. In the 6 months prior to surgery, required patients gained 3.7 kg ± 5.9 (s.d.) (P < 0.0005), which did not differ from nonrequired patients. From surgery to 3 months postsurgery, required patients lost 23.6 ± 8 kg (P < 0.0005), also without differing from nonrequired patients. Patients who gained more weight prior to surgery, lost more weight postsurgery (P = 0.001), while controlling for initial weight. Findings suggest that the common weight loss regimen requirements of US insurance carriers were ineffective in producing presurgical weight loss in this sample. Most patients (>70%) in this sample gained weight prior to surgery, potentially taking advantage of final opportunities to overindulge in preferred foods. Required patients fared no better in terms of weight change postsurgically and, surprisingly, presurgical weight gain predicted better postsurgical weight loss outcome. Several potential explanations for this finding are offered.