Further lowering of muscle lipid oxidative capacity in obese subjects after biliopancreatic diversion

A reduced lipid oxidative capacity is considered a risk factor for the development of obesity, but a further impairment of lipid oxidative capacity is observed after weight loss. We aimed to define the mechanisms underlying this phenomenon in skeletal muscle and in particular to study the mitochondrial and peroxisomal lipid oxidative pathways. Thus we measured intramyocellular triglyceride content (IMTG) and the expression of genes of lipid oxidation [peroxisome proliferator-activated receptor-alpha, carnitine palmitoyltransferase 1B, and acyl-coenzyme A (acyl-CoA) oxidase 1] and synthesis (acetyl-CoA carboxylase B) using RT-PCR analysis in muscle biopsies of morbidly obese patients before and after biliopancreatic diversion. Weight reduction significantly decreased IMTG while increasing insulin sensitivity, measured by euglycemic hyperinsulinemic clamp. Moreover, an increase in glucose and a decline in lipid oxidation, as assessed by respiratory chamber, were observed. Weight loss reduced the expression of peroxisome proliferator-activated receptor-alpha (-46.7%), carnitine palmitoyltransferase 1B (-43.1%), acyl-CoA oxidase 1 (-37.8%), and acetyl-CoA carboxylase B (-48.7%). Our results indicate that a defect of both peroxisomal and mitochondrial oxidative pathways at the muscular level may contribute to the reduced fat oxidation in obese subjects after biliopancreatic diversion. They also suggest that a depression of the de novo lipogenesis may account for IMTG depletion.     

Resting energy expenditure and body composition in morbidly obese,obese and control subjects

Resting energy expenditure (REE) was investigated by indirect calorimetry in relation to body composition and to different degrees of obesity in order to assess if a defective energy expenditure contributes to extra body fat accumulation. Differences were found between control subjects (group C; BMI 23±0.5 kg/m², REE 5890±218 kJ/day; mean±SEM) and obese subjects (group O; BMI 34.2±0.9 kg/m², REE 7447±360 kJ/day;P<0.0001) and between group C and morbidly obese subjects (group MO; BMI 49.9±1.6 kg/m², REE 8330±360 kJ/day;P<0.0001); REE was not significantly different between groups O and MO. Body composition data were obtained by means of body impedance analysis. Even though group MO had a fat mass higher than group O, body cell mass, the metabolically active body compartment, was similar in groups O and MO, and this fact may have contributed to the similar REE in the two groups. Multiple regression analysis gave the following equation as the best predictor of REE: REE (kJ/day)+1591±49_BW+74_BCM–737 _G (R ²=0.88), where BW is body weight, BCM is body cell mass andG is a dummy variable coding group membership (group C=1; group O=2; group MO=3). Thus the analysis showed a negative impact of obesity on REE beyond body composition variables.     

Growth hormone secretion and leptin in morbid obesity before and after biliopancreatic diversion: relationships with insulin and body composition

Obesity is characterized by increased leptin levels and insulin resistance, whereas blunted GH secretion is paired with normal, low, or high plasma IGF-I levels. To investigate body composition in human obesity and the interactions among the GH-IGF-I axis, leptin, and insulin resistance [measured with the homeostasis model assessment (HOMA) score], we studied 15 obese females, aged 23-54 yr (mean age, 42.7 +/- 2.6), with a body mass index (BMI) of 44.02 +/- 1.45 kg/m(2), who underwent treatment by biliopancreatic diversion (BPD), before and after surgery (16-24 months; BMI, 28.29 +/- 0.89 kg/m(2)). Our controls were 15 normal females, aged 28-54 yr (mean age, 40.8 +/- 2.3 yr), with a BMI of 27.52 +/- 0.53 kg/m(2). Insulin and leptin levels and HOMA scores were higher pre-BPD than in the controls. The GH response to GHRH was blunted, with a GH peak and GH area under the curve (AUC) significantly lower than those in controls. IGF-I and IGF-binding protein-3 (IGFBP-3) were also lower than control values. After surgery, BMI, fat mass, lean body mass, HOMA, insulin, and leptin significantly decreased. Furthermore, the GH response to GHRH severely increased; IGF-I and IGFBP-3 levels did not significantly vary. Considering all subjects, correlation analysis showed a strong positive correlation between insulin and leptin, and a negative correlation between insulin and GH peak and between insulin and GH AUC. Regression analysis performed grouping pre- and post-BPD indicated that leptin and GH peak or AUC could best be predicted from insulin levels. The surgical treatment of severe obesity after stabilization of body weight decreases BMI and fat mass while preserving normal lean body mass as well as positively influencing insulin sensitivity and thus aiding the normalization of leptin levels. The insulin reduction may be mainly involved in the increase in the GH response to GHRH through various possible central and peripheral mechanisms while decreasing the peripheral sensitivity to GH itself, as shown by the stable nature of the IGF-I and IGFBP-3 values. Our findings suggest that the changes in insulin levels are the starting point for changes in both leptin levels and the somatotrope axis after BPD.     

Lipoprotein sub-fraction levels and composition in obese subjects before and after gastroplasty.

Obesity is frequently associated with several alterations of plasma lipid levels and lipoprotein metabolism. To evaluate the effects of severe obesity and weight loss on plasma lipoprotein sub-class levels and composition 11 grossly obese patients were examined before and six and 12 months after gastroplasty. Plasma lipoproteins were isolated by ultracentrifugation in a zonal rotor under rate flotation conditions. Mean body weight was 121.9 kg before gastroplasty, 97.6 kg after six months, and 90.7 kg after 12 months. Total plasma cholesterol was not affected by the weight reduction. Obese patients were characterized by increased levels of IDL and small dense LDL (LDL3). LDL levels, but not LDL3, were reduced following weight reduction. Plasma apo B levels of obese patients were always higher than in controls and were not affected by the weight reduction. After 12 month's weight loss total HDL cholesterol increased without modification of HDL sub-class cholesterol distribution, which was similar to that of normal controls. Plasma apo AI in obese patients was not affected by changes in body weight, and remained below normal. The percentage protein-lipid composition of LDL2 and HDL3 in obese patients was characterized by a decreased cholesterol ester content before gastroplasty which was normalized 12 months after gastroplasty. The presence of IDL and LDL3 in increased concentrations in severely obese patients may represent a vascular risk factor since similar abnormalities were recently observed in non-obese patients affected with vascular diseases.     

Changes in predicted cardiovascular disease risk after biliopancreatic diversion surgery in severely obese patients

Objective

To determine the impact of biliopancreatic diversion with duodenal switch (BPD-DS) surgery on cardiovascular risk profile and predicted cardiovascular risk in severely obese patients.

Materials/Methods

We compared 1-year follow-up anthropometric and metabolic profiles in severely obese who underwent BPD-DS (n = 73) with controls (severely obese without surgery) (n = 33). The 10-year predicted risk for coronary heart disease (CHD) was estimated using the Framingham risk-tool. We assigned 10-year and lifetime predicted risks to stratify subjects into 3 groups: 1) high short-term predicted risk (≥ 10% 10-year risk or diagnosed diabetes), 2) low short-term (< 10% 10-year risk)/low lifetime predicted risk or 3) low short-term/high lifetime predicted risk.

Results

During the follow-up period, body weight and body mass index decreased markedly in the surgical group (− 52.1 ± 1.9 kg and − 19.0 ± 0.6 kg/m² respectively, p < 0.001) vs. (− 0.7 ± 1.0 kg and − 0.3 ± 0.4 kg/m², p = 0.51). Weight loss in the surgical group was associated with a reduction in HbA_1C (6.2% vs. 5.1%), HOMA-IR (61.5 vs. 9.3), all lipoprotein levels, as well as blood pressure (p < 0.001). The 10-year CHD predicted risk decreased by 43% in women and 33% in men, whereas the estimated CHD risk in the non surgical group did not change. Before surgery, none of the women and only 18% of men showed low short-term/low lifetime predicted risk, whereas a significant proportion of subjects had high short-term predicted risk (36% in women and 12% in men). Following surgery, 52% of women and 55% of men have a low short-term/low lifetime predicted risk.

Conclusions

These results highlight the cardiovascular benefits of BPD-DS and suggest a positive impact on predicted CHD risk in severely obese patients. Long-term studies are needed to confirm our results and to ascertain the effects on CHD risk estimates after BPD-DS surgery.     

Effect of biliopancreatic diversion on hypertension in severely obese patients.

Hypertension is a medical disorder frequently associated with severe obesity, and the effect of weight loss on the reduction of blood pressure has been well established. In this study, the relationships between the weight loss surgically obtained by biliopancreatic diversion and blood pressure were investigated in a population of severely obese patients with preoperative hypertension. At 1 year following the operation, blood pressure was normalized in more than half of patients; in a further 10% of cases the hypertensive status resolved within the 3-year follow-up period. The resolution of hypertension was independently associated with age and body weight and was unrelated to sex, the amount of weight loss, or body fat distribution. In severely obese patients with hypertension undergoing bariatric surgery, biliopancreatic diversion is advisable since it achieves and supports the maintenance of body weight close to the ideal value.     

Body composition in Chinese subjects: relationship with age and disease

Body composition measurement by dual energy absorptiometry was carried out in 160 men (age 45-87 years) and 407 women (age 20-88 years) consisting of volunteers and 25 men and 14 women with chronic obstructive airways disease (COAD) not receiving steroids from a hospital respiratory clinic. The objectives of this study were to provide normal reference values for adult Chinese including the elderly; to examine the effect of age and COAD on body composition; and to compare the use of body mass index (BMI) as a measure of obesity or malnutrition compared with body composition measurements. Values for body composition were different when compared with studies in the Caucasian population. In both sexes, height and lean mass decreased in a linear fashion with aging. In men, total body water increased till the 55-65 age group and then decreased. In women, total body water and bone mineral content also decreased with aging in a linear fashion. Changes in weight, BMI, fat mass and percentage fat with aging were also present in women and followed a quadratic trend. BMI was not a sensitive index of obesity or undernutrition, having approximately only 50-60% sensitivity in detecting high percentage fat or low standardised lean mass values. COAD was associated with low BMI only. Body composition measurements changes with aging, and should be used instead of BMI as a better indication of obesity or undernutrition. Reference values derived from the appropriate ethnic group should be used.     

Body composition in Chinese subjects: relationship with age and disease

Body composition measurement by dual energy absorptiometry was carried out in 160 men (age 45–87 years) and 407 women (age 20–88 years) consisting of volunteers and 25 men and 14 women with chronic obstructive airways disease (COAD) not receiving steroids from a hospital respiratory clinic. The objectives of this study were to provide normal reference values for adult Chinese including the elderly; to examine the effect of age and COAD on body composition; and to compare the use of body mass index (BMI) as a measure of obesity or malnutrition compared with body composition measurements. Values for body composition were different when compared with studies in the Caucasian population. In both sexes, height and lean mass decreased in a linear fashion with aging. In men, total body water increased till the 55–65 age group and then decreased. In women, total body water and bone mineral content also decreased with aging in a linear fashion. Changes in weight, BMI, fat mass and percentage fat with aging were also present in women and followed a quadratic trend. BMI was not a sensitive index of obesity or undernutrition, having approximately only 50–60% sensitivity in detecting high percentage fat or low standardised lean mass values. COAD was associated with low BMI only. Body composition measurements changes with aging, and should be used instead of BMI as a better indication of obesity or undernutrition. Reference values derived from the appropriate ethnic group should be used.     

Body composition analysis and changes in airways function in obese adults after hypocaloric diet

STUDY OBJECTIVES: To determine the relationship between weight-loss and pulmonary function indexes, focusing on forced expiratory flows (ie, FEV(1), forced expiratory flow at 50% of vital capacity [FEF(50)], forced expiratory flow at 75% of vital capacity, and forced expiratory flow at 25 to 75% of vital capacity [FEF(25--75)]). Specifically, to determine the effect of losses in total and segmental fat mass (FM) and of modifications in lean body mass, after restricted hypocaloric diet, on pulmonary function among obese adults. DESIGN: Cross-sectional, observational. SETTINGS: Human Physiology Division, Faculty of Medicine and Surgery, "Tor Vergata" University, Rome, Italy. PATIENTS: Thirty obese adults (mean [+/- SD] baseline body mass index [BMI], 32.25 +/- 3.99 kg/m(2)), without significant obstructive airway disease, were selected from among participants in a weight-loss program. MEASUREMENTS AND RESULTS: Anthropometric, body composition (BC), and respiratory parameters of all participants were measured before and after weight loss. Total and segmental lean body and FM were obtained by dual-energy x-ray absorptiometry. Dynamic spirometric tests and maximum voluntary ventilation (MVV) were performed. The BC parameters (ie, body weight [BW], BMI, the sum skinfold thicknesses, thoracic inhalation circumference, thoracic expiration circumference, total FM, and trunk FM [FMtrunk]) were significantly decreased (p < or = .0001) after a hypocaloric diet. The mean vital capacity, FEV(1), FEF(50), FEF(25-75), expiratory reserve volume, and MVV significantly increased (p < or = 0.05) with weight loss. The correlation coefficient for Delta FEF(25--75) (r = 0.20) was numerically higher than Delta FEF(50) and Delta FEV(1) (r = 0.14 and r = 0.08, respectively) for the BW loss. Moreover, the correlation coefficient for Delta FEF(25--75) (r = 0.45) was significantly higher (p < or = 0.02) than those for Delta FEF(50) and Delta FEV(1) (r = 0.38 and r = 0.15, respectively) for FMtrunk loss. CONCLUSIONS: This study shows that a decrease in total and upper body fat obtained by restricted diet was not accompanied by a decrease in ventilatory muscle mass. FMtrunk loss was found to have improved airflow limitation, which can be correlated to peripheral airways function.     

Pulmonary function and energy expenditure after marked weight loss in obese women: observations before and one year after gastric banding

Pulmonary function and pulmonary gas exchange at rest, and during and after a standard exercise load of 500 kpm in 1 min on bicycle ergometer were studied in 34 women with severe, uncomplicated obesity, aged 37.8 (20-59) years, before and 1 year after gastric banding, resulting in a weight loss from 113.2 (84-156) to 81.7 (60-110) kg. Following the weight loss, TLC and VC rose from 93 and 94 per cent of expected to 98 and 101 per cent, respectively. FRC, ERV and FRC/TLC rose more markedly from 77, 64 and 83 per cent to 98, 109 and 99 per cent. IC fell from 108 to 99 per cent. RV and RV/TLV remained unchanged. FEV1.0 rose from 97 to 103 per cent, while MVV rose from 102 to 112 per cent, i.e. above normal. TLCO and PaCO2 remained unchanged, at 90 and 95 per cent, whereas PaO2 rose from 86 to 91 per cent. Resting O2 intake (VO2) decreased from 147 to 115 per cent of the expected for normal weight women, while VO2/BSA decreased from 113 to 99 per cent, the changes being greater than expected from commonly used formulas for prediction of metabolic rate. O2 cost of work (EO2) decreased from 142 to 105 per cent. Resting ventilation (V) declined from 136 to 113 per cent, while ventilatory cost of work (EV) decreased from 142 to 105 per cent. CO2 recovery time after work (CO2RT) decreased from 121 to 100 per cent, while the ratios CO2RT to EO2 and to extra CO2 output of work (ECO2) rose slightly. Thus, the loss of weight led to increased filling of the lungs, improved dynamic function, reduced ventilation/perfusion disturbances and greater than expected reduction of energy expenditure, both at rest and exercise. In the obese state there was no evidence of alveolar hypoventilation or impaired ventilatory control. The beneficial effect of weight reduction on the exertional dyspnea included a combination of marked reduction of ventilatory demands and moderate rise in ventilatory capacity.     

Gastric histomorphology and secretory biochemistry after biliopancreatic diversion

When paired data are considered and unpaired results are compared with controls, it appears that no significant changes of gastric histomorphology occur following biliopancreatic diversion.     

The effect of sibutramine on energy expenditure and body composition in obese adolescents

CONTEXT: Childhood obesity is now considered to be an epidemic. Drug therapy in this age group remains a topic of research. OBJECTIVE: The objective of this study was to examine the effect of treatment with sibutramine (10 mg) on body composition and energy expenditure in obese adolescents. DESIGN: The study was conducted as a randomized, double-blind, placebo-controlled trial. SETTING: The study was set in an obesity research center. PATIENTS: The patients were 24 obese adolescents (age 12-17 yr, 11 boys); four patients withdrew. INTERVENTION: Intervention was sibutramine (Meridia) or placebo in combination with an energy-restricted diet and exercise plan for 12 wk, followed by an identical, but medication-free, treatment period (follow-up). MAIN OUTCOME MEASURE: Change in body mass index (BMI) sd score (BMI-SDS) was the principal measure of efficacy. Body composition and total energy expenditure were measured by stable isotopes and further calculated according to the four-component model, using underwater weighing and dual x-ray absorptiometry. Basal metabolic rate (BMR) was measured by ventilated hood and adjusted for sex and body composition (BMRadj). RESULTS: After intervention, the decrease in BMI-SDS was comparable in both groups. During follow-up, BMI further decreased in the placebo group but stabilized in the sibutramine group. Changes in the percentage of fat mass were not different between both groups. BMRadj decreased in the placebo group and remained constant in the sibutramine group. During follow-up, BMRadj decreased in the sibutramine group and increased in the placebo group. Changes in total energy expenditure were not significantly different. CONCLUSION: The effect of sibutramine on BMI-SDS was not significant. Sibutramine may diminish the decrease in BMRadj associated with energy restriction in obese adolescents.     

Long-term effect of biliopancreatic diversion on blood pressure in hypertensive obese patients

BACKGROUND: The weight loss surgically induced by gastroplasty or gastric banding has only a transitory effect on the arterial hypertension of the severely obese patients, and a prevalence of hypertension similar to that of controls has been reported 8 years after the operation. METHODS: We studied the effects of biliopancreatic diversion in a series of 73 severely obese patients with preoperative hypertension throughout a 10-year follow-up period. Body weight dropped from 135.5 kg to 84.8 kg and remained substantially unchanged during the entire 10-year period, hypertension resolved in 41 subjects within the first postoperative year and the resolution rate increased slightly and progressively with time: at 10 years only 15 subjects were still hypertensive. Mean systolic and diastolic blood pressure (BP) value decreased within the first postoperative year as well as the pulse pressure (mean +/- standard deviation from 168 +/- 25 to 143 +/- 22 mm Hg, from 105 +/- 18 to 88 +/- 13 mm Hg, and from 65 +/- 16 to 50 +/- 13 mm Hg, respectively) and remained essentially unchanged throughout all the follow-up; 10 years after surgery the systolic BP and pulse pressure values (127 +/- 14 mm Hg and 42 +/- 6 mm Hg, respectively) were significantly lower than those observed at shorter term. CONCLUSIONS: In severely obese patients with arterial hypertension, the weight loss determined by biliopancreatic diversion in most cases is accompanied by the normalization of BP, which remains into physiological range until very long term.     

Steatohepatitis and fatal hepatic failure after biliopancreatic diversion.

Steatohepatitis and hepatic failure are well known complications of jejunoileal bypass, an operation that has been abandoned as a treatment for severe obesity because of its potential for adverse metabolic consequences. Biliopancreatic diversion is a novel operation designed to avoid the harmful effects of jejunoileal bypass. Although it has not gained wide acceptance, this procedure is being advocated by some surgeons as a safe and effective treatment for severe obesity. Published reports indicate that liver histology generally remains stable or improves after biliopancreatic diversion. We present a patient who developed steatohepatitis and subsequently died in hepatic failure after this operation. Severe liver disease should be added to the list of complications that may follow biliopancreatic diversion.     

Effects of the biliopancreatic diversion on energy balance in the rat

OBJECTIVE: This study was carried out to determine the effects of the biliopancreatic diversion (BPD), a bariatric surgery applied to the treatment of morbidly obese humans, on energy balance in rats. METHODS: BPD was performed on a group of male Wistar rats. Body weight and food intake were measured daily throughout the study. Feces were also collected to assess energy losses and the determination of digestible energy. Energy expenditure and body composition were also determined for the 50-day length of the protocol. On the day of killing, the brain, the entire intestinal tract and white and brown adipose tissues were collected and weighed. Expression of neuropeptide Y (NPY) and agouti-related protein (AgRP) in the ARC nucleus were assessed by in situ hybridization. RESULTS: Marked changes in the regulation of energy balance were observed in the BPD-operated rats. A decrease in digestible energy and food intake coupled with an increase in the fecal energy density and protein fecal energy led to an important weight loss in the BPD-operated rats. This weight loss was observed in the loss of fat mass (specifically the white epididymal, inguinal, retroperitoneal and brown adipose tissues). The rats modified their food intake pattern to be able to potentially eat more during the entire day. An increase in the surfaces of all intestinal structures (muscular and mucosal layers) was observed in the BPD-operated rats. The NPY and AgRP expression in the brain were both shown to be greater in the BPD-operated rats than in the control animals. At the beginning of the study, the surgery led to an energy expenditure decrease, which, however, did not persist throughout the study despite the fact that BPD-operated rats exhibited persistent lower fat free masses. CONCLUSION: BPD led to a noticeable reduction in weight and fat gains in rats, which was in large part owing to a decrease in digestible energy intake led to by the gastrectomy, the intestinal malabsorption inherent to the surgery and to potentially a thermogenesis stimulation that occurred in the second end of the study. The reduction in energy gain occurs despite adaptations to thwart the intestinal malabsorption and the hunger signals from the central nervous system.     

Glucose-induced sympathetic activity and energy expenditure during acute alpha2-adrenergic antagonism in obese subjects

OBJECTIVE: To determine the effect of an alpha2-adrenoceptor antagonist, idazoxan, on the sympathetic nervous system and on energy expenditure responses after an oral glucose load, in obese patients. (idazoxan acts as an indirect sympathomimetic drug through blockade of presynaptic alpha2-adrenoceptors). DESIGN: Double-blind randomized placebo-controlled cross-over study. Idazoxan (40 mg) or placebo were administered orally 90 min before a 100 g oral glucose load. SUBJECTS: Twelve long-standing obese subjects (six men and six women, age range from 24 to 45 y, body mass index range from 30.2 to 41.3 kg/m2). MEASUREMENTS: Energy expenditure was derived from oxygen consumption and carbon dioxide production according to indirect calorimetry. Plasma samples were obtained for plasma adrenaline and noradrenaline, glucose, non-esterified fatty acid (NEFA), glycerol and insulin determinations. RESULTS: The plasma noradrenaline concentration response to the glucose load was significantly higher after idazoxan than after placebo administration. The time-course of glucose load-induced thermogenesis was not significantly different after administration of idazoxan nor placebo. Idazoxan administration did not modify the insulin, non-esterified fatty acids or glycerol concentration responses to the glucose load. Neither heart rate nor blood pressure values were modified by idazoxan when compared to placebo. However, idazoxan significantly improved glucose tolerance. CONCLUSION: The alpha2-adrenergic antagonist idazoxan increases glucose-induced sympathetic activity but not energy expenditure in obese subjects. These data do not argue for the development of alpha2AR antagonist compounds as anti-obesity treatment.     

Portomesenteric venous thrombosis:An early postoperative complication after laparoscopic biliopancreatic diversion

The number of bariatric operations,as well as the incidence of perioperative complications,has risen sharply in the past ten years.Perioperative acute portal vein thrombosis is an infrequent and potentially severe postoperative complication that has not yet been reported after biliopancreatic diversion(BPD).Three cases are presented of portal vein thrombosis that occurred following BPD treatment for morbid obesity and type 2 diabetes.The thromboses were detectedby abdominal ultrasound and computed tomography with intravenous contrast.The portomesenteric venous thromboses in all three cases presented as unexpected abdominal pain several days after discharge from the hospital.The complications occurred despite adequate perioperative prophylaxis and progressed to bowel gangrene in the diabetic patients only.These cases demonstrate the occurrence of this rare type of complication,which may be observed by physicians that do not routinely treat bariatric patients.Awareness of this surgical complication will allow for early diagnosis and prompt initiation of adequate therapy.