Neutrophil Activation in Morbid Obesity,Chronic Activation of Acute Inflammation

Recent studies show that morbid obesity is associated with activation of the innate immune response. Neutrophil activation is a fundamental process in the innate immune response. Therefore, the activation state of neutrophils in severely obese subjects and the effect of bariatric surgery on neutrophil activation was evaluated. Neutrophil activation was assessed by measuring circulating concentrations of myeloperoxidase (MPO) and calprotectin in 37 severely obese and 9 control subjects (enzyme‐linked immunosorbent assay). Moreover, membrane expression of CD66b on circulating neutrophils was measured using flow cytometry in a group of seven severely obese and six control subjects. Immunohistochemical detection of MPO was performed in adipose and muscle tissue. Plasma MPO and calprotectin levels were significantly increased in severely obese subjects as compared to healthy controls, 27.1 ± 10.8 vs. 17.3 ± 5.5 ng/ml (P < 0.001) and 115.5 ± 43.5 vs. 65.1 ± 23.1 ng/ml (P < 0.001) for MPO and calprotectin, respectively. In line, CD66b expression was significantly increased in severely obese individuals, 177.3 ± 43.7 vs. 129.7 ± 9.2 (mean fluorescence intensity) (P < 0.01). Bariatric surgery resulted in decreased calprotectin, but MPO plasma levels remained elevated. Adipose and muscle tissue did not contain increased numbers of MPO expressing cells in severely obese individuals. These results point out that circulating neutrophils are activated to a greater extent in severely obese subjects. Our data support the finding that the innate immune system is activated in severely obese individuals. Moreover, because neutrophils have a short life span, this indicates that the chronic inflammatory condition associated with morbid obesity is characterized by a continuous activation of the innate immune system.     

Resting Metabolic Rate in Severely Obese Diabetic and Nondiabetic Subjects

Objectives : To compare the resting metabolic rate (RMR) between diabetic and nondiabetic obese subjects and to develop a predictive equation of RMR for these subjects. Research Methods and Procedures : Obese adults (1088; mean age = 44.9 ± 12.7 years) with BMI ≥ 35 kg/m² (mean BMI = 46.4 ± 8.4 kg/m²) were recruited. One hundred forty‐two subjects (61 men, 81 women) were diagnosed with type 2 diabetes (DM), giving the prevalence of DM in this clinic population as 13.7%. RMR was measured by indirect calorimetry, and several multivariate linear regression models were performed using age, gender, weight, height, BMI, fat mass, fat mass percentage, and fat‐free mass as independent variables. Results : The severely obese patients with DM had consistently higher RMR after adjustment for all other variables. The best predictive equation for the severely obese was RMR = 71.767 ? 2.337 × age + 257.293 × gender (women = 0 and men = 1) + 9.996 × weight (in kilograms) + 4.132 × height (in centimeters) + 145.959 × DM (nondiabetic = 0 and diabetic = 1). The age, weight, and height‐adjusted least square means of RMR between diabetic and nondiabetic groups were significantly different in both genders. Discussion : Severely obese patients with type 2 diabetes had higher RMR than those without diabetes. The RMR of severely obese subjects was best predicted by an equation using age, gender, weight, height, and DM as variables.     

Adapted Changes in Left Ventricular Structure and Function in Severe Uncomplicated Obesity

Objective: A massive amount of fat tissue, as that observed in obese subjects with BMI over 50 kg/m², could affect cardiac morphology and performance, but few data on this issue are available. We sought to evaluate cardiac structure and function in uncomplicated severely obese subjects. Research Methods and Procedures: We studied 55 uncomplicated severely obese patients, 40 women, 15 men, mean age 35.5 ± 10.2 years, BMI 51.2 ± 8.8 kg/m², range 43 to 81 kg/m², with a history of fat excess of at least 10 years, and 55 age‐matched normal‐weight subjects (40 women, 15 men, mean BMI 23.8 ± 1.2 kg/m²) as a control group. Each subject underwent an echocardiogram to evaluate left ventricular (LV) mass and geometry and systolic and diastolic function. Results: Severely obese subjects showed greater LV mass and indexed LV mass than normal‐weight subjects (p < 0.01 for all parameters). Nevertheless, LV mass was appropriate for sex, height^2.7, and stroke work in most (77%) uncomplicated severely obese subjects. In addition, no significant difference in LV mass indices and LV mass appropriateness between obese subjects with BMI ≥ 50 kg/m² and those with BMI ≤ 50 kg/m² was found. Obese subjects also showed higher ejection fraction and midwall shortening than normal‐weight subjects (p = 0.05 and p < 0.01, respectively), suggesting a hyperdynamic systolic function. No significant difference in systolic performance between obese subjects with BMI ≥ 50 kg/m² and those with BMI ≤ 50 kg/m² was seen. Discussion: Our data show that uncomplicated severe obesity, despite the massive fat tissue amount, is associated largely with adapted and appropriate changes in cardiac structure and function.     

Quality of Life after Lap‐Band Placement: Influence of Time,Weight Loss,and Comorbidities

Objective: To assess the quality of life (QOL) in severely obese subjects before and after Lap‐Band gastric restrictive surgery and identify factors that may influence change. Research Methods and Procedures: All patients, over a 3‐year period, attending for preoperative assessment (n = 459) or annual review after surgery (n = 641) have completed the Short Form‐36 (SF‐36) health survey. Eight domain and physical component summary (PCS) and mental component summary (MCS) scores were calculated. Scores were analyzed in groups based on time after surgery and compared with community normal (CN) values. Paired preoperative and 1‐year scores (n = 218) data were used to find predictors of QOL change. Results: All preoperative mean scores (n = 459) were lower than CN values, with greater impairment in the PCS (36.8 ± 9.5 vs. CN: 51.3 ± 8.3, p < 0.001) than in the MCS (45.7 ± 8.2 vs. CN: 48.8 ± 9.5, p < 0.001) scores. After 1 year, scores were closer to CN scores (PCS: 52.4 ± 8.2 and MCS: 48.4 ± 7.7), and these remained closer for 4 years. Preoperative obesity comorbidity, especially physical disability, was the best predictor of poor preoperative SF‐36 scores and of improvement in scores at 1 year. The percentage of excess weight loss at 1 year (46 ± 16%) was of little predictive value of improved QOL. Discussion: Severely obese subjects have poor health‐related QOL as measured by the SF‐36 health survey. Lap‐Band surgery for this group has provided a dramatic and sustained improvement in all measures of the SF‐36. Improvement is greater in those with greater preoperative disability, and the extent of weight loss is not a good predictor of improved QOL.     

Cost‐Effectiveness of a Low‐Carbohydrate Diet and a Standard Diet in Severe Obesity

Objective: Low‐carbohydrate diets have become a popular alternative to standard diets for weight loss. Our aim was to compare the cost‐effectiveness of these two diets. Research Methods and Procedures: The patient population included 129 severely obese subjects (BMI = 42.9) from a randomized trial; participants had a high prevalence of diabetes or metabolic syndrome. We compared within‐trial costs, quality‐adjusted life years (QALYs), and the incremental cost‐effectiveness ratio (CER) for the two study groups. We imputed missing values for QALYs. The CER was bootstrapped to derive 95% confidence intervals and to define acceptability cut‐offs. We took a societal perspective for our analysis. Results: Total costs during the one year of the trial were $6742 ± 6675 and $6249 ± 5100 for the low‐carbohydrate and standard groups, respectively (p = 0.78). Participants experienced 0.64 ± 0.02 and 0.61 ± 0.02 QALYs during the one year of the study, respectively (p = 0.17 for difference). The point estimate of the incremental CER was $?1225/QALY (i.e., the low‐carbohydrate diet dominated the standard diet). However, in the bootstrap analysis, the wide spread of CERs caused the 95% confidence interval to be undefined. The probabilities that the low‐carbohydrate diet was acceptable, using cut‐offs of $50, 000/QALY, $100, 000/QALY, and $150, 000/QALY, were 72.4% 78.6%, and 79.8%, respectively. Discussion: The low‐carbohydrate diet was not more cost‐effective for weight loss than the standard diet in the patient population studied. Larger studies are needed to better assess the cost‐effectiveness of dietary therapies for weight loss.     

BMI,Physical Activity,and Health Care Utilization/Costs among Medicare Retirees

Objective: To examine the influence of physical activity (PA) and BMI on health care utilization and costs among Medicare retirees. Research Methods and Procedures: This cross‐sectional study was based on 42, 520 Medicare retirees in a U.S.‐wide manufacturing corporation who participated in indemnity/perferred provider and one health risk appraisal during the years 2001 and 2002. Participants were assigned into one of the three weight groups: normal weight, overweight, and obese. PA behavior was classified into three levels: sedentary (0 time/wk), moderately active (1 to 3 times/wk), and very active (4+ times/wk). Results: Generalized linear models revealed that the moderately active retirees had $1456, $1731, and $1177 lower total health care charges than their sedentary counterparts in the normal‐weight, overweight, and obese groups, respectively (p < 0.01). The very active retirees had $1823, $581, and $1379 lower costs than the moderately active retirees. Health care utilization and specific costs showed similar trends with PA levels for all BMI groups. The total health care charges were lower with higher PA level for all age groups (p < 0.01). Discussion: Regular PA has strong dose‐response effects on both health care utilization and costs for overweight/obese as well as normal‐weight people. Promoting active lifestyle in this Medicare population, especially overweight and obese groups, could potentially improve their well‐being and save a substantial amount of health care expenditures. Because those Medicare retirees are hard to reach in general, more creative approaches should be launched to address their needs and interests as well as help reduce the usage of health care system.     

Health Outcomes of Gastric Bypass Patients Compared to Nonsurgical,Nonintervened Severely Obese

Favorable health outcomes at 2 years postbariatric surgery have been reported. With exception of the Swedish Obesity Subjects (SOS) study, these studies have been surgical case series, comparison of surgery types, or surgery patients compared to subjects enrolled in planned nonsurgical intervention. This study measured gastric bypass effectiveness when compared to two separate severely obese groups not participating in designed weight‐loss intervention. Three groups of severely obese subjects (N = 1,156, BMI ≥ 35 kg/m²) were studied: gastric bypass subjects (n = 420), subjects seeking gastric bypass but did not have surgery (n = 415), and population‐based subjects not seeking surgery (n = 321). Participants were studied at baseline and 2 years. Quantitative outcome measures as well as prevalence, incidence, and resolution rates of categorical health outcome variables were determined. All quantitative variables (BMI, blood pressure, lipids, diabetes‐related variables, resting metabolic rate (RMR), sleep apnea, and health‐related quality of life) improved significantly in the gastric bypass group compared with each comparative group (all P < 0.0001, except for diastolic blood pressure and the short form (SF‐36) health survey mental component score at P < 0.01). Diabetes, dyslipidemia, and hypertension resolved much more frequently in the gastric bypass group than in the comparative groups (all P < 0.001). In the surgical group, beneficial changes of almost all quantitative variables correlated significantly with the decrease in BMI. We conclude that Roux‐en‐Y gastric bypass surgery when compared to severely obese groups not enrolled in planned weight‐loss intervention was highly effective for weight loss, improved health‐related quality of life, and resolution of major obesity‐associated complications measured at 2 years.     

Increase in visfatin after weight loss induced by gastroplastic surgery

Objective: The recently described adipokine visfatin is produced in visceral fat and has been suggested to influence insulin resistance. To investigate whether visfatin concentrations are related to changes in body weight, this adipokine was measured in insulin‐resistant severely obese patients before and after gastroplastic surgery. Research Methods and Procedures: Visfatin, interleukin‐6, high‐sensitivity C‐reactive protein, homeostasis model assessment of insulin resistance (HOMA‐IR), and other clinical parameters were assessed in 36 severely obese subjects (28 female; mean age, 43 years) with a median BMI of 44.3 kg/m² (95% confidence interval, 43.3 to 48.1 kg/m²). Results: After surgery, BMI decreased to a median of 31.9 kg/m² (30.1 to 35.1 kg/m²) (p < 0.0001). Median visfatin concentrations increased significantly after weight loss [70.9 ng/mL (61.4 to 75.6 ng/mL) vs. 86.4 ng/mL (79.4 to 89.8 ng/mL); p < 0.0005]. This increase correlated with the decrease of insulin and HOMA‐IR and was associated with a reduction in plasma interleukin‐6 and high‐sensitivity C‐reactive protein concentrations. Discussion: Massive weight loss after gastroplastic surgery is accompanied by an increase in circulating concentrations of the novel adipokine visfatin. This increase correlates with the decrease in plasma insulin concentrations and HOMA‐IR.     

Obesity and Medicare Expenditure: Accounting for Age‐Related Height Loss

To determine the relationship between BMI and Medicare expenditure for adults 65‐years and older and determine whether this relationship changes after accounting for misclassification due to age‐related height loss. Using a cross sectional study design, the relationship between BMI and fee‐for‐service Medicare expenditure was examined among beneficiaries who completed the Medicare Current Beneficiary Survey (MCBS) in 2002, were not enrolled in Medicare Health Maintenance Organization, had a self‐reported height and weight, and were 65 and older (n = 7,706). Subjects were classified as underweight, normal weight, overweight, obese (obese I), and severely obese (obese II/III). To adjust BMI for the artifactual increase associated with age‐related height loss, the reported height was transformed by adding the sex‐specific age‐associated height loss to the reported height in MCBS. The main outcome variable was total Medicare expenditure. There was a significant U‐shaped pattern between unadjusted BMI and Medicare expenditure: underweight $4,581 (P < 0.0003), normal weight $3,744 (P < 0.0000), overweight $3,115 (reference), obese I $3,686 (P < 0.0039), and obese II/III $4,386 (P < 0.0000). This pattern persisted after accounting for height loss: underweight $4,640 (P < 0.0000), normal weight $3,451 (P < 0.0507), overweight $3,165 (reference), obese I $3,915 (P < 0.0010), and obese II/III $4,385 (P < 0.0004) compared to overweight. In older adults, minimal cost is not found at “normal” BMI, but rather in overweight subjects with higher spending in the obese and underweight categories. Adjusting for loss‐of‐height with aging had little affect on cost estimates.     

Effort‐Related Calf Pain in the Obese and Long‐Term Changes after Surgical Obesity Treatment**

Objective: To compare the prevalence of effort‐related calf pain in an obese and a general population and to analyze the incidence of and recovery from such pain after surgical and conventional obesity treatment. Research Methods and Procedures: A random sample of 1135 subjects from a general population was compared with 6328 obese subjects in the Swedish Obese Subjects study. Obese subjects were followed longitudinally, and information about calf pain was obtained from surgically and conventionally treated patients for up to 6 years. Results: In both sexes, self‐reported calf pain was more common in the obese than in the general population [odds ratios (ORs) 5.0 and 4.0 in men and women, respectively, p < 0.001]. Obese patients undergoing surgery had a lower 6‐year incidence of calf pain compared with the conventionally treated control group (ORs 0.39 and 0.61, p < 0.05). Among subjects reporting symptoms at baseline, the 6‐year recovery rate was higher in the surgical group compared with the control group (ORs 15.3 and 5.9, p < 0.001). Discussion: Obese subjects have markedly more problems with effort‐related calf pain than the general population. Surgical obesity treatment reduces the long‐term risk of developing claudication symptoms and increases the likelihood of recovering from such symptoms.     

Cancer Incidence and Mortality After Gastric Bypass Surgery

Despite weight loss recommendations to prevent cancer, cancer outcome studies after intentional weight loss are limited. Recently, reduced cancer mortality following bariatric surgery has been reported. This study tested whether reduced cancer mortality following gastric bypass was due to decreased incidence. Cancer incidence and mortality data through 2007 from the Utah Cancer Registry (UCR) were compared between 6,596 Utah patients who had gastric bypass (1984–2002) and 9,442 severely obese persons who had applied for Utah Driver's Licenses (1984–2002). Study outcomes included incidence, case‐fatality, and mortality for cancer by site and stage at diagnosis of all gastric bypass patients, compared to nonoperated severely obese controls. Follow‐up was over a 24‐year period (mean 12.5 years). Total cancer incidence was significantly lower in the surgical group compared to controls (hazard ratio (HR) = 0.76; confidence interval (CI) 95%, 0.65–0.89; P = 0.0006). Lower incidence in surgery patients vs. controls was primarily due to decreased incidence of cancer diagnosed at regional or distant stages. Cancer mortality was 46% lower in the surgery group compared to controls (HR = 0.54; CI 95%, 0.37–0.78; P = 0.001). Although the apparent protective effect of surgery on risk of developing cancer was limited to cancers likely known to be obesity related, the inverse association for mortality was seen for all cancers. Significant reduction in total cancer mortality in gastric bypass patients compared with severely obese controls was associated with decreased incidence, primarily among subjects with advanced cancers. These findings suggest gastric bypass results in lower cancer risk, presumably related to weight loss, supporting recommendations for reducing weight to lower cancer risk.     

A Rare Variant in the Visfatin Gene (NAMPT/PBEF1) Is Associated With Protection From Obesity

Visfatin was recently reported as a novel adipokine encoded by the NAMPT (PBEF1) gene. This study was aimed at investigation of the possibility that single‐nucleotide polymorphisms (SNPs) in the visfatin gene are associated with either obesity or type 2 diabetes (T2D). A set of eight “tag‐SNPs” were selected and ABI SNPlex assays designed for genotyping purposes. A total of 1,709 severely obese subjects were typed (896 class III obese adults and 813 children) together with 2,367 T2D individuals and 2,850 controls. For quantitative trait analysis, an additional 2,362 subjects were typed for rs10487818 from a general population sample. One rare SNP, rs10487818, located in intron 4 of NAMPT was associated with severe obesity, with a minor allele frequency of 1.6% in controls, 0.4% in the class III obese adults and, remarkably, 0% in the severely obese children. A highly significant association was observed for the presence or absence of the rare allele, i.e., (A,A) vs. (A,T + T,T) genotypes, in children (P = 6 × 10^?9) and in adults (P = 8 × 10^?5). No other significant (P < 0.05) association was observed with obesity or T2D for this or any other SNP. No association with BMI or waist‐to‐hip ratio was observed in a general population sample (n = 5,212). This is one of the first rare SNPs shown to be protective against a common polygenic disease and provides further evidence that rare alleles of strong effect can contribute to complex diseases such as severe obesity.     

Structural and Functional Alterations of Subcutaneous Small Resistance Arteries in Severe Human Obesity

Obese persons are at increased cardiovascular risk and exhibit increased arterial stiffness and impaired endothelial function of large‐ and medium‐size arteries. We hypothesized that normotensive subjects suffering from severe obesity would also present remodeling and endothelial dysfunction of small resistance arteries. A total of 16 lean (age: 49.6 ± 2.9 years, BMI: 22.9 ± 0.3 kg/m², mean ± s.e.m.) and 17 age‐matched severely obese (BMI: 41.1 ± 2.3 kg/m²) normotensive subjects were investigated. None had glucose or lipid metabolic abnormalities except for insulin resistance. Resistance arteries, dissected from abdominal subcutaneous tissue, were assessed on a pressurized myograph. For superimposable blood pressure, the media thickness, media cross‐sectional area (CSA), and media‐to‐lumen ratio values of resistance arteries were markedly and significantly greater in obese compared to lean subjects (media thickness 26.3 ± 0.6 vs. 16.2 ± 0.6 µm, CSA 22,272 ± 1,339 vs. 15,183 ± 1,186 µm², and media‐to‐lumen ratio 0.113 ± 0.006 vs. 0.059 ± 0.001, respectively, P < 0.01). Acetylcholine‐induced relaxation was impaired in vessels from obese subjects compared to the lean individuals (?40.4 ± 1.3%, P < 0.01), whereas endothelium‐independent vasorelaxation was similar in all groups. Stiffness of small arteries as assessed by the stress/strain relationship was similar in lean and severely obese subjects. We conclude that severe human obesity is associated with profound alterations in structural and functional characteristics of small arteries, which may be responsible for the presence of elevated cardiovascular risk and increased incidence of coronary, cerebrovascular and renal events reported in obesity.     

Insulin Resistance in Nondiabetic Morbidly Obese Patients: Effect of Bariatric Surgery

Objective: To evaluate insulin action on substrate use and insulinemia in nondiabetic class III obese patients before and after weight loss induced by bariatric surgery. Research Methods and Procedures: Thirteen obese patients (four men/nine women; BMI = 56.3 ± 2.7 kg/m²) and 13 lean subjects (five men/eight women; BMI = 22.4 ± 0.5 kg/m²) underwent euglycemic clamp, oral glucose tolerance test, and indirect calorimetry. The study was carried out before (Study I) and after (～40% relative to initial body weight; Study II) weight loss induced by Roux‐en‐Y Gastric bypass with silastic ring surgery. Results: The obese patients were insulin resistant (whole‐body glucose use = 19.7 ± 1.5 vs. 51.5 ± 2.4 μmol/min per kilogram fat‐free mass, p < 0.0001) and hyperinsulinemic in the fasting state (332 ± 86 vs. 85 ± 5 pM, p < 0.0001) and during the oral glucose tolerance test compared with the lean subjects. Fasting plasma insulin normalized after weight loss, whereas whole‐body glucose use increased (35.5 ± 3.7 μmol/min per kilogram fat‐free mass, p < 0.05 vs. Study I). The higher insulin clearance of obese did not change during the follow‐up period. Insulin‐induced glucose oxidation and nonoxidative glucose disposal were lower in the obese compared with the lean group (all p < 0.05). In Study II, the former increased slightly, whereas nonoxidative glucose disposal reached values similar to those of the control group. Fasting lipid oxidation was higher in the obese than in the control group and did not change significantly in Study II. The insulin effect on lipid oxidation was slightly improved (p = 0.01 vs. Study I). Discussion: The rapid weight loss after surgery in obese class III patients normalized insulinemia and improved insulin sensitivity almost entirely due to glucose storage, whereas fasting lipid oxidation remained high.     

Plasma Adiponectin Increases Postprandially in Obese,but not in Lean,Subjects

Objective: We investigated the acute responses of plasma adiponectin levels to a test meal in lean and obese subjects. Research Methods and Procedures: We studied 13 lean and 11 obese subjects after a 10‐hour overnight fast. Glucose, insulin, and adiponectin concentrations were measured at baseline and 15, 30, 60, 120, and 180 minutes after a fixed breakfast. Results: At baseline, fasting adiponectin concentrations were lower in the obese group vs. the lean group [mean (95% confidence interval): 2.9 (2.1 to 4.1) μg/mL vs. 8.6 (6.5 to 11.3) μg/mL], but rose 4‐fold postprandially in the obese group, reaching a peak at 60 minutes [baseline: 2.9 (2.1 to 4.1) μg/mL vs. 60 minutes: 12.1 (8.5 to 17.4) μg/mL; p< 0.0001] and remaining elevated for the remainder of the study. There were no postprandial changes in plasma adiponectin concentrations in lean subjects. Discussion: This increase of adiponectin concentrations in obese individuals might have important beneficial effects on postprandial glucose and lipid metabolism and might be viewed as a mechanism for maintaining normal glucose tolerance in those who are obese and insulin resistant.     

Fat Overload Induces Changes in Circulating Lactoferrin That Are Associated With Postprandial Lipemia and Oxidative Stress in Severely Obese Subjects

Lactoferrin is an innate immune system protein with anti‐inflammatory and antioxidant activities. We aimed to evaluate circulating lactoferrin levels in association with lipid concentrations, and parameters of oxidative stress and inflammation in subjects with morbid obesity after an acute fat intake. The effects of a 60 g fat overload on circulating lactoferrin and antioxidant activities were evaluated in 45 severely obese patients (15 men and 30 women, BMI 53.4 ± 7.2 kg/m²). The change in circulating lactoferrin after fat overload was significantly and inversely associated with the free fatty acid (FFA) change. In those subjects with the highest increase in lactoferrin (in the highest quartile), high‐density lipoprotein (HDL)‐cholesterol decreased after fat overload to a lesser extent (P = 0.03). In parallel to lipid changes, circulating lactoferrin concentrations were inversely linked to the variations in catalase (CAT) and glutathione reductase (GSH‐Rd). Baseline circulating lactoferrin concentration was also inversely associated with the absolute change in antioxidant activity after fat overload, and with the change in C‐reactive protein (CRP). Furthermore, those subjects with higher than the median value of homeostasis model assessment of insulin secretion (HOMA_IS) had significantly increased lactoferrin concentration after fat load (885 ± 262 vs. 700 ± 286 ng/ml, P = 0.03). Finally, we further explored the action of lactoferrin in vitro. Lactoferrin (10 µmol/l) led to significantly lower triglyceride (TG) concentrations and lactate dehydrogenase activity (as expression of cell viability) in the media from adipose explants obtained from severely obese subjects. In conclusion, circulating lactoferrin concentrations, both at baseline and fat‐stimulated, were inversely associated with postprandial lipemia, and parameters of oxidative stress and fat‐induced inflammation in severely obese subjects.     

Baroreflex sensitivity in obesity: relationship with cardiac autonomic nervous system activity

Objective: The aim of this study was to test the hypothesis that baroreflex sensitivity (BRS), assessed by indirect measurement of aortic pressure, is blunted in obesity. Additionally, the potential effect of cardiac autonomic nervous system (ANS) activity, aortic compliance, and metabolic parameters on BRS of obese subjects was investigated. Research Methods and Procedures: A group of 30 women with BMI >30 kg/m² and a group of 30 controls with BMI <25 kg/m² were examined. BRS was estimated by the sequence technique, cardiac ANS activity by short‐term spectral analysis of heart rate variability (HRV), and aortic compliance by the method of applanation tonometry. Results: BRS was lower in obese women (9.18 ± 3.77 vs. 19.63 ± 9.16 ms/mm Hg, p < 0.001). The median values (interquartile range) of the power of both the high‐frequency and low‐frequency components of the HRV were higher in the lean than in the obese participants [1079.2 (202.7 to 1716.9) vs. 224.1 (72.7 to 539.6) msec², p = 0.001 and 411.8 (199.3 to 798.0) vs. 235.8 (99.4 to 424.5) msec², p = 0.01 respectively]. Low‐to‐high‐frequency ratio values were higher in the obese subjects [0.82 (0.47 to 2.1) vs. 0.57 (0.28 to 0.89), p = 0.02]. Aortic augmentation values were not significantly different between lean and obese subjects. Multivariate analysis demonstrated a significant and independent association between BRS and age (p = 0.003), BMI (p < 0.001), and high‐frequency power of HRV (p < 0.001). These variables explained 72% of the variation of BRS values. Discussion: BRS is severely reduced in obese subjects. BMI, age, and the parasympathetic nervous system activity are the main determinants of BRS. Baroreflex behavior is of clinical relevance because an attenuated BRS represents a negative prognostic factor in cardiovascular diseases, which are common in obesity.     

The effects of Goami No. 2 rice, a natural fiber-rich rice, on body weight and lipid metabolism

Objective : Increased intake of dietary fiber reduces the risk of obesity and type 2 diabetes. We assessed the effects of a fiber‐rich diet on body weight, adipokine concentrations, and the metabolism of glucose and lipids in non‐obese and obese subjects in Korea, where rice is the main source of dietary carbohydrates. Research Methods and Procedures : Eleven healthy, non‐obese and 10 obese subjects completed two 4‐week phases of individual isoenergetic food intake. During the control diet phase, subjects consumed standard rice; during the modified diet phase, subjects consumed equal proportions of fiber‐rich Goami No. 2 rice and standard rice. We used a randomized, controlled, crossover study design with a washout period of 6 weeks between the two phases. Results : After the modified diet phase, body weight was significantly lower in both the non‐obese and obese subjects (non‐obese, 57.0 ± 2.9 vs. 56.1 ± 2.8 kg, p = 0.001; obese, 67.7 ± 2.1 vs. 65.7 ± 2.0 kg, p < 0.001 for before vs. after). The BMI was significantly lower in obese subjects (26.9 ± 0.5 vs. 26.0 ± 0.6 kg/m², p < 0.001). The modified diet was associated with lower serum triacylglycerol (p < 0.01), total cholesterol (p < 0.01), low‐density lipoprotein cholesterol (p < 0.05), and C‐peptide (p < 0.05) concentrations in the obese subjects. Discussion : These results indicate that fiber‐rich Goami No. 2 rice has beneficial effects and may be therapeutically useful for obese subjects.     

Loss‐of‐Function Mutations in MC4R Are Very Rare in the Greek Severely Obese Adult Population

Melanocortin‐4 receptor (MC4R) loss‐of‐function mutations are the commonest genetic cause of human monogenic obesity, so far. The contribution of MC4R coding mutations to severe obesity in the high‐obesity prone Greek population has not been investigated to date. We determined the MC4R coding sequence of 510 obese and 469 lean control subjects of Greek origin, and we estimated the prevalence and the penetrance on obesity of MC4R loss‐of‐function mutations. The functional impact of novel nonsynonymous variants detected was investigated in vitro. We found two novel synonymous mutations (L23L and I102I), four nonsynonymous mutations (T112M, S127L, N274S, and S295L), and two polymorphisms (V103I and I251L) previously described in literature. We also detected a novel mutation (L207V) in a severely obese 69‐year‐old female patient, although the mutation did not cosegregate with obesity in the corresponding pedigree and had no functional consequences on MC4R protein function. Loss‐of‐function mutations represented 75% of all nonsynonymous rare mutations identified among lean carriers and only 25% among obese subjects (P = 0.0001). The prevalence of loss‐of‐function mutations was lower in the obese group than in lean control subjects (0.20 vs. 0.64%) but this difference was not significant. Therefore, the estimated penetrance of deleterious MC4R mutations was very low (6.3%) in heterozygous Greek carriers of MC4R loss‐of‐function mutations. Our data suggest that MC4R loss‐of‐function mutations are rare in the Greek population. MC4R genetic deficiency is unlikely to explain the high propensity to develop severe obesity in this specific population.