Context.-Hydroxycitric acid, the active ingredient in the herbal compound Garcinia cambogia, competitively inhibits the extramitochondrial enzyme adenosine triphosphate-citrate (pro-3S)-lyase. As a citrate cleavage enzyme that may play an essential role in de novo lipogenesis inhibition, G cambogia is claimed to lower body weight and reduce fat mass in humans. Objective.-To evaluate the efficacy of G cambogia for body weight and fat mass loss in overweight human subjects. Design.-Twelve-week randomized, double-blind, placebo-controlled trial. Setting.-Outpatient weight control research unit. Participants.-Overweight men and women subjects (mean body mass index [weight in kilograms divided by the square of height in meters], approximately 32 kg/m 2). Intervention.-Subjects were randomized to receive either active herbal compound (1500 mg of hydroxycitric acid per day) or placebo, and both groups were prescribed a high-fiber, low-energy diet. The treatment period was 12 weeks. Body weight was evaluated every other week and fat mass was measured at weeks 0 and 12. Main Outcome Measures.-Body weight change and fat mass change. Results.-A total of 135 subjects were randomized to either active hydroxycitric acid (n = 66) or placebo (n = 69); 42 (64%) in the active hydroxycitric acid group and 42 (61%) in the placebo group completed 12 weeks of treatment (P = .74). Patients in both groups lost a significant amount of weight during the 12-week treatment period (PϽ.001); however, between-group weight loss differences were not statistically significant (mean [SD], 3.2 [3.3] kg vs 4.1 [3.9] kg; P = .14). There were no significant differences in estimated percentage of body fat mass loss between treatment groups, and the fraction of subject weight loss as fat was not influenced by treatment group. Conclusions.-Garcinia cambogia failed to produce significant weight loss and fat mass loss beyond that observed with placebo.

Conventional single frequency bioimpedance analysis (BIA) systems require technician placement of arm and leg gel electrodes, a suitable location for recumbent measurements, and a separate measurement of body weight. The aim of this study was to evaluate a new single frequency 50 KHz leg-to-leg bioimpedance analysis (BIA) system combined with a digital scale that employs stainless steel pressure-contact foot pad electrodes for standing impedance and body weight measurements. Healthy adults were evaluated for 1) electrode validity and 2) potential for body component estimation. Pressure-contact foot-pad electrode measured impedance was highly correlated with (N = 9, r = 0.99, P < 0.001) impedance measured using conventional gel electrodes applied to the plantar surface of both lower extremities; mean (+/-SD) impedance was systematically higher by about 15 ohms for pressure contact electrodes (526 +/- 56 ohms vs 511 +/- 59 ohms; P < 0.001). Second, the relationship between stature-adjusted leg-to-leg impedance (H2/Z) measured by the new system and two body composition components (total body water by 3H2O dilution (N = 144); and fat-free body mass, by underwater weighing and dual x-ray absorptiometry (N = 231)) was modeled using multiple regression analysis. Correlation coefficients for H2/Z alone versus body composition components were lower for leg-to-leg BIA than for arm-to-leg BIA; correlation coefficients and SEEs became similar for the leg-to-leg and arm-to-leg BIA systems with addition of three covariates (age, gender, and waist/hip circumference ratio) to regression models. The leg-to-leg pressure contact electrode BIA system has overall performance characteristics for impedance measurement and body composition analysis similar to conventional arm-to-leg gel electrode BIA and offers the advantage of increased speed and ease of measurement.

Defective liver gluconeogenesis is the main mechanism leading to fasting hyperglycemia in type 2 diabetes, and, in concert with steatosis, it is the hallmark of hepatic insulin resistance. Experimental obesity results, at least in part, from hypothalamic inflammation, which leads to leptin resistance and defective regulation of energy homeostasis. Pharmacological or genetic disruption of hypothalamic inflammation restores leptin sensitivity and reduces adiposity. Here, we evaluate the effect of a hypothalamic anti-inflammatory approach to regulating hepatic responsiveness to insulin. Obese rodents were treated by intracerebroventricular injections, with immunoneutralizing antibodies against Toll-like receptor (TLR)4 or tumor necrosis factor (TNF)α, and insulin signal transduction, hepatic steatosis, and gluconeogenesis were evaluated. The inhibition of either TLR4 or TNFα reduced hypothalamic inflammation, which was accompanied by the reduction of hypothalamic resistance to leptin and improved insulin signal transduction in the liver. This was accompanied by reduced liver steatosis and reduced hepatic expression of markers of steatosis. Furthermore, the inhibition of hypothalamic inflammation restored defective liver glucose production. All these beneficial effects were abrogated by vagotomy. Thus, the inhibition of hypothalamic inflammation in obesity results in improved hepatic insulin signal transduction, leading to reduced steatosis and reduced gluconeogenesis. All these effects are mediated by parasympathetic signals delivered by the vagus nerve.

Objectives: Air displacement plethysmography (ADP) may provide a partial alternative to body density (B d ) and therefore body composition measurement compared to conventional hydrodensitometry (H d ) in children. As there are no evaluation studies of ADP in children, this study had a two-fold objective: to compare B d estimates by ADP and H d ; and to compare fat estimates by both ADP and H d to fat estimates by another reference method, dual energy X-ray absorptiometry (DXA). Setting: Obesity Research Center, St. Luke'saRoosevelt Hospital, New York, USA. Subjects: One hundred and twenty subjects (66 femalesa54 males) who ranged in age from 6 ± 86 y and in body mass index (BMI, kgam 2 ) from 14.1 ± 40.0 kgam 2 met study entry criteria. Study Design: Cross-sectional study of healthy children (age 19 y) and adult group for comparison to earlier studies. Each subject completed ADP, H d , and DXA studies on the same day. Only subjects with subjectivelyjudged successful H d studies were entered into the study cohort.Results: There was a high correlation between B d by ADP and H d (B d Hd 0.11 0.8966B d ADP; r 0.93, SEE 0.008 gacm 3 , P`0.0001), although the regression line slope and intercept differed signi®cantly from 1 and 0, respectively. Additional analyses localized a small-magnitude B d bias in the child (n 48) subgroup. Both ADP and H d %fat estimates were highly correlated (r b 0.9, P`0.0001) with %fat by DXA in child and adult subgroups. Bland ± Altman analyses revealed no signi®cant %fat bias by either ADP or H d vs DXA in either children or adults, although a bias trend (P 0.11) was detected in the child subgroup. Conclusion: With additional re®nements, the air displacement plethysmography system has the potential of providing an accurate and practical method of quantifying body fat in children as it now does in adults. Sponsorship: This study was in-part supported by NIH Grants RR00645, NIDDK 42618 and NIDDK 37352.

Obesity and caloric overfeeding are associated with the defective regulation of autophagy in the adipose tissue. The studies in obese-diabetic subjects undergoing improved metabolic control following calorie restriction suggest that autophagy and inflammation are regulated independently.

Objectives: Bioimpedance analysis (BIA) methods have potential to predict appendicular skeletal muscle mass (SM), although available 50 kHz prediction models include, in addition to impedance (Z), an independent age term. An age term in models is undesirable as it re¯ects incomplete understanding of underlying conduction physiology. This study tested the hypothesis, based on¯uid distribution models related to aging, that appendicular SM bioimpedance analysis (BIA) prediction models would no longer include an independent age term, after ®rst controlling for stature-adjusted appendicular impedance (height 2 aZ), at injected frequencies greater than 50 kHz. Design: Cross-sectional evaluation of adults who had segmental Z and phase angle (f) measured with multiple frequency BIA, and arm and leg SM with dual-energy X-ray absorptiometry (DXA). Skeletal muscle prediction models were developed with appendicular SM as dependent variable and height 2 aZ, gender, age and f as potential independent variables. Results: Examination of hypothesis in 49 subjects indicated: both arm and leg SM were highly correlated with height 2 asegmental Z at frequencies ranging from 1 ± 300 kHz; gender was signi®cant covariate in prediction models only at 1 kHz; age remained a signi®cant covariate after controlling for height 2 asegmental Z at all frequencies; f did not add signi®cantly to models; and SM prediction models gave maximum R 2 at 50 kHz for arm but R 2 continued to rise up to 300 kHz for leg. Conclusion: Although multifrequency BIA did not eliminate SM prediction model age term, our ®ndings suggest injected frequencies up to 300 kHz may have advantages for evaluating leg SM over conventional 50 kHz method.

There seems to be a substantial genetic contribution to fat mass distinct from BMI in a sample of children and adolescents. Studies testing putative genetic or environmental determinants of pediatric obesity might be strengthened further by including research-based body composition methods.

SummaryCrohn's disease (CD) is characterized by inflammation and an aetiology that is still unknown. Hypertrophy of mesenteric fat is a reflection of disease activity, as this fat covers the entire length of the affected area. Adipocytes synthesize leptin and adiponectin, adipocytokines responsible for pro-and anti-inflammatory effects. Therefore, we evaluated serum levels of adiponectin and leptin, as well as mesenteral expression of adiponectin in active CD and those in remission. Sixteen patients with ileocaecal CD followed at the Outpatient Clinic, Coloproctology Unit of University of Campinas Clinical Hospital, participated in the study. Analysis of serum adiponectin and leptin by enzyme-linked immunosorbent assay was performed in patients with active CD (ACD group), remission CD (RCD group) and in six healthy controls. Ten patients with active ileocaecal CD (FCD group) and eight patients with non-inflammatory disease selected for surgery were also studied. The specimens were snap-frozen and the expression of adiponectin was determined by immunoblot of protein extracts. Serum C-reactive protein levels were higher in the ACD group when compared to the others and no difference of body mass index was observed between the groups. Serum adiponectin was lower in the ACD group when compared to control, but no differences were seen when comparing the ACD and RCD groups. Mesenteric adiponectin expression was lower in the FCD group when compared to the FC group. Serum leptin was similar in all groups. The lower levels of serum and mesenteric adiponectin in active CD suggest a defective regulation of anti-inflammatory pathways in CD pathogenesis.