bluuebunny/crossref_metadata_2025 huggingface dataset:
Role of TRPM2 cation channels in dorsal root ganglion of rats after experimental spinal cord injury
Authors: Naziroğlu Mustafa , Uğuz Abdülhadi Cihangir , Ismailoğlu Özgür , Çiğ Bilal , Özgül Cemil , Borcak Muhammed
Published: March 2013

Introduction: We sought to determine the contribution of oxidative stress–dependent activation of TRPM2 and L‐type voltage‐gated Ca2+ channels (VGCC) in dorsal root ganglion (DRG) neurons of rats after spinal cord injury (SCI). Methods: The rats were divided into 4 groups: control; sham control; SCI; and SCI+nimodipine groups. The neurons of the SCI groups were also incubated with non‐specific TRPM2 channel blockers, 2‐aminoethoxydiphenylborate (2‐APB) and N‐(p‐amylcinnamoyl)anthranilic acid (ACA), before H2O2 stimulation. Results:The [Ca2+]i concentrations were higher in the SCI group than in the control groups, although their concentrations were decreased by nimodipine and 2‐APB. The H2O2‐induced TRPM2 current densities in patch‐clamp experiments were decreased by ACA and 2‐APB incubation. In the nimodipine group, the TRPM2 channels of neurons were not activated by H2O2 or cumene hydroperoxide. Conclusions: Increased Ca2+ influx and currents in DRG neurons after spinal injury indicated TRPM2 and voltage‐gated Ca2+ channel activation. Muscle Nerve 48: 945–950, 2013
Ultrasound diagnosis of bony nerve entrapment: Case series and literature review
Authors: Erra Carmen , Granata Giuseppe , Liotta Giovanna , Podnar Simon , Giannini Mauro , Kushlaf Hani , Hobson‐Webb Lisa D. , Leversedge Fraser J. , Martinoli Carlo , Padua Luca
Published: March 2013

Introduction: Nerve entrapment due to osseous callus formation is a rare complication after bone fracture. Electrodiagnostic studies and routine radiographic imaging often fail to demonstrate the pathology. The diagnosis is difficult and is often made incidentally upon surgical exploration. Nerve ultrasonography has not been used routinely to assess such lesions. Methods: We report 5 cases of nerve entrapment in osseous callus after fractures that occurred in 2011 and 2012. The diagnosis was made by ultrasound (US). We then performed a review of the relevant literature. Conclusions: US is becoming an invaluable tool for diagnosing peripheral nerve entrapments. The current cases suggest that nerve US should be strongly considered as an adjunctive diagnostic tool for nerve palsies developing after trauma. Muscle Nerve 48: 445–450, 2013
Creatine kinase response to high‐intensity aerobic exercise in adult‐onset muscular dystrophy
Authors: Andersen Søren P. , Sveen Marie‐Louise , Hansen Regitze S. , Madsen Karen L. , Hansen Jonas B. , Madsen Mads , Vissing John
Published: March 2013

Introduction

We investigated the effect of high‐intensity exercise on plasma creatine kinase (CK) in patients with muscular dystrophies.

Methods

Fourteen patients with Becker (BMD), facioscapulohumeral (FSHD), or limb‐girdle type 2 (LGMD2) muscular dystrophy, and 8 healthy subjects performed 5 cycling tests: an incremental max test, and tests at 65%, 75%, 85%, and 95% of maximal oxygen uptake (VO2max). Heart rate and oxygen consumption were measured during the tests, and plasma CK was measured before, immediately after, and 24 hours after exercise.

Results

All subjects were able to perform high‐intensity exercise at the different levels. In patients with LGMD2 and FSHD, CK normalized 24 hours after exercise compared with the pre‐exercise value, whereas those with BMD and healthy controls had elevated CK values 24 hours after exercise.

Conclusions

The findings suggest that high‐intensity exercise is generally well tolerated in patients with LGMD2 and FSHD, whereas those with BMD may be more prone to exercise‐induced damage. Muscle Nerve 48: 897–901, 2013
Phrenic nerve stimulation protects against mechanical ventilation‐induced diaphragm dysfunction in rats
Authors: Yang Meirong , Wang Haitao , Han Guangwei , Chen Lianhua , Huang Lina , Jiang Jihong , Li Shitong
Published: March 2013

Introduction: We investigated a novel application of phrenic nerve stimulation (PNS) in diaphragm dysfunction induced by mechanical ventilation (MV). Methods: Twenty‐one Sprague‐Dawley rats were assigned randomly to 3 groups: spontaneous breathing, 18‐h controlled MV, and 18‐h controlled MV with PNS. Upon completion of the experimental protocol, diaphragm contractility, gene expression of insulin‐like growth factor‐1 (IGF‐1) and ubiquitin ligases, and serum IGF‐1 levels were analyzed. Results: Compared with the spontaneously breathing rats, impaired diaphragm contractile function, including force‐related properties and force‐frequency responses, were pronounced with MV. Furthermore, MV suppressed IGF‐1 and induced muscle ring finger 1 mRNA expression in the diaphragm. In contrast, PNS counteracted MV‐induced gene expression changes in the diaphragm and restored diaphragm function. Conclusions: PNS exerted a protective effect against MV‐induced diaphragm dysfunction by counteracting altered expression of IGF‐1 and ubiquitin ligase in the diaphragm. Muscle Nerve 48: 958–962, 2013
IGF‐I attenuates FFA‐induced activation of JNK1 phosphorylation and TNFα expression in human subcutaneous preadipocytes
Authors: Neacsu Otilia , Cleveland Kelly , Xu Haiyan , Tchkonia Tamara T. , Kirkland James L. , Boney Charlotte M.
Published: March 2013

Objective

Free fatty acids (FFAs) are increased in visceral fat and contribute to insulin resistance through multiple mechanisms, including c‐Jun N‐terminal kinase (JNK) activation and expression of TNFα. Given that insulin‐like growth factor‐1 (IGF‐1)‐mediated proliferation is impaired in omental compared to subcutaneous (SC) preadipocytes, we investigated IGF‐I anti‐inflammatory action in preadipocytes from SC and omental adipose tissue.

Design and Methods

Preadipocytes isolated from abdominal SC and omental fat of obese subjects were studied in primary culture. Cells were exposed to FFAs with or without IGF‐I pretreatment followed by analysis of cytokine expression and JNK phosphorylation. Lentivirus infection was used to express a constitutively active AKT (myr‐AKT) in omental preadipocytes.

Results

FFAs increased the expression of tumor necrosis factor (TNF)α, interleukin (IL)‐6, and monocyte chemotactic protein (MCP)‐1 in SC and omental preadipocytes. IGF‐I pretreatment reduced FFA‐induced JNK1 phosphorylation and TNFα expression in SC but not omental preadipocytes. Treatment with the JNK1/2 inhibitor SP600125 reduced FFA‐induced expression of TNFα. FFAs and MALP‐2, a specific TLR2/6 ligand, but not specific ligands for TLR4 and TLR1/2, increased JNK1 phosphorylation. IGF‐I completely inhibited MALP‐2‐stimulated phosphorylation of JNK1. Expression of myr‐AKT in omental preadipocytes inhibited FFA‐stimulated JNK1 phosphorylation.

Conclusions

IGF‐I attenuated FFA‐induced JNK1 phosphorylation and TNFα expression through activation of AKT in human subcutaneous but not omental preadipocytes.
Ascending dose‐controlled trial of beloranib, a novel obesity treatment for safety, tolerability, and weight loss in obese women
Authors: Hughes T. E. , Kim D. D. , Marjason J. , Proietto J. , Whitehead J. P. , Vath J. E.
Published: March 2013

Objective: Evaluate the safety and tolerability of beloranib, a fumagillin‐class methionine aminopetidase‐2 (MetAP2) inhibitor, in obese women over 4 weeks.

Design and Methods: Thirty‐one obese (mean BMI 38 kg/m2) women were randomized to intravenous 0.1, 0.3, or 0.9 mg/m2 beloranib or placebo twice weekly for 4 weeks (N = 7, 6, 9, and 9).

Results: The most frequent AEs were headache, infusion site injury, nausea, and diarrhea. Nausea and infusion site injury occurred more with beloranib than placebo. The most common reason for discontinuation was loss of venous access. There were no clinically significant abnormal laboratory findings. In subjects completing 4 weeks, median weight loss with 0.9 mg/m2 beloranib was −3.8 kg (95% CI −5.1, −0.9; N = 8) versus −0.6 kg with placebo (−4.5, −0.1; N = 6). Weight change for 0.1 and 0.3 mg/m2 beloranib was similar to placebo. Beloranib (0.9 mg/m2) was associated with a significant 42 and 18% reduction in triglycerides and LDL‐cholesterol, as well as improvement in C‐reactive protein and reduced sense of hunger. Changes in β‐hydroxybutyrate, adiponectin, leptin, and fibroblast growth factor‐21 were consistent with the putative mechanism of MetAP2 inhibition. Glucose and blood pressure were unchanged.

Conclusions: Beloranib treatment was well tolerated and associated with rapid weight loss and improvements in lipids, C‐reactive protein, and adiponectin.
Increased β‐oxidation with improved glucose uptake capacity in adipose tissue from obese after weight loss and maintenance
Authors: Bouwman Freek G. , Wang Ping , van Baak Marleen , Saris Wim H.M. , Mariman Edwin C.M.
Published: March 2013

Objective

We investigated protein markers for pathways of the fatty acids (FAs) and glucose metabolism in human adipose tissue after a weight loss program by calorie restriction.

Methods

Overweight/obese subjects underwent an intervention of 5 weeks of a very low‐calorie diet followed by a 3‐week weight maintenance diet. Abdominal subcutaneous adipose tissue biopsies were sampled before and after the intervention. Seventeen target proteins as markers of metabolic pathways for the uptake and handling of FAs and glucose were quantified by Western blotting and 11 were retrieved from previous proteomics work. Correlation coefficients were calculated among changes of these proteins.

Results

Short‐chain 3‐hydroxyacyl‐CoA dehydrogenase, catalase, fatty acid translocase, fatty acid transporter protein 3, adipose triglyceride lipase, fatty acid‐binding protein 4, aldolase‐C, tubulin‐β‐5, and annexin A2 changed significantly, and lipoprotein lipase, perilipin 1, and hormone‐sensitive lipase tended to change. On an average, increased glucose transporter type 4 translocation was observed, supported by a consistent increase of tyr‐24 phosphorylated annexin A2.

Conclusions

Our findings suggest that after weight loss by calorie restriction and a short period of maintenance, adipose tissue has an increased capacity for glucose uptake, and lipid mobilization and oxidation. Such metabolic profile may relate to the health benefit of weight loss.
Effects of fructose and glucose overfeeding on hepatic insulin sensitivity and intrahepatic lipids in healthy humans
Authors: Lecoultre V. , Egli L. , Carrel G. , Theytaz F. , Kreis R. , Schneiter P. , Boss A. , Zwygart K. , Lê K‐A. , Bortolotti M. , Boesch C. , Tappy L.
Published: March 2013

Objective:

To assess how intrahepatic fat and insulin resistance relate to daily fructose and energy intake during short‐term overfeeding in healthy subjects.

Design and methods:

The analysis of the data collected in several studies in which fasting hepatic glucose production (HGP), hepatic insulin sensitivity index (HISI), and intrahepatocellular lipids (IHCL) had been measured after both 6‐7 days on a weight‐maintenance diet (control, C; n = 55) and 6‐7 days of overfeeding with 1.5 (F1.5, n = 7), 3 (F3, n = 17), or 4 g fructose/kg/day (F4, n = 10), with 3 g glucose/kg/day (G3, n = 11), or with 30% excess energy as saturated fat (fat30%, n = 10).

Results:

F3, F4, G3, and fat30% all significantly increased IHCL, respectively by 113 ± 86, 102 ± 115, 59 ± 92, and 90 ± 74% as compared to C (all P < 0.05). F4 and G3 increased HGP by 16 ± 10 and 8 ± 11% (both P < 0.05), and F3 and F4 significantly decreased HISI by 20 ± 22 and 19 ± 14% (both P < 0.01). In contrast, there was no significant effect of fat30% on HGP or HISI.

Conclusions:

Short‐term overfeeding with fructose or glucose decreases hepatic insulin sensitivity and increases hepatic fat content. This indicates short‐term regulation of hepatic glucose metabolism by simple carbohydrates.
Physicians build less rapport with obese patients
Authors: Gudzune Kimberly A. , Beach Mary Catherine , Roter Debra L. , Cooper Lisa A.
Published: March 2013

Objective

Physicians' negative attitudes toward patients with obesity are well documented. Whether or how these beliefs may affect patient–physician communication is unknown. To describe the relationship between patient body mass index (BMI) and physician communication behaviors (biomedical, psychosocial/lifestyle, and rapport building) during typical outpatient primary care visits was aimed.

Design and Methods

Using audio‐recorded outpatient encounters from 39 urban primary care physicians (PCPs) and 208 of their patients, the frequency of communication behaviors using the Roter Interaction Analysis System was examined. The independent variable was measured; patient BMI and dependent variables were communication behaviors by the PCP within the biomedical, psychosocial/lifestyle, and rapport building domains. A cross‐sectional analysis using multilevel Poisson regression models to evaluate the association between BMI and physician communication was performed.

Results

PCPs demonstrated less emotional rapport with overweight and obese patients (incidence rate ratio, IRR, 0.65, 95%CI 0.48‐0.88, P = 0.01; IRR 0.69, 95%CI 0.58‐0.82, P < 0.01, respectively) than for normal weight patients. No differences in PCPs' biomedical or psychosocial/lifestyle communication by patient BMI were found.

Conclusions

Our findings raise the concern that low levels of emotional rapport in primary care visits with overweight and obese patients may weaken the patient–physician relationship, diminish patients' adherence to recommendations, and decrease the effectiveness of behavior change counseling.
Obesity is associated with white matter atrophy: A combined diffusion tensor imaging and voxel‐based morphometric study
Authors: Karlsson Henry K. , Tuulari Jetro J. , Hirvonen Jussi , Lepomäki Virva , Parkkola Riitta , Hiltunen Jaana , Hannukainen Jarna C. , Soinio Minna , Pham Tam , Salminen Paulina , Nuutila Pirjo , Nummenmaa Lauri
Published: March 2013

Objective

Little is known about the mechanisms by which obesity influences brain structure. In this study, the obesity‐related changes in brain white and gray matter integrity were examined.

Design and Methods

23 morbidly obese subjects and 22 nonobese volunteers were studied using voxel‐based analysis of diffusion tensor imaging and of T1‐weighted MRI images. Full‐volume statistical parametric mapping analysis was used to compare fractional anisotropy (FA) and mean diffusivity (MD) values as well as gray (GM) and white matter (WM) density between these groups.

Results

Obese subjects had lower FA and MD values and lower focal and global GM and WM volumes than control subjects did. The focal structural changes were observed in brain regions governing reward seeking, inhibitory control, and appetite. Regression analysis showed that FA and MD values as well as GM and WM density were negatively associated with body fat percentage. Moreover, the volume of abdominal subcutaneous fat was negatively associated with GM density in most regions.

Conclusion

These findings imply that changes in GM and WM in obesity may be due to metabolic factors. Atrophy in regions involved in reward processing and appetite control may further promote abnormal reward seeking and eating behavior.
Association of lean body mass with cardiometabolic risk factors in healthy postmenopausal women
Authors: Peppa Melpomeni , Koliaki Chrysi , Boutati Eleni , Garoflos Efstathios , Papaefstathiou Athanasios , Siafakas Nikolaos , Katsilambros Nicholas , Raptis Sotirios A. , Hadjidakis Dimitrios I. , Dimitriadis George D.
Published: March 2013

Objective:

Aim of this study was to investigate the association of total and regional lean body mass (LBM) with cardiometabolic risk factors in healthy obese and nonobese postmenopausal women.

Methods:

A total of 150 postmenopausal women (age 54 ± 7 years, BMI 29.6 ± 5.8 kg/m2) underwent a comprehensive assessment of cardiometabolic risk, including metabolic syndrome (MS). Body composition analysis was performed with Dual‐energy X‐ray Absorptiometry, and multiple height‐adjusted indices of total and regional LBM were evaluated.

Results:

After controlling for age, diet, physical activity, and total fat mass, most indices of total, central, and peripheral LBM displayed significant positive correlations with cardiometabolic risk factors. Most associations were no longer significant after controlling for waist circumference, with the only exception of lean mass in the arms, which remained significantly associated with the presence and severity of MS (number of MS abnormalities), independently of central adiposity. A significant additive interaction was found between lean mass in the arms and waist circumference in increasing the prevalence of MS.

Conclusions:

LBM is unfavorably associated with cardiometabolic risk factors in healthy postmenopausal women. Whether LBM, especially in arms, is associated with cardiometabolic health independently of central fat distribution in postmenopausal women, merits further investigation.
NMR‐based metabolomics and breath studies show lipid and protein catabolism during low dose chronic T1AM treatment
Authors: Haviland J.A. , Reiland H. , Butz D.E. , Tonelli M. , Porter W.P. , Zucchi R. , Scanlan T.S. , Chiellini G. , Assadi‐Porter F.M.
Published: March 2013

Objective

3‐Iodothyronamine (T1AM), an analog of thyroid hormone, is a recently discovered fast‐acting endogenous metabolite. Single high‐dose treatments of T1AM have produced rapid short‐term effects, including a reduction of body temperature, bradycardia, and hyperglycemia in mice.

Design and Methods

The effect of daily low doses of T1AM (10 mg/kg) for 8 days on weight loss and metabolism in spontaneously overweight mice was monitored. The experiments were repeated twice (n = 4). Nuclear magnetic resonance (NMR) spectroscopy of plasma and real‐time analysis of exhaled 13CO2 in breath by cavity ring down spectroscopy (CRDS) were used to detect T1AM‐induced lipolysis.

Results

CRDS detected increased lipolysis in breath shortly after T1AM administration that was associated with a significant weight loss but independent of food consumption. NMR spectroscopy revealed alterations in key metabolites in serum: valine, glycine, and 3‐hydroxybutyrate, suggesting that the subchronic effects of T1AM include both lipolysis and protein breakdown. After discontinuation of T1AM treatment, mice regained only 1.8% of the lost weight in the following 2 weeks, indicating lasting effects of T1AM on weight maintenance.

Conclusions

CRDS in combination with NMR and 13C‐metabolic tracing constitute a powerful method of investigation in obesity studies for identifying in vivo biochemical pathway shifts and unanticipated debilitating side effects.
The efficacy of a daily self‐weighing weight loss intervention using smart scales and e‐mail
Authors: Steinberg Dori M. , Tate Deborah F. , Bennett Gary G. , Ennett Susan , Samuel‐Hodge Carmen , Ward Dianne S.
Published: March 2013

Objective

To examine the impact of a weight loss intervention that focused on daily self‐weighing for self‐monitoring as compared to a delayed control group among 91 overweight adults.

Design and Methods

The 6‐month intervention included a cellular‐connected “smart” scale for daily weighing, web‐based weight loss graph, and weekly e‐mails with tailored feedback and lessons. An objective measure of self‐weighing frequency was obtained. Weight was measured in clinic at 3 and 6 months. Caloric intake and expenditure, and perceptions of daily self‐weighing were also measured.

Results

Using intent‐to‐treat analyses, the intervention group lost significantly more weight compared to the control group [mean (95% CI); 3 months: −4.41% (−5.5, −3.3) vs. −0.37% (−1.5, 0.76); 6 months: −6.55% (−7.7, −5.4) vs. −0.35% (−1.5, 0.79); group × time interaction: P < 0.001] and a greater percentage achieved 5% (42.6% vs. 6.8%; P < 0.0001) and 10% (27.7% vs. 0%; P < 0.0001) weight loss. On average, the intervention group self‐weighed more days/week (6.1 ± 1.1 vs. 1.1 ± 1.5; P < 0.0001) and consumed fewer calories/day compared to the control group [mean (95% CI); 6 months: 1,509 (1,291, 1,728) vs. 1,856 (1,637, 2,074); group × time interaction: P = 0.006]. Among intervention participants, daily self‐weighing was perceived positively.

Conclusions

These results indicate that an intervention focusing on daily self‐weighing can produce clinically significant weight loss.
Body adiposity index and all‐cause and cardiovascular disease mortality in men
Authors: Moliner‐Urdiales Diego , Artero Enrique G. , Lee Duck‐chul , España‐Romero Vanesa , Sui Xuemei , Blair Steven N.
Published: March 2013

Objective

To evaluate the association of body adiposity index (BAI) with all‐cause and cardiovascular disease (CVD) mortality risk.

Design and Methods

The current analysis comprised 19,756 adult men who enrolled in the Aerobics Centre Longitudinal Study and completed a baseline examination during 1988‐2002. All‐cause and CVD mortality was registered till December 31, 2003.

Results

During an average follow‐up of 8.3 years (163,844 man‐years), 353 deaths occurred (101 CVD deaths). Age‐ and examination year‐adjusted hazard ratios (HRs) and 95% confidence intervals (95% CIs) for all‐cause mortality risk were higher for men with high values of BMI (HR = 1.63, 95% CI = 1.19‐2.23), waist circumference (1.55, 1.22‐1.96), and percentage of body fat (%BF) (1.36, 1.04‐1.31), but not for men with high values of BAI (1.28, 0.98‐1.66). The HRs for CVD mortality risks were higher for men with high values in all adiposity measures (HRs ranged from 1.73 to 2.06). Most of these associations, however, became nonsignificant after adjusting for multiple confounders including cardiorespiratory fitness.

Conclusion

BAI is not a better predictor of all‐cause and CVD mortality risk than BMI, waist circumference, or %BF.
Relationships between direct and indirect measures of central and total adiposity in children: What are we measuring?
Authors: Bigornia Sherman J. , LaValley Michael P. , Benfield Li L. , Ness Andy R. , Newby P.K.
Published: March 2013

Objective: The relationship between central and total fat measured by anthropometry, dual energy X‐ray absorptiometry, and magnetic resonance imaging (MRI) with each other and systolic blood pressure (SBP) was examined.

Design and Methods: Participants of the Avon Longitudinal Study of Parents and Children were examined at ages 9, 11, 13, and 15 years (n = 3,796‐6,567). MRI was available on a subset of children at 11 (n = 156) and 13 (n = 95).

Results: Body mass index (BMI) and waist circumference (WC) were highly correlated (r = 0.84‐0.91, across ages), and total body fat mass (TBFM) and trunk fat mass (TFM) were very strongly correlated (r ≥ 0.98). Among boys, BMI vs. WC explained a similar degree of variation in TBFM and TFM (41‐71% vs. 43‐76%, across age and overweight groups); in girls, BMI accounted for 62‐73% variance and WC 47‐69%. Adiposity measures were generally similarly correlated with SBP within age groups. Further, the relationship between intra‐abdominal adipose tissue (IAAT) volume and adiposity measures did not vary greatly at 11 (0.65‐0.67) and 13 (0.64‐0.67).

Conclusions: BMI and WC contain a large amount of overlapping information as evidenced by their high correlation and similarly sized associations with fat mass, SBP, and IAAT. This suggests that WC may be an inadequate marker of central adiposity during childhood.
Acute exercise induces a phenotypic switch in adipose tissue macrophage polarization in diet‐induced obese rats
Authors: Oliveira Alexandre G. , Araujo Tiago G. , Carvalho Bruno M. , Guadagnini Dioze , Rocha Guilherme Z. , Bagarolli Renata A. , Carvalheira Jose Barreto C. , Saad Mario J.A.
Published: March 2013

Objective

It has become clear that exercise may be a useful therapy in the insulin resistance treatment, as it has anti‐inflammatory effects and improves insulin sensitivity. However, it remains uncertain whether exercise affects the adipocytes or infiltrated macrophages. Thus, the aim was to investigate the effects of acute exercise on the inflammatory status and insulin signaling of the white adipose tissue (WAT) fractions (stromal‐vascular fraction [SVF] and adipocytes).

Design and Methods

The effect of acute swimming exercise was investigated on insulin sensitivity, insulin signaling, inflammatory pathways in the WAT fractions of high‐fat fed Wistar rats. Additionally, macrophage infiltration and polarization were analyzed in the WAT.

Results

Acute exercise can improve insulin signaling in WAT fractions, along with a phenotypic switch from M1‐ to M2‐macrophages in obese rats, as indicated by a marked increase in macrophage galactose‐type C‐type lectin 1‐positive cells in WAT was observed. Additionally, exercise promoted a reduction in circulating levels of lipopolysaccharide, and toll‐like receptor 4 activity along with TNF‐alpha, IL‐1‐beta and MCP‐1 mRNA levels in WAT fractions.

Conclusions

These data suggest that acute exercise improves insulin signaling in the WAT, at least in part by inducing macrophage polarization toward the M2‐state.
Molecular and morphologic characterization of superficial‐ and deep‐subcutaneous adipose tissue subdivisions in human obesity
Authors: Cancello Raffaella , Zulian Alessandra , Gentilini Davide , Maestrini Sabrina , Della Barba Alberto , Invitti Cecilia , Corà Davide , Caselle Michele , Liuzzi Antonio , Di Blasio Anna Maria
Published: March 2013

Objective

Human abdominal subcutaneous white adipose tissue (SAT) is composed of two different subcompartments: a “superficial” SAT (SSAT), located between the skin and a fibrous‐fascia plane; and a deeper SAT, located under this fibrous fascia plane, indicated as “deep” SAT (DSAT).

Design and Methods

In order to investigate whether SSAT and DSAT have different molecular and morphological features, paired SSAT/DSAT biopsies were collected from 10 female obese patients and used for microarray and morphologic analysis. The stroma‐vascular fraction cells were also isolated from both depots and cultured in vitro to assess the lipid accumulation rate.

Results

SSAT and DSAT displayed different patterns of gene expression, mainly for metabolic and inflammatory genes, respectively. Detailed gene expression analysis indicated that several metabolic genes, including adiponectin, are preferentially expressed in SSAT, whereas inflammatory genes are over‐expressed in DSAT. Despite a similar lipid accumulation rate in vitro, in vivo SSAT showed a significant adipocyte hypertrophy together with a significantly lower inflammatory infiltration and vascular vessel lumen mean size, when compared to DSAT.

Conclusions

These data show that, SSAT and DSAT are functionally and morphologically different and emphasize the importance of considering independent these two adipose depots when investigating SAT biology and obesity complications.
Effects of a specific MCHR1 antagonist (GW803430) on energy budget and glucose metabolism in diet‐induced obese mice
Authors: Zhang Li‐Na , Sinclair Rachel , Selman Colin , Mitchell Sharon , Morgan David , Clapham John C. , Speakman John R.
Published: March 2013

Objective

The melanin‐concentrating hormone (MCH) is a centrally acting peptide implicated in the regulation of energy homeostasis and body weight, although its role in glucose homeostasis is uncertain. Our objective was to determine effects of MCHR1 antagonism on energy budgets and glucose homeostasis in mice.

Methods

Effects of chronic oral administration of a specific MCHR1 antagonist (GW803430) on energy budgets and glucose homeostasis in diet‐induced obese (DIO) C57BL/6J mice were examined.

Results

Oral administration of GW803430 for 30 days reduced food intake, body weight, and body fat. Circulating leptin and triglycerides were reduced but insulin and nonesterified fatty acids were unaffected. Despite weight loss there was no improvement in glucose homeostasis (insulin levels and intraperitoneal glucose tolerance tests). On day 4‐6, mice receiving MCHR1 antagonist exhibited decreased metabolisable energy intake and increased daily energy expenditure. However these effects had disappeared by day 22‐24. Physical activity during the dark phase was increased by MCHR1 antagonist treatment throughout the 30‐day treatment.

Conclusions

GW803430 produced a persistent anti‐obesity effect due to both a decrease in energy intake and an increase in energy expenditure via physical activity but did not improve glucose homeostasis.
Assessment of Abdominal Fat Compartments Using DXA in Premenopausal Women From Anorexia Nervosa to Morbid Obesity
Authors: Bredella Miriam A. , Gill Corey M. , Keating Leigh K. , Torriani Martin , Anderson Ellen J. , Punyanitya Mark , Wilson Kevin E. , Kelly Thomas L. , Miller Karen K.
Published: March 2013

Objective: To test a newly developed dual energy X‐ray absorptiometry (DXA) method for abdominal fat depot quantification in subjects with anorexia nervosa (AN), normal weight, and obesity using CT as a gold standard.

Design and Methods: 135 premenopausal women (overweight/obese: n = 89, normal‐weight: n = 27, AN: n = 19); abdominal visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), and total adipose tissue (TAT) areas determined on CT and DXA.

Results: There were strong correlations between DXA and CT measurements of abdominal fat compartments in all groups with the strongest correlation coefficients in the normal‐weight and overweight/obese groups. Correlations of DXA and CT VAT measurements were strongest in the obese group and weakest in the AN group. DXA abdominal fat depots were higher in all groups compared to CT, with the largest % mean difference in the AN group and smallest in the obese group.

Conclusion: A new DXA technique is able to assess abdominal fat compartments including VAT in premenopausal women across a large weight spectrum. However, DXA measurements of abdominal fat were higher than CT, and this percent bias was most pronounced in the AN subjects and decreased with increasing weight, suggesting that this technique may be more useful in obese individuals.
Accuracy of SenseWear Pro2 Armband to Predict Resting Energy Expenditure in Childhood Obesity
Authors: Predieri Barbara , Bruzzi Patrizia , Lami Francesca , Vellani Giulia , Malavolti Marcella , Battistini Nino C , Iughetti Lorenzo
Published: March 2013

Objective: The accuracy of the SenseWear Pro2 Armband (SWA) in estimating resting energy expenditure (REE) in children and adolescents with obesity, using indirect calorimetry (IC) as a reference was evaluated.

Design and Methods: REE was assessed using both the SWA and IC in 40 obese subjects (26 M/14 F, age 11.5 ± 2.57 years, z‐score BMI 3.14 ± 0.53). The agreement between methods was assessed by the Bland‐Altman procedure. The relationship between REE assessments and patients' characteristics was also analyzed.

Results: SWA‐ and IC‐derived estimates of REE showed a significant correlation (r = 0.614; P < 0.001), but the SWA overestimated mean REE by 13% (P < 0.001). Age and kilogram of fat‐free mass (kg‐FFM) were significantly correlated with both REE estimation by SWA (r = 0.434 and r = 0.564, respectively) and IC (r = 0.401 and r = 0.518, respectively). Only kg‐FFM was demonstrated to be the main predictor factor of REE variability (r2 79% SWA; 75% IC).

Conclusions: The SWA overestimated mean REE in childhood obesity, suggesting that the SWA and IC are not yet interchangeable methods. This would require improving the SWA by developing better algorithms for predicting REE and, probably, bias in each individual REE could be reduced by an adjustment for subjects' kg‐FFM.
Probiotics L. plantarum and L. curvatus in Combination Alter Hepatic Lipid Metabolism and Suppress Diet‐Induced Obesity
Authors: Yoo Sae‐Rom , Kim Young‐Jae , Park Do‐Young , Jung Un‐Ju , Jeon Seon‐Min , Ahn Young‐Tae , Huh Chul‐Sung , McGregor Robin , Choi Myung Sook
Published: March 2013

Objective: To determine the effects of naturally derived probiotic strains individually or combination on a short‐term diet‐induced obesity model.

Design and Methods: C57BL/6J mice (n = 50) were randomly divided into five groups, then fed a high‐fat high‐cholesterol diet (HFCD), HFCD and Lactobacillus plantarum KY1032 (PL, 1010cfu/day), HFCD and Lactobacillus curvatus HY7601 (CU, 1010cfu/day), HFCD and in combination with PL+CU (1010cfu/day), or a normal diet (ND) for 9 weeks.

Results: PL and CU showed distinct and shared metabolic activity against a panel of 50 carbohydrates. Fat accumulation in adipose tissue and liver was significantly reduced by probiotic strains CU or PL+CU. Probiotic strains CU or PL+CU reduced cholesterol in plasma and liver, while PL+CL had a synergistic effect on hepatic triglycerides. Probiotic strains PL+CU combination was more effective for inhibiting gene expressions of various fatty acid synthesis enzymes in the liver, concomitant with decreases in fatty acid oxidation‐related enzyme activities and their gene expressions.

Conclusions: Multi‐strain probiotics may prove more beneficial than single‐strain probiotics to combat fat accumulation and metabolic alterations in diet‐induced obesity.
Effects of prescribing 1,000 versus 1,500 kilocalories per day in the behavioral treatment of obesity: A randomized trial
Authors: Nackers Lisa M. , Middleton Kathryn R. , Dubyak Pamela J. , Daniels Michael J. , Anton Stephen D. , Perri Michael G.
Published: March 2013

Objective

Controversy exists regarding the optimal energy prescription to promote successful long‐term behavioral management of obesity. Prescribing intake of 1,000 (vs. 1,500) kcal/day may produce larger initial weight reduction, but long‐term advantage remains unclear. The effects of prescribing 1,000 versus 1,500 kcal/day on 6‐ and 12‐month weight changes within behavioral treatment of obesity were examined.

Design and Methods

Participants were 125 obese women (mean ± SD; BMI = 37.84 ± 3.94 kg/m2) randomly assigned goals of 1,000 or 1,500 kcal/day.

Results

From months 0 to 6, participants prescribed 1,000 kcal/day lost more weight than those prescribed 1,500 kcal/day (mean ± SE = −10.03 ± 0.92g vs. −6.23 ± 0.94 kg, P = 0.045); however, from months 7 through 12, only the 1,000 kcal/day condition experienced a significant weight regain (1.51 ± 0.77 kg, P = 0.025). Baseline caloric consumption moderated the effect of treatment on regain; participants with baseline intakes ≧2,000 kcal/day who were assigned 1,000 kcal/day were significantly more susceptible to weight regain than those assigned 1,500 kcal/day (P = 0.049). At month 12, a significantly greater percentage of 1,000 kcal/day participants achieved weight reductions of 5% or more than those prescribed 1,500 kcal/day.

Conclusion

Encouraging obese individuals in behavioral treatment to adhere to a 1,000 kcal/day intake may increase their likelihood of achieving clinically meaningful weight losses.
Macrophage Gene Expression in Adipose Tissue is Associated with Insulin Sensitivity and Serum Lipid Levels Independent of Obesity
Authors: Ahlin S. , Sjöholm K. , Jacobson P. , Andersson‐Assarsson J.C. , Walley A. , Tordjman J. , Poitou C. , Prifti E. , Jansson P.‐A. , Borén J. , Sjöström L. , Froguel P. , Bergman R.N. , Carlsson L.M.S. , Olsson B. , Svensson P.‐A.
Published: March 2013

Objective: Obesity is linked to both increased metabolic disturbances and increased adipose tissue macrophage infiltration. However, whether macrophage infiltration directly influences human metabolism is unclear. The aim of this study was to investigate if there are obesity‐independent links between adipose tissue macrophages and metabolic disturbances.

Design and Methods: Expression of macrophage markers in adipose tissue was analyzed by DNA microarrays in the SOS Sib Pair study and in patients with type 2 diabetes and a BMI‐matched healthy control group.

Results: The expression of macrophage markers in adipose tissue was increased in obesity and associated with several metabolic and anthropometric measurements. After adjustment for BMI, the expression remained associated with insulin sensitivity, serum levels of insulin, C‐peptide, high density lipoprotein cholesterol (HDL‐cholesterol) and triglycerides. In addition, the expression of most macrophage markers was significantly increased in patients with type 2 diabetes compared to the control group.

Conclusion: Our study shows that infiltration of macrophages in human adipose tissue, estimated by the expression of macrophage markers, is increased in subjects with obesity and diabetes and associated with insulin sensitivity and serum lipid levels independent of BMI. This indicates that adipose tissue macrophages may contribute to the development of insulin resistance and dyslipidemia.
Association between obesity‐related gene FTO and ADHD
Authors: Choudhry Zia , Sengupta Sarojini M. , Grizenko Natalie , Thakur Geeta A. , Fortier Marie‐Eve , Schmitz Norbert , Joober Ridha
Published: March 2013

Objective

Attention‐deficit/hyperactivity disorder (ADHD) is an etiologically complex heterogeneous behavioral disorder. Several studies have reported that ADHD subjects are more likely to be overweight/obese and that this comorbidity may be due to shared genetic factors. The objective of this study is to explore the association between ADHD and FTO, a gene strongly associated with obesity in genome‐wide studies.

Design and Methods

One tag SNP (single‐nucleotide polymorphism, rs8050136, risk allele A) in the FTO gene was selected and its association with ADHD was tested. Family‐based association tests (FBATs) were conducted with the categorical diagnosis of ADHD as well as behavioral and cognitive phenotypes related to ADHD. Furthermore, stratified FBAT analyses based on maternal smoking during pregnancy (MSDP) status were conducted.

Results

Statistically significant associations were observed between rs8050136 and several of the traits tested in the total sample. These associations were stronger when the analysis was restricted to children who were not exposed to MSDP.

Conclusions

These exploratory results suggest the involvement of the FTO SNP rs8050136 in modulating the risk for ADHD, particularly in those children who were not exposed to MSDP. If confirmed, they may explain, at least in part, the complex links between obesity and ADHD.
Modeling metabolic syndrome through structural equations of metabolic traits, comorbid diseases, and GWAS variants
Authors: Karns Rebekah , Succop Paul , Zhang Ge , Sun Guangyun , Indugula Subba R. , Havas‐Augustin Dubravka , Novokmet Natalija , Durakovic Zijad , Milanovic Sanja Music , Missoni Sasa , Vuletic Silvije , Chakraborty Ranajit , Rudan Pavao , Deka Ranjan
Published: March 2013

Objective

To provide a quantitative map of relationships between metabolic traits, genome‐wide association studies (GWAS) variants, metabolic syndrome (MetS), and metabolic diseases through factor analysis and structural equation modeling (SEM).

Design and Methods

Cross‐sectional data were collected on 1,300 individuals from an eastern Adriatic Croatian island, including 14 anthropometric and biochemical traits, and diagnoses of type 2 diabetes, coronary heart disease, gout, kidney disease, and stroke. MetS was defined based on Adult Treatment Panel III criteria. Forty widely replicated GWAS variants were genotyped. Correlated quantitative traits were reduced through factor analysis; relationships between factors, genetic variants, MetS, and metabolic diseases were determined through SEM.

Results

MetS was associated with obesity (P< 0.0001), dyslipidemia (P< 0.0001), glycated hemoglobin (HbA1c;P= 0.0013), hypertension (P< 0.0001), and hyperuricemia (P< 0.0001). Of metabolic diseases, MetS was associated with gout (P= 0.024), coronary heart disease was associated with HbA1c (P< 0.0001), and type 2 diabetes was associated with HbA1c (P< 0.0001) and obesity (P= 0.008). Eleven GWAS variants predicted metabolic variables, MetS, and metabolic diseases. Notably, rs7100623 in HHEX/IDE was associated with HbA1c (β= 0.03;P< 0.0001) and type 2 diabetes (β= 0.326;P= 0.0002), underscoring substantial impact on glucose control.

Conclusions

Although MetS was associated with obesity, dyslipidemia, glucose control, hypertension, and hyperuricemia, limited ability of MetS to indicate metabolic disease risk is suggested.
Changes in fat and skeletal muscle with exercise training in obese adolescents: Comparison of whole‐body MRI and dual energy X‐ray absorptiometry
Authors: Lee SoJung , Kuk Jennifer L.
Published: March 2013

Objective

We examined skeletal muscle (SM) and fat distribution using whole‐body MRI in response to aerobic (AE) versus resistance exercise (RE) training in obese adolescents and whether DXA provides similar estimates of fat and SM change as MRI.

Design and Methods

Thirty‐nine obese boys (12‐18 years) were randomly assigned to one of three 3‐month interventions: AE (n = 14), RE (n = 14), or a control (n = 11).

Results

At baseline, MRI‐measured total fat was significantly greater than DXA‐measured total fat [△ = 3.1 kg (95% CI: −0.4 to 7.4 kg, P < 0.05)], wherein underestimation by dual energy X‐ray absorptiometry (DXA) was greatest in those with the highest total fat. Overall, the changes in total fat were not significantly different between MRI and DXA [△ = −0.4 kg (95% CI: −3.5 to 2.6 kg, P > 0.05)], but DXA tended to overestimate MRI fat losses in those with larger fat losses. MRI‐measured SM and DXA‐measured lean body mass were significantly correlated, but as expected the absolute values were different at baseline [△ = −28.4 kg (95% CI: −35.4 to −21.3 kg, P < 0.05)]. Further, DXA overestimated MRI gains in SM in those with larger SM gains.

Conclusions

Although DXA and MRI‐measured total and regional measures tended to be correlated at baseline and changes with exercise, there were substantial differences in the absolute values derived using DXA versus MRI. Further, there were systemic biases in the estimation between the methods wherein DXA tended to overestimate fat losses and SM gains compared to MRI. Thus, the changes in body composition observed are influenced by the method employed.
Changes in adipose glucocorticoid metabolism before and after bariatric surgery assessed by direct hormone measurements
Authors: Methlie Paal , Dankel Simon , Myhra Tone , Christensen Bjørn , Gjerde Jennifer , Fadnes Dag , Våge Villy , Løvås Kristian , Mellgren Gunnar
Published: March 2013

Objectives

Increased intra‐adipose cortisol is thought to promote obesity, but few human studies have investigated intra‐adipose glucocorticoid hormones and none have demonstrated prospective changes with fat loss.

Design and Methods

Subcutaneous adipose tissue (SAT) was obtained from obese subjects before and 1‐year after surgery‐induced fat loss, and from nonobese controls. In a second similar cohort of obese subjects, adipocytes and stromal‐vascular fraction were isolated. Intra‐adipose cortisol and cortisone levels were analyzed by liquid chromatography mass spectrometry and HSD11B1/HSD11B2 mRNA by qPCR.

Results

SAT cortisol/cortisone ratio before fat loss, median 4.8 (interquartile range, 4.1‐5.7), was higher than after fat loss, 1.9 (1.0‐2.7) (P = 0.001), and compared to nonobese controls, 3.2 (2.4‐3.9) (P = 0.005). Cortisone before fat loss, 2.3 (1.2‐2.9) nmol/kg, was lower than after fat loss, 5.8 (3.0‐10.2) nmol/kg (P = 0.042), and compared to controls, 5.1 (3.8‐6.7) nmol/kg (P = 0.013). HSD11B1 was predominantly expressed in mature adipocytes, whereas HSD11B2 was expressed at a higher level in stromal‐vascular fraction.

Conclusions

The intra‐adipose glucocorticoid metabolism was markedly altered in the extremely obese state with increased cortisol levels relative to cortisone, whereas fat loss restored this balance approximating nonobese subjects. Changes were more pronounced for cortisone than cortisol, suggesting an adaptive response to insufficient intra‐adipose cortisol levels in obesity.
Acylated ghrelin limits fat accumulation and improves redox state and inflammation markers in the liver of high‐fat‐fed rats
Authors: Barazzoni Rocco , Semolic Annamaria , Cattin Maria Rosa , Zanetti Michela , Guarnieri Gianfranco
Published: March 2013

Objective

Obesity commonly causes hepatic lipid accumulation that may favor oxidative stress and inflammation with negative clinical impact. Acylated ghrelin (A‐Ghr) modulates body lipid distribution and metabolism, and it may exert antioxidant effects in vitro as well as systemic anti‐inflammatory effects in vivo. The impact of A‐Ghr on liver triglyceride content, redox state and inflammation markers in diet‐induced obesity was investigated.

Design and Methods

A‐Ghr (200‐μg/injection: HFG) or saline (HF) were administered subcutaneously twice‐daily for 4 days to 12‐week‐old male rats fed a high‐fat diet for 1 month (n = 8–10/group).

Results

Compared to lean animals, liver triglyceride accumulation occurred in HF despite enhanced phosphorylation of the lipid oxidation regulator AMPK and preserved mitochondrial enzyme activities. High triglycerides were accompanied by pro‐oxidant changes in redox state and proinflammatory changes in NF‐kB and TNF‐alpha. A‐Ghr limited liver triglyceride excess (P < 0.05 HF > HFG > Control) with concomitant activation of glutathione peroxidase and normalized redox state and cytokines. A‐Ghr‐induced liver changes were associated with higher plasma adiponectin and lower circulating fatty acids (P < 0.05 HFG vs. HF).

Conclusions

A‐Ghr limits liver triglyceride accumulation and normalizes tissue redox state and inflammation markers in diet‐induced obese rats. These results suggest a favorable impact of A‐Ghr on hepatic complications of diet‐induced obesity.
Variation at the melanocortin 4 receptor gene and response to weight‐loss interventions in the diabetes prevention program
Authors: Pan Qing , Delahanty Linda M. , Jablonski Kathleen A. , Knowler William C. , Kahn Steven E. , Florez Jose C. , Franks Paul W. ,   Diabetes Prevention Program Research Group
Published: March 2013

Objective

To assess associations and genotype × treatment interactions for melanocortin 4 receptor (MC4R) locus variants and obesity‐related traits.

Design and Methods

Diabetes prevention program (DPP) participants (N = 3,819, of whom 3,356 were genotyped for baseline and 3,234 for longitudinal analyses) were randomized into intensive lifestyle modification (diet, exercise, weight loss), metformin or placebo control. Adiposity was assessed in a subgroup (n = 909) using computed tomography. All analyses were adjusted for age, sex, ethnicity and treatment.

Results

The rs1943218 minor allele was nominally associated with short‐term (6 month; P = 0.032) and long‐term (2 year; P = 0.038) weight change. Eight SNPs modified response to treatment on short‐term (rs17066856, rs9966412, rs17066859, rs8091237, rs17066866, rs7240064) or long‐term (rs12970134, rs17066866) reduction in body weight, or diabetes incidence (rs17066829) (all Pinteraction < 0.05).

Conclusion

This is the first study to comprehensively assess the role of MC4R variants and weight regulation in a weight loss intervention trial. One MC4R variant was directly associated with obesity‐related traits or diabetes; numerous other variants appear to influence body weight and diabetes risk by modifying the protective effects of the DPP interventions.