scholarly journals Increased Gs Signaling in Osteoblasts Reduces Bone Marrow and Whole-Body Adiposity in Male Mice

Endocrinology ◽  
2016 ◽  
Vol 157 (4) ◽  
pp. 1481-1494 ◽  
Author(s):  
Corey J. Cain ◽  
Joel T. Valencia ◽  
Samantha Ho ◽  
Kate Jordan ◽  
Aaron Mattingly ◽  
...  

Abstract Bone is increasingly recognized as an endocrine organ that can regulate systemic hormones and metabolism through secreted factors. Although bone loss and increased adiposity appear to be linked clinically, whether conditions of increased bone formation can also change systemic metabolism remains unclear. In this study, we examined how increased osteogenesis affects metabolism by using an engineered G protein-coupled receptor, Rs1, to activate Gs signaling in osteoblastic cells in ColI(2.3)+/Rs1+ transgenic mice. We previously showed that these mice have dramatically increased bone formation resembling fibrous dysplasia of the bone. We found that total body fat was significantly reduced starting at 3 weeks of age. Furthermore, ColI(2.3)+/Rs1+ mice showed reduced O2 consumption and respiratory quotient measures without effects on food intake and energy expenditure. The mice had significantly decreased serum triacylglycerides, leptin, and adiponectin. Resting glucose and insulin levels were unchanged; however, glucose and insulin tolerance tests revealed increased sensitivity to insulin. The mice showed resistance to fat accumulation from a high-fat diet. Furthermore, ColI(2.3)+/Rs1+ mouse bones had dramatically reduced mature adipocyte differentiation, increased Wingless/Int-1 (Wnt) signaling, and higher osteoblastic glucose utilization than controls. These findings suggest that osteoblasts can influence both local and peripheral adiposity in conditions of increased bone formation and suggest a role for osteoblasts in the regulation of whole-body adiposity and metabolic homeostasis.

Author(s):  
Melina Gadagnotto Cezaroni ◽  
Leonardo Breda ◽  
Gabriel Keine Kuga ◽  
Rafael Calais Gaspar ◽  
Vitor Rosetto Muñoz ◽  
...  

Abstract Anthropometry is considered a widely applicable and effective method to track adiposity. Among the current methods of anthropometric analysis are the Body Mass Index (BMI) and the Waist Hip Index (ICQ) are utilized. However, both presents limitations because they fail to estimate the adiposity. In this sense, recently the Body Adiposity Index (IAC) emerged as an important tool in the adipose mass evaluation of large populations. Thus, the present study aimed to evaluate adults aged between 18 and 50 years through BMI, IAC and ICQ and to analyze the agreement degree between the methods. A total of 2602 individuals were analyzed, of which 1457 were women and 1145 men. After analyzing the data, it was verified that the majority of the population are within the standards of men was classified as not overweight only for ICQ and women for BMI and ICQ. In contrast the population of men is classified as healthy only for ICQ and women for BMI and ICQ. Concerning the agreement between the methods, only a positive and significant agreement between BMI and IAC was observed. Therefore, it can be concluded that IAC is an alternative for assessing body composition, showing a good method to estimate the percentage of total body fat of men and women, thus increasing the possibilities of diagnosis of obesity and overweight.


2012 ◽  
Vol 25 (1) ◽  
pp. 150-161 ◽  
Author(s):  
E. Louise Thomas ◽  
Gary Frost ◽  
Simon D. Taylor-Robinson ◽  
Jimmy D. Bell

Excess body adiposity, especially abdominal obesity and ectopic fat accumulation, are key risk factors in the development of a number of chronic diseases. The advent of in vivo imaging methodologies that allow direct assessment of total body fat and its distribution have been pivotal in this process. They have helped to identify a number of sub-phenotypes in the general population whose metabolic risk factors are not commensurate with their BMI. At least two such sub-phenotypes have been identified: subjects with normal BMI, but excess intra-abdominal (visceral) fat (with or without increased ectopic fat) and subjects with elevated BMI (> 25 kg/m2) but low visceral and ectopic fat. The former sub-phenotype is associated with adverse metabolic profiles, while the latter is associated with a metabolically normal phenotype, despite a high BMI. Here, examples of these phenotypes are presented and the value of carrying out enhanced phenotypical characterisation of subjects in interventional studies discussed.


2016 ◽  
pp. 1-5
Author(s):  
P. YOUNG ◽  
J. SHAH ◽  
C. ZHANG ◽  
D.C. FERRIS ◽  
I. COLON ◽  
...  

Studies suggest frailty occurs earlier in HIV-infected individuals, but data in postmenopausal HIV-infected women are lacking. We assessed the prevalence of frailty and association with anthropometric measures in HIV-infected and uninfected postmenopausal women. Fried’s frailty phenotype was measured in HIV-infected and uninfected Hispanic and African American postmenopausal women participating in a study of bone metabolism; fat and lean mass were measured by whole body dual energy x-ray absorptiometry (DXA). Multivariable logistic regression evaluated frailty risk factors. The study was conducted at Columbia University Medical Center between 2002 and 2007. The participants were 61 HIV-infected and 27 uninfected Hispanic and African American postmenopausal women. The study compared prevalence and predictors of frailty in HIV-infected and uninfected postmenopausal women. Prevalence of frailty tended to be higher among HIV-infected than uninfected controls (11.5% vs 0% p=0.07). Surprisingly, among HIV-infected women, total body fat, not lean mass, was associated with frailty in multivariate analysis. Higher prevalence of frailty in African American and Hispanic HIV-infected postmenopausal women (11.5%) was similar to the 11% prevalence reported in minority women who were 10 years older in the general population. Our data suggest that frailty occurs earlier in HIV-infected postmenopausal women, but larger longitudinal studies are necessary to confirm whether musculoskeletal aging is accelerated by HIV infection.


2006 ◽  
Vol 26 (2) ◽  
pp. 709-717 ◽  
Author(s):  
Helene Baribault ◽  
Jean Danao ◽  
Jamila Gupte ◽  
Li Yang ◽  
Banghua Sun ◽  
...  

ABSTRACT GPR103 is a G-protein-coupled receptor with reported expression in brain, heart, kidney, adrenal gland, retina, and testis. It encodes a 455-amino-acid protein homologous to neuropeptide FF2, neuropeptide Y2, and galanin GalR1 receptors. Its natural ligand was recently identified as 26RFa, a novel human RF-amide-related peptide with orexigenic activity. To identify the function of GPR103, we generated GPR103-deficient mice. Homozygous mutant mice were viable and fertile. Their body weight was undistinguishable from that of their wild-type littermates. Histological analysis revealed that GPR103−/− mice exhibited a thinned osteochondral growth plate, a thickening of trabecular branches, and a reduction in osteoclast number, suggestive of an early arrest of osteochondral bone formation. Microcomputed tomography confirmed the reduction in trabecular bone and connective tissue densities in GPR103 knockout animals. Whole-body radiography followed by morphometric analysis revealed a kyphosis in mutant animals. Reverse transcription-PCR analysis showed that GPR103 was expressed in human skull, mouse spine, and several osteoblast cell lines. Dexamethasone, a known inhibitor of osteoblast growth and inducer of osteoblast differentiation, inhibited GPR103 expression in human osteoblast primary cultures. Altogether, these results suggest that osteopenia in GPR103−/− mice may be mediated directly by the loss of GPR103 expression in bone.


2003 ◽  
Vol 88 (10) ◽  
pp. 4884-4890 ◽  
Author(s):  
Phillip E. Gates ◽  
Christopher L. Gentile ◽  
Douglas R. Seals ◽  
Demetra D. Christou

Abstract We sought to examine the influence of adiposity in age-associated changes in the left ventricle (LV) in a cohort of 113 healthy men, aged 20–79 yr, by measuring LV structure and diastolic function (echocardiography), whole body composition, and regional adiposity (dual energy x-ray absorptiometry). Aging was associated with increased levels of adiposity, greater wall thickness to chamber radius ratio, LV concentric remodeling, and reduced LV diastolic function (all P < 0.05). Bivariate correlation analysis showed that mean LV wall thickness, a concentric LV morphology, and diastolic function were related to adiposity (r = −0.63 to 0.51; all P < 0.05). The relation between age and both mean LV wall thickness and concentric remodeling was reduced after controlling for percentage total body fat (by 38% and 54%, respectively), percentage abdominal fat (by 42% and 62%), and the abdominal/thigh fat ratio (by 35% and 46%). The diastolic function-age relation was reduced after controlling for percentage total body fat (by 35%), percentage abdominal fat (by 39%), and the abdominal/thigh fat ratio (by 29%). There were no apparent differences in the contribution of percentage total body fat, percentage abdominal fat, or abdominal/thigh fat to the association between age and LV structure/diastolic function. We conclude that increasing adiposity contributes to the LV remodeling/reduced diastolic function that occurs with aging in healthy men.


1998 ◽  
Vol 85 (5) ◽  
pp. 1778-1785 ◽  
Author(s):  
E. Louise Thomas ◽  
Nadeem Saeed ◽  
Joseph V. Hajnal ◽  
Audrey Brynes ◽  
Anthony P. Goldstone ◽  
...  

In this study we assessed different magnetic resonance imaging (MRI) scanning regimes and examined some of the assumptions commonly made for measuring body fat content by MRI. Whole body MRI was used to quantify and study different body fat depots in 67 women. The whole body MRI results showed that there was a significant variation in the percentage of total internal, as well as visceral, adipose tissue across a range of adiposity, which could not be predicted from total body fat and/or subcutaneous fat. Furthermore, variation in the amount of total, subcutaneous, and visceral adipose tissue was not related to standard anthropometric measurements such as skinfold measurements, body mass index, and waist-to-hip ratio. Finally, we show for the first time subjects with a percent body fat close to the theoretical maximum (68%). This study demonstrates that the large variation in individual internal fat content cannot be predicted from either indirect methods or direct imaging techniques, such as MRI or computed tomography, on the basis of a single-slice sampling strategy.


Nutrients ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 4533
Author(s):  
Marc Villedon de Naide ◽  
Bruno Pereira ◽  
Daniel Courteix ◽  
Frederic Dutheil ◽  
Lucie Cassagnes ◽  
...  

Rheumatoid arthritis (RA) and spondyloarthritis (SpA) are associated with changes in body composition. Ectopic intramuscular fat (IMAT) may alter muscle function and contribute to cardiometabolic disorders. In a pilot study, we analyzed IMAT in the calf with peripheral quantitative computed tomography (pQCT) and examined correlations between IMAT quantity and body composition parameters. In 20 patients with active RA and 23 with active SpA, IMAT was correlated with visceral fat (VAT; r = 0.5143 and 0.6314, respectively; p < 0.05) and total lean mass (r = 0.5414 and 0.8132, respectively; p < 0.05), but not with whole body fat mass. Total lean mass mediated 16% and 33% of the effects of VAT on IMAT in RA and SpA, respectively. In both RA and SpA, calf muscle area was correlated with total lean mass (r = 0.5940 and r = 0.8597, respectively; p < 0.05) and fat area was correlated with total body fat (r = 0.6767 and 0.5089, respectively; p < 0.05) and subcutaneous fat (r = 0.6526 and 0.5524, respectively; p < 0.05). Fat area was inversely correlated with handgrip and walking tests, and it was associated with disease activity and disability. We showed that ectopic IMAT, measured with pQCT, was correlated with VAT, but not with total body fat, in RA and SpA. This result suggests that metabolically active fat was specifically associated with IMAT.


2015 ◽  
Vol 114 (11) ◽  
pp. 1852-1867 ◽  
Author(s):  
Yasmin Y. Al-Gindan ◽  
Catherine R. Hankey ◽  
Lindsay Govan ◽  
Dympna Gallagher ◽  
Steven B. Heymsfield ◽  
...  

AbstractThe reference organ-level body composition measurement method is MRI. Practical estimations of total adipose tissue mass (TATM), total adipose tissue fat mass (TATFM) and total body fat are valuable for epidemiology, but validated prediction equations based on MRI are not currently available. We aimed to derive and validate new anthropometric equations to estimate MRI-measured TATM/TATFM/total body fat and compare them with existing prediction equations using older methods. The derivation sample included 416 participants (222 women), aged between 18 and 88 years with BMI between 15·9 and 40·8 (kg/m2). The validation sample included 204 participants (110 women), aged between 18 and 86 years with BMI between 15·7 and 36·4 (kg/m2). Both samples included mixed ethnic/racial groups. All the participants underwent whole-body MRI to quantify TATM (dependent variable) and anthropometry (independent variables). Prediction equations developed using stepwise multiple regression were further investigated for agreement and bias before validation in separate data sets. Simplest equations with optimalR2and Bland–Altman plots demonstrated good agreement without bias in the validation analyses: men: TATM (kg)=0·198 weight (kg)+0·478 waist (cm)−0·147 height (cm)−12·8 (validation:R20·79, CV=20 %, standard error of the estimate (SEE)=3·8 kg) and women: TATM (kg)=0·789 weight (kg)+0·0786 age (years)−0·342 height (cm)+24·5 (validation:R20·84, CV=13 %, SEE=3·0 kg). Published anthropometric prediction equations, based on MRI and computed tomographic scans, correlated strongly with MRI-measured TATM: (R20·70−0·82). Estimated TATFM correlated well with published prediction equations for total body fat based on underwater weighing (R20·70–0·80), with mean bias of 2·5–4·9 kg, correctable with log-transformation in most equations. In conclusion, new equations, using simple anthropometric measurements, estimated MRI-measured TATM with correlations and agreements suitable for use in groups and populations across a wide range of fatness.


1987 ◽  
Vol 26 (06) ◽  
pp. 258-262
Author(s):  
J. Happi ◽  
R. P. Baum ◽  
J. Frohn ◽  
B. Weimer ◽  
A. Halbsguth ◽  
...  

The present study was done in order to examine if the use of111ln-DTPA- labeled MAb fragments in place of 131l-labeled MAb fragments increases the sensitivity of tomographic immunoscintigraphy to reach the level of that of planar imaging techniques. In 11 patients with various primary tumors, local recurrences or metastases [colorectal carcinoma (n = 7), ovarian carcinoma (n = 2), papillary thyroid carcinoma (n = 1), undifferentiated carcinoma of the lung (n = 1)], immunoscintigraphy (IS) was carried out using 111ln-DTPA- labeled F(ab’)2 fragments of various MAbs (anti-CEA, OC 125, anti-hTG) and planar and tomographic imaging were compared intraindividually. By conventional diagnostic procedures, the presence of a tumor mass was confirmed (transmission computer tomography, ultrasound) or verified (131l whole-body scintigraphy, histology) in all cases. Immunoscintigraphy was positive in 9 out of 11 cases by ECT and in 10 out of 11 cases by planar imaging. When using 111 In-labeled MAb fragments, intraindividual comparison of ECT and planar imaging resulted in a similar sensitivity. The increased sensitivity of ECT using this tracer in contrast to 131l-labeled MAb fragments may be attributed to the fact that the physical properties of111 In are much more suitable for the gamma cameras most commonly used (single detector, 3/8” crystal); using 111 In-labeled MAb fragments, count rates sufficient for ECT can be obtained within a reasonable acquisition time. This allows to combine IS with the advantages of ECT regarding tumour localization and prevention of artefacts due to superposition of background.


Diabetes ◽  
1992 ◽  
Vol 41 (9) ◽  
pp. 1151-1159 ◽  
Author(s):  
E. Bonora ◽  
S. Del Prato ◽  
R. C. Bonadonna ◽  
G. Gulli ◽  
A. Solini ◽  
...  

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