scholarly journals Loss of STAT5 in adipocytes increases subcutaneous fat mass via sex-dependent and depot-specific pathways

2021 ◽  
Author(s):  
Allison J. Richard ◽  
Hardy Hang ◽  
Timothy D. Allerton ◽  
Peng Zhao ◽  
Sujoy Ghosh ◽  
...  

SUMMARYThe STAT (Signal Transducers and Activators of Transcription) family of transcription factors contributes to adipocyte development and function. STAT5A and STAT5B are induced during adipocyte differentiation and are primarily activated by growth hormone (GH). Studies in mice lacking adipocyte GH receptor or STAT5 support their roles in lipolysis-mediated reduction of adipose tissue mass. We have generated a mouse model lacking both STAT5 genes specifically in adipocytes (STAT5AKO). Notably, both sexes of STAT5AKO mice have increased inguinal adipose tissue without any changes in gonadal fat mass. However, both depots exhibit substantial differences in fat cell size. Study of STAT5AKO mice also have revealed that GH’s ability to induce insulin resistance is dependent upon STAT5 in adipocytes, but its ability to reduce adipose tissue mass is STAT5 independent. Additional observations, which were not predicted, indicate that the causes and regulation of increased fat mass in STAT5AKO mice are sex- and depot-dependent.

2008 ◽  
Vol 93 (11) ◽  
pp. 4486-4493 ◽  
Author(s):  
Anders Rinnov Nielsen ◽  
Pernille Hojman ◽  
Christian Erikstrup ◽  
Christian Philip Fischer ◽  
Peter Plomgaard ◽  
...  

Objective: IL-15 decreases lipid deposition in preadipocytes and decreases the mass of white adipose tissue in rats, indicating that IL-15 may take part in regulating this tissue. IL-15 is expressed in human skeletal muscle and skeletal muscle may be a source of plasma IL-15 and in this way regulate adipose tissue mass. Design: The relation between skeletal muscle IL-15 mRNA expression, plasma IL-15, and adipose tissue mass was studied in 199 humans divided into four groups on the basis of obesity and type 2 diabetes. Furthermore, using a DNA electrotransfer model, we assessed the effect of IL-15 overexpression in skeletal muscle of mice. Results: In humans, multiple regression analysis showed a negative association between plasma IL-15 and total fat mass (P < 0.05), trunk fat mass (P < 0.01), and percent fat mass (P < 0.05), independent of type 2 diabetes. Negative associations were also found between muscle IL-15 mRNA and obesity parameters. IL-15 overexpression in skeletal muscle of mice reduced trunk fat mass but not sc fat mass. Conclusions: Our results indicate that IL-15 may be a regulator of trunk fat mass.


2020 ◽  
Vol 79 (OCE2) ◽  
Author(s):  
Ana Arpón ◽  
José-Ignacio Riezu-Boj ◽  
Fermín I. Milagro ◽  
José L. Santos ◽  
J. Alfredo Martínez

AbstractAdipose tissue is an endocrine organ involved in a variety of regulatory functions beyond simple fat storage. Excessive fat accumulation in the visceral tissue has been related to obesity associated comorbidities and manifestations such as hypertension, hyperglycaemia, hypercholesterolemia, and inflammatory processes. In the later stages of life, there is a shift of fat distribution from subcutaneous to visceral depots, which is associated to the development of several age-related diseases. Epigenetics has been described as a potential contributor in aging processes, being also associated with diseases and fat deposition that progress with age. The aim of this research was to investigate the relationships between aging, epigenetic processes and visceral adipose tissue.The study population included 269 adult subjects recruited in the University of Navarra, Spain. Methylation data was assessed by Infinium MethylationEPIC beadchip from Illumina. Epigenetic age acceleration was calculated using the method GrimAge (AgeAccGrim), available in the website DNA methylation Age Calculator (https://dnamage.genetics.ucla.edu/home). Anthropometric, biochemical and blood pressure measurements were assessed following standardized methods. Body composition measurements by DXA were also carried out.Statistically significant correlations were found between age acceleration and waist circumference, some DXA-measured variables (lean mass, trunk fat mass, android fat mass, visceral adipose tissue mass), glucose, HDL-cholesterol, triglycerides levels and C-reactive protein. Linear regression models showed that visceral adipose tissue mass and HDL-cholesterol were conjointly influencing the epigenetic age acceleration. In addition, a mediation by HDL-cholesterol in the relationship between AgeAccGrim and visceral adipose tissue mass was found.Collectively, these findings demonstrated that visceral adiposity and dyslipidaemia are associated with accelerated aging effects, contributing to understand the development of age-related diseases.


1997 ◽  
Vol 92 (1) ◽  
pp. 3-11 ◽  
Author(s):  
Johannes B. Prins ◽  
Stephen O'rahilly

1. Adipose tissue mass is dependent on both the average volume and the number of its constituent adipocytes. Significant alteration in body mass involves alteration in both adipocyte volume and number. 2. Increases in adipocyte number occur via replication and differentiation of preadipocytes, a process which occurs throughout life. Decreases in adipocyte number occur via preadipocyte and adipocyte apoptosis, and possibly adipocyte dedifferentiation. 3. Overall regulation of adipose mass involves endocrine, paracrine and possibly autocrine systems. Hypothalamic centres appear to control appetite, metabolic rate and activity levels in a co-ordinated manner. Within the hypothalamus, known weight regulatory molecules include glucagon-like peptide-1, neuropeptide Y and leptin. Leptin is a major afferent signal from adipose tissue to the hypothalamus, providing information on overall adipose tissue mass. However, the precise means by which the hypothalamus signals to adipose tissue is less well understood. 4. In adipose tissue, known molecular regulators of adipose cell number include insulin, ligands for the peroxisome proliferator activated receptor-γ, retinoids, corticosteroids and tumour necrosis factor-α. The net effect of these and other regulators is to effect a concerted alteration in adipocyte volume and number. This review largely focuses on the control of fat cell acquisition and loss and the influence of these processes on adipose tissue mass and regional distribution.


2013 ◽  
Vol 10 (2) ◽  
pp. 23-27
Author(s):  
T N Markova ◽  
V A Kichigin ◽  
V N Diomidova ◽  
D S Markov ◽  
O V Petrova

We performed an estimation of body fat using ultrasound, magnetic resonance imaging (MRI) and anthropometry in 60 patients with different types of body weight (BW). Correlation of waist circumference (WC), thickness of subcutaneous fat and visceral fat with components of the metabolic syndrome was studied comparatively between ultrasound and MRI measurements. We noted a preferential increase in the thickness of visceral fat compared with subcutaneous with increasing degree of BW. Significant increase in adipose tissue and the development of metabolic disorders occurs in overweight, making it the state close to obesity. During a routine ultrasound of the abdomen it is advisable to determine the thickness of subcutaneous and visceral fat separately.


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.


Cell Reports ◽  
2020 ◽  
Vol 33 (1) ◽  
pp. 108228 ◽  
Author(s):  
John M. Dean ◽  
Anyuan He ◽  
Min Tan ◽  
Jun Wang ◽  
Dongliang Lu ◽  
...  

2009 ◽  
Vol 68 (4) ◽  
pp. 378-384 ◽  
Author(s):  
Henrike Sell ◽  
Jürgen Eckel

A strong causal link between increased adipose tissue mass and insulin resistance in tissues such as liver and skeletal muscle exists in obesity-related disorders such as type 2 diabetes. Increased adipose tissue mass in obese patients and patients with diabetes is associated with altered secretion of adipokines, which also includes chemotactic proteins. Adipose tissue releases a wide range of chemotactic proteins including many chemokines and chemerin, which are interesting targets for adipose tissue biology and for biomedical research in obesity and obesity-related diseases. This class of adipokines may be directly linked to a chronic state of low-grade inflammation and macrophage infiltration in adipose tissue, a concept intensively studied in adipose tissue biology in recent years. The inflammatory state of adipose tissue in obese patients may be the most important factor linking increased adipose tissue mass to insulin resistance. Furthermore, chemoattractant adipokines may play an important role in this situation, as many of these proteins possess biological activity beyond the recruitment of immune cells including effects on adipogenesis and glucose homeostasis in insulin-sensitive tissues. The present review provides a summary of experimental evidence of the role of adipose tissue-derived chemotactic cytokines and their function in insulin resistancein vivoandin vitro.


2012 ◽  
Vol 166 (3) ◽  
pp. 469-476 ◽  
Author(s):  
L Frederiksen ◽  
K Højlund ◽  
D M Hougaard ◽  
T H Mosbech ◽  
R Larsen ◽  
...  

ObjectiveTestosterone therapy increases lean body mass and decreases total fat mass in aging men with low normal testosterone levels. The major challenge is, however, to determine whether the metabolic consequences of testosterone therapy are overall positive. We have previously reported that 6-month testosterone therapy did not improve insulin sensitivity. We investigated the effect of testosterone therapy on regional body fat distribution and on the levels of the insulin-sensitizing adipokine, adiponectin, in aging men with low normal bioavailable testosterone levels.DesignA randomized, double-blinded, placebo-controlled study on 6-month testosterone treatment (gel) in 38 men, aged 60–78 years, with bioavailable testosterone <7.3 nmol/l, and a waist circumference >94 cm.MethodsCentral fat mass (CFM) and lower extremity fat mass (LEFM) were measured by dual X-ray absorptiometry. Subcutaneous abdominal adipose tissue (SAT), visceral adipose tissue (VAT), and thigh subcutaneous fat area (TFA) were measured by magnetic resonance imaging. Adiponectin levels were measured using an in-house immunofluorometric assay. Coefficients (b) represent the placebo-controlled mean effect of intervention.ResultsLEFM was decreased (b=−0.47 kg, P=0.07) while CFM did not change significantly (b=−0.66 kg, P=0.10) during testosterone therapy. SAT (b=−3.0%, P=0.018) and TFA (b=−3.0%, P<0.001) decreased, while VAT (b=1.0%, P=0.54) remained unchanged. Adiponectin levels decreased during testosterone therapy (b=−1.3 mg/l, P=0.001).ConclusionTestosterone therapy decreased subcutaneous fat on the abdomen and lower extremities, but visceral fat was unchanged. Moreover, adiponectin levels were significantly decreased during testosterone therapy.


2014 ◽  
Vol 393 (1-2) ◽  
pp. 120-128 ◽  
Author(s):  
M. Holubová ◽  
V. Nagelová ◽  
Z. Lacinová ◽  
M. Haluzík ◽  
D. Sýkora ◽  
...  

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