scholarly journals Immune-Deficient Pfp/Rag2-/- Mice Featured Higher Adipose Tissue Mass and Liver Lipid Accumulation with Growing Age than Wildtype C57BL/6N Mice

Cells ◽  
2019 ◽  
Vol 8 (8) ◽  
pp. 775 ◽  
Author(s):  
Winkler ◽  
Hempel ◽  
Hsu ◽  
Gericke ◽  
Kühne ◽  
...  

Aging is a risk factor for adipose tissue dysfunction, which is associated with inflammatory innate immune mechanisms. Since the adipose tissue/liver axis contributes to hepatosteatosis, we sought to determine age-related adipose tissue dysfunction in the context of the activation of the innate immune system fostering fatty liver phenotypes. Using wildtype and immune-deficient mice, we compared visceral adipose tissue and liver mass as well as hepatic lipid storage in young (ca. 14 weeks) and adult (ca. 30 weeks) mice. Adipocyte size was determined as an indicator of adipocyte function and liver steatosis was quantified by hepatic lipid content. Further, lipid storage was investigated under normal and steatosis-inducing culture conditions in isolated hepatocytes. The physiological age-related increase in body weight was associated with a disproportionate increase in adipose tissue mass in immune-deficient mice, which coincided with higher triglyceride storage in the liver. Lipid storage was similar in isolated hepatocytes from wildtype and immune-deficient mice under normal culture conditions but was significantly higher in immune-deficient than in wildtype hepatocytes under steatosis-inducing culture conditions. Immune-deficient mice also displayed increased inflammatory, adipogenic, and lipogenic markers in serum and adipose tissue. Thus, the age-related increase in body weight coincided with an increase in adipose tissue mass and hepatic steatosis. In association with a (pro-)inflammatory milieu, aging thus promotes hepatosteatosis, especially in immune-deficient mice.

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.


FEBS Letters ◽  
2004 ◽  
Vol 577 (3) ◽  
pp. 351-356 ◽  
Author(s):  
Javier Gómez-Ambrosi ◽  
Sara Becerril ◽  
Paula Oroz ◽  
Santiago Zabalza ◽  
Amaia Rodrı́guez ◽  
...  

Obesity ◽  
2014 ◽  
Vol 23 (2) ◽  
pp. 335-344 ◽  
Author(s):  
Jialin Xu ◽  
Ajay C. Donepudi ◽  
Vijay R. More ◽  
Supriya R. Kulkarni ◽  
Liya Li ◽  
...  

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.


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

2009 ◽  
Vol 296 (1) ◽  
pp. E121-E131 ◽  
Author(s):  
C. H. Widberg ◽  
F. S. Newell ◽  
A. W. Bachmann ◽  
S. N. Ramnoruth ◽  
M. C. Spelta ◽  
...  

Cell number is an important determinant of adipose tissue mass, and the coordinated proliferation and differentiation of preadipocytes into mature lipid-laden adipocytes underpins the increased adipose tissue mass associated with obesity. Despite this, the molecular cues governing such adipose tissue expansion are poorly understood. We previously reported that fibroblast growth factor-1 (FGF-1) promotes both proliferation and differentiation of human preadipocytes and that the major adipogenic effect of FGF-1 occurs during proliferation, priming the cells for adipose conversion. In the current study, we examined whether this effect was linked to the mitogenic action of FGF-1 by investigating the mitogenic and adipogenic potential of other growth factors, platelet-derived growth factor (PDGF; AA and BB) and vascular endothelial growth factor. Although PDGF-AA and PDGF-BB showed comparable mitogenic potential to FGF-1, only FGF-1 treatment resulted in priming and subsequent differentiation. Pharmacological inhibition of FGF receptor (FGFR) tyrosine kinase activity, using the FGFR-specific inhibitors PD-173074 and SU-5402, revealed an obligate requirement for FGFR activity in these processes. A combination of biochemical and genetic approaches revealed an important role for FGFR1. Knock down of FGFR1 expression by small-interfering RNA reduced FGF-1-stimulated signaling events, proliferation, and priming. Together these data highlight the unique nature of the role of FGF-1 during the earliest stages of adipogenesis and establish a role for FGFR1 in human adipogenesis, identifying FGFR1 as a potential therapeutic target to reduce obesity.


2018 ◽  
Vol 49 (1) ◽  
pp. 9-15 ◽  
Author(s):  
Takashi Abe ◽  
Jeremy P. Loenneke ◽  
Robert S. Thiebaud

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