Cellular program controlling the recovery of adipose tissue mass: An in vivo imaging approach

PPARγ activators such as rosiglitazone (RSG) stimulate adipocyte differentiation and increase subcutaneous adipose tissue mass. However, in addition to preadipocyte differentiation, adipose tissue expansion requires neovascularization to support increased adipocyte numbers. Paradoxically, endothelial cell growth and differentiation is potently inhibited by RSG in vitro, raising the question of how this drug can induce an increase in adipose tissue mass while inhibiting angiogenesis. We find that adipose tissue from mice treated with RSG have increased capillary density. To determine whether adipose tissue angiogenesis was stimulated by RSG, we developed a novel assay to study angiogenic sprout formation ex vivo. Angiogenic sprout formation from equally sized adipose tissue fragments, but not from aorta rings, was greatly increased by obesity and by TZD treatment in vivo. To define the mechanism involved in RSG-stimulated angiogenesis in adipose tissue, the expression of proangiogenic factors by adipocytes was examined. Expression of VEGFA and VEGFB, as well as of the angiopoietin-like factor-4 (ANGPTL4), was stimulated by in vivo treatment with RSG. To define the potential role of these factors, we analyzed their effects on endothelial cell growth and differentiation in vitro. We found that ANGPTL4 stimulates endothelial cell growth and tubule formation, albeit more weakly than VEGF. However, ANGPTL4 mitigates the growth inhibitory actions of RSG on endothelial cells in the presence or absence of VEGF. Thus, the interplay between VEGF and ANGPTL4 could lead to a net expansion of the adipose tissue capillary network, required for adipose tissue growth, in response to PPARγ activators.

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Limitation of adipose tissue by the number of embryonic progenitor cells

eLife ◽

10.7554/elife.53074 ◽

2020 ◽

Vol 9 ◽

Cited By ~ 1

Author(s):

Kristina Hedbacker ◽

Yi-Hsueh Lu ◽

Olof Dallner ◽

Zhiying Li ◽

Gulya Fayzikhodjaeva ◽

...

Keyword(s):

Adipose Tissue ◽

Es Cells ◽

Embryonic Stem ◽

Proliferative Potential ◽

Wild Type ◽

Tissue Mass ◽

Adipose Tissue Mass ◽

The Difference ◽

Turn Over

Adipogenesis in adulthood replaces fat cells that turn over and can contribute to the development of obesity. However, the proliferative potential of adipocyte progenitors in vivo is unknown (Faust et al., 1976; Faust et al., 1977; Hirsch and Han, 1969; Johnson and Hirsch, 1972). We addressed this by injecting labeled wild-type embryonic stem cells into blastocysts derived from lipodystrophic A-ZIP transgenic mice, which have a genetic block in adipogenesis. In the resulting chimeric animals, wild-type ES cells are the only source of mature adipocytes. We found that when chimeric animals were fed a high-fat-diet, animals with low levels of chimerism showed a significantly lower adipose tissue mass than animals with high levels of chimerism. The difference in adipose tissue mass was attributed to variability in the amount of subcutaneous adipose tissue as the amount of visceral fat was independent of the level of chimerism. Our findings thus suggest that proliferative potential of adipocyte precursors is limited and can restrain the development of obesity.

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Acylation-stimulating protein/C5L2-neutralizing antibodies alter triglyceride metabolism in vitro and in vivo

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00565.2006 ◽

2007 ◽

Vol 293 (6) ◽

pp. E1482-E1491 ◽

Cited By ~ 36

Author(s):

Wei Cui ◽

Sabina Paglialunga ◽

David Kalant ◽

HuiLing Lu ◽

Christian Roy ◽

...

Keyword(s):

Adipose Tissue ◽

Food Intake ◽

Glucose Transport ◽

Neutralizing Antibodies ◽

Tissue Mass ◽

Acylation Stimulating Protein ◽

Adipose Tissue Mass ◽

Ampk Activity

Acylation-stimulating protein (ASP), a lipogenic hormone, stimulates triglyceride (TG) synthesis and glucose transport upon activation of C5L2, a G protein-coupled receptor. ASP-deficient mice have reduced adipose tissue mass due to increased energy expenditure despite increased food intake. The objective of this study was to evaluate the blocking of ASP-C5L2 interaction via neutralizing antibodies (anti-ASP and anti-C5L2-L1 against C5L2 extracellular loop 1). In vitro, anti-ASP and anti-C5L2-L1 blocked ASP binding to C5L2 and efficiently inhibited ASP stimulation of TG synthesis and glucose transport. In vivo, neither anti-ASP nor anti-C5L2-L1 altered body weight, adipose tissue mass, food intake, or hormone levels (insulin, leptin, and adiponectin), but they did induce a significant delay in TG clearance [ P < 0.0001, 2-way repeated-measures (RM) ANOVA] and NEFA clearance ( P < 0.0001, 2-way RM ANOVA) after a fat load. After treatment with either anti-ASP or anti-C5L2-L1 antibody there was no change in adipose tissue AMPK activity, but neutralizing antibodies decreased perirenal TG mass (−38.4% anti-ASP, −18.8% anti-C5L2, P < 0.01–0.001) and perirenal LPL activity (−75.6% anti-ASP, −72.5% anti-C5L2, P < 0.05). In liver, anti-C5L2-L1 decreased TG mass (−42.8%, P < 0.05), whereas anti-ASP increased AMPK activity (+34.6%, P < 0.001). In the muscle, anti-C5L2-L1 significantly increased TG mass (+128.0%, P < 0.05), LPL activity (+226.1%, P < 0.001), and AMPK activity (+71.1%, P < 0.01). In addition, anti-ASP increased LPL activity (+164.4, P < 0.05) and AMPK activity (+53.9%, P < 0.05) in muscle. ASP/C5L2-neutralizing antibodies effectively block ASP-C5L2 interaction, altering lipid distribution and energy utilization.

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Measurement of brown adipose tissue mass using a novel dual-echo magnetic resonance imaging approach: A validation study

Metabolism ◽

10.1016/j.metabol.2013.03.002 ◽

2013 ◽

Vol 62 (8) ◽

pp. 1189-1198 ◽

Cited By ~ 27

Author(s):

Milja Holstila ◽

Kirsi A. Virtanen ◽

Tove J. Grönroos ◽

Jukka Laine ◽

Virva Lepomäki ◽

...

Keyword(s):

Magnetic Resonance Imaging ◽

Adipose Tissue ◽

Magnetic Resonance ◽

Validation Study ◽

Resonance Imaging ◽

Tissue Mass ◽

Brown Adipose ◽

Adipose Tissue Mass ◽

Imaging Approach ◽

Dual Echo

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MED19 Regulates Adipogenesis and Maintenance of White Adipose Tissue Mass by Mediating PPARγ-Dependent Gene Expression

Cell Reports ◽

10.1016/j.celrep.2020.108228 ◽

2020 ◽

Vol 33 (1) ◽

pp. 108228 ◽

Cited By ~ 1

Author(s):

John M. Dean ◽

Anyuan He ◽

Min Tan ◽

Jun Wang ◽

Dongliang Lu ◽

...

Keyword(s):

Gene Expression ◽

Adipose Tissue ◽

White Adipose Tissue ◽

Tissue Mass ◽

Adipose Tissue Mass

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Chemotactic cytokines, obesity and type 2 diabetes:in vivoandin vitroevidence for a possible causal correlation?

Proceedings of The Nutrition Society ◽

10.1017/s0029665109990218 ◽

2009 ◽

Vol 68 (4) ◽

pp. 378-384 ◽

Cited By ~ 41

Author(s):

Henrike Sell ◽

Jürgen Eckel

Keyword(s):

Insulin Resistance ◽

Adipose Tissue ◽

Low Grade ◽

Obese Patients ◽

Tissue Mass ◽

Tissue Biology ◽

Wide Range ◽

Adipose Tissue Mass

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.

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Triazole GHS-R1a antagonists JMV4208 and JMV3002 attenuate food intake, body weight, and adipose tissue mass in mice

Molecular and Cellular Endocrinology ◽

10.1016/j.mce.2014.06.003 ◽

2014 ◽

Vol 393 (1-2) ◽

pp. 120-128 ◽

Cited By ~ 6

Author(s):

M. Holubová ◽

V. Nagelová ◽

Z. Lacinová ◽

M. Haluzík ◽

D. Sýkora ◽

...

Keyword(s):

Body Weight ◽

Adipose Tissue ◽

Food Intake ◽

Tissue Mass ◽

Adipose Tissue Mass

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Relationships Between the Hypothalamus and Adipose Tissue Mass

Fuel Homeostasis and the Nervous System - Advances in Experimental Medicine and Biology ◽

10.1007/978-1-4684-5931-9_9 ◽

1991 ◽

pp. 99-105 ◽

Cited By ~ 1

Author(s):

Daniel A. K. Roncari

Keyword(s):

Adipose Tissue ◽

Tissue Mass ◽

Adipose Tissue Mass

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Fibroblast growth factor receptor 1 is a key regulator of early adipogenic events in human preadipocytes

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.90602.2008 ◽

2009 ◽

Vol 296 (1) ◽

pp. E121-E131 ◽

Cited By ~ 67

Author(s):

C. H. Widberg ◽

F. S. Newell ◽

A. W. Bachmann ◽

S. N. Ramnoruth ◽

M. C. Spelta ◽

...

Keyword(s):

Adipose Tissue ◽

Growth Factor ◽

Fibroblast Growth Factor ◽

Tissue Expansion ◽

Cell Number ◽

Fibroblast Growth ◽

Tissue Mass ◽

Proliferation And Differentiation ◽

Adipose Tissue Mass ◽

Human Preadipocytes

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.

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