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

2007 ◽  
Vol 293 (6) ◽  
pp. E1482-E1491 ◽  
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.

scholarly journals Enhanced angiogenesis in obesity and in response to PPARγ activators through adipocyte VEGF and ANGPTL4 production

2008 ◽  
Vol 295 (5) ◽  
pp. E1056-E1064 ◽  
Author(s):  
Olga Gealekman ◽  
Alison Burkart ◽  
My Chouinard ◽  
Sarah M. Nicoloro ◽  
Juerg Straubhaar ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Endothelial Cell ◽  
Cell Growth ◽  
Tissue Mass ◽  
Adipose Tissue Mass ◽  
Cell Growth And Differentiation ◽  
Endothelial Cell Growth ◽  
Sprout Formation

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.

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

2009 ◽  
Vol 68 (4) ◽  
pp. 378-384 ◽  
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.

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

2014 ◽  
Vol 393 (1-2) ◽  
pp. 120-128 ◽  
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

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

2008 ◽  
Vol 105 (35) ◽  
pp. 12985-12990 ◽  
Author(s):  
K. Birsoy ◽  
A. Soukas ◽  
J. Torrens ◽  
G. Ceccarini ◽  
J. Montez ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
In Vivo Imaging ◽  
Tissue Mass ◽  
Adipose Tissue Mass ◽  
Imaging Approach

Enhanced triglyceride clearance with intraperitoneal human acylation stimulating protein in C57BL/6 mice

1999 ◽  
Vol 277 (3) ◽  
pp. E474-E480 ◽  
Author(s):  
Ian Murray ◽  
Allan D. Sniderman ◽  
Katherine Cianflone
Keyword(s):  
Adipose Tissue ◽  
Area Under The Curve ◽  
Human Adipose Tissue ◽  
Plasma Triglyceride ◽  
Complement C3 ◽  
Postprandial Period ◽  
Postprandial Triglyceride ◽  
Acylation Stimulating Protein

Acylation stimulating protein (ASP), a novel adipocyte-derived autocrine protein, stimulates triglyceride synthesis and glucose transport in vitro in human and murine adipocytes. In vitro, chylomicrons increase ASP and precursor complement C3 production in adipocytes. Furthermore, in vivo, ASP production from human adipose tissue correlates positively with triglyceride clearance postprandially. The aim of the present study was to determine if intraperitoneally injected ASP accelerated triglyceride clearance in vivo after a fat load in C57Bl/6 mice. ASP increased the triglyceride clearance with a reduction of the triglyceride area under the curve over 6 h (AUC0–6) from 102.6 ± 30.0 to 61.0 ± 14.5 mg ⋅ dl−1 ⋅ h−1( P < 0.05), especially in the latter postprandial period (AUC3–6; 56.2 ± 18.0 vs. 24.9 ± 8.9 mg ⋅ dl−1 ⋅ h−1, P < 0.025). ASP also reduced plasma glucose both in the mice with accelerated plasma triglyceride clearance and in those with relatively delayed triglyceride clearance ( P < 0.025). Therefore, ASP alters postprandial triglyceride and glucose metabolism.

scholarly journals JAZF1 heterozygous knockout mice show altered adipose development and metabolism

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Jain Jeong ◽  
Soyoung Jang ◽  
Song Park ◽  
Wookbong Kwon ◽  
Si-Yong Kim ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Knockout Mice ◽  
Metabolic Disorders ◽  
Adipocyte Differentiation ◽  
Zinc Finger Protein ◽  
Tissue Mass ◽  
In Vivo Models ◽  
Brown Adipose

Abstract Background Juxtaposed with another zinc finger protein 1 (JAZF1) is associated with metabolic disorders, including type 2 diabetes mellitus (T2DM). Several studies showed that JAZF1 and body fat mass are closely related. We attempted to elucidate the JAZF1 functions on adipose development and related metabolism using in vitro and in vivo models. Results The JAZF1 expression was precisely regulated during adipocyte differentiation of 3T3-L1 preadipocyte and mouse embryonic fibroblasts (MEFs). Homozygous JAZF1 deletion (JAZF1-KO) resulted in impaired adipocyte differentiation in MEF. The JAZF1 role in adipocyte differentiation was demonstrated by the regulation of PPARγ—a key regulator of adipocyte differentiation. Heterozygous JAZF1 deletion (JAZF1-Het) mice fed a normal diet (ND) or a high-fat diet (HFD) had less adipose tissue mass and impaired glucose homeostasis than the control (JAZF1-Cont) mice. However, other metabolic organs, such as brown adipose tissue and liver, were negligible effect on JAZF1 deficiency. Conclusion Our findings emphasized the JAZF1 role in adipocyte differentiation and related metabolism through the heterozygous knockout mice. This study provides new insights into the JAZF1 function in adipose development and metabolism, informing strategies for treating obesity and related metabolic disorders.

Glucose-Dependent Uptake of Chromium in Human and Rat Insulin-Sensitive Tissues

1993 ◽  
Vol 84 (4) ◽  
pp. 477-482 ◽  
Author(s):  
Brian W. Morris ◽  
Trevor A. Gray ◽  
Sheila MacNeil
Keyword(s):  
Adipose Tissue ◽  
Human Plasma ◽  
Glucose Transport ◽  
Blood Cells ◽  
Human Adipose Tissue ◽  
Trivalent Chromium ◽  
Blood Compartment

1. This study was designed to investigate the influence of insulin and glucose on the distribution of trivalent chromium in human plasma and blood cells and in human and rat insulin-sensitive and -insensitive tissues. 2. Evidence is provided that, in the rat in vitro, a clear difference exists in chromium binding between insulin-sensitive and -insensitive tissues in that chromium binding is significantly enhanced by glucose in insulin-sensitive tissues. 3. Glucose-dependent association of chromium with human adipose tissue was blocked by inhibitors of glucose transport. 4. Addition of insulin slightly increased the response to glucose in muscle and reduced the response to glucose in adipose tissue; such effects were less marked than those seen in response to glucose alone. 5. The results of this study in vitro support the hypothesis that, in vivo, chromium translocates from the blood compartment to insulin-sensitive tissues.

Insulin binding and action in adipocytes in vitro in relation to insulin action in vivo in young and middle-aged subjects

1986 ◽  
Vol 113 (1) ◽  
pp. 88-92 ◽  
Author(s):  
Hannele Yki-Jarvinen ◽  
Tuula Kiviluoto ◽  
Esko A. Nikkila
Keyword(s):  
Adipose Tissue ◽  
Glucose Metabolism ◽  
Glucose Uptake ◽  
Glucose Transport ◽  
Young Group ◽  
Middle Aged ◽  
Young Subjects ◽  
Aged Subjects

Abstract. The effect of age on glucose metabolism in vivo was compared to that found in adipocytes in vitro in young (n = 8, age 23 to 31 years) and middle-aged (n = 7, age 37 to 55 years) non-diabetic subjects. During the OGTT, the incremental glucose or insulin areas did not differ significantly between the groups. Fasting and 2 h plasma glucose (P < 0.01) and the 2 h plasma insulin (P < 0.05) levels were, however, slightly higher in the middle-aged than in the young group. During iv induced hyperinsulinaemia (~ 85 mU/l), rates of glucose uptake were comparable between the middle-aged (6.32 ± 0.94 mg/kg/min) and the young subjects (7.56 ± 0.78 mg/kg/min, P > 0.5). In fat cells, both basal and insulin stimulated rates of glucose transport were 35% lower (P < 0.05) in the middle-aged than in the young subjects. Basal and insulin stimulated rates of glucose oxidation and lipogenesis were both markedly lower (P <0.01) in the middle-aged than in the young group. The rates of glucose transport, oxidation and lipogenesis were inversely related to age, whereas none of these parameters was related to fat cell size. In conclusion, adipocyte glucose metabolism in middle-aged healthy subjects was markedly impaired. In contrast, rates of glucose uptake during iv hyperinsulinaemia and glucose responses during hyperinsulinaemia in the OGTT were comparable in young and middle-aged subjects. These results indicate first, that changes in adipose tissue glucose metabolism by aging do not parallel changes in whole body glucose metabolism and thus are specific for adipose tissue. Secondly, insulin-mediated glucose uptake is not reduced in middle-aged subjects. Thus, the small elevation in fasting and 2-h glucose levels may reflect a reduction in glucose uptake by non-insulin dependent pathways by aging.

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