Involvement of serum vascular endothelial growth factor family members in the development of obesity in mice and humans☆

Gómez-Ambrosi, Javier; Catalán, Victoria; Rodríguez, Amaia; Ramírez, Beatriz; Silva, Camilo; Gil, Marı́a J.; Salvador, Javier; Frühbeck, Gema

doi:10.1016/j.jnutbio.2009.05.004

Cited by 67 publications

(67 citation statements)

References 46 publications

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“…Interestingly, transcript levels of Vegfa, a member of the VEGF family involved in angiogenesis in response to AT hypoxia, were markedly decreased in leptindeficient mice (Fig. 2d), which is in accordance with previous reports 38,43,44 . Moreover, iNOS deficiency further decreased Vegfa mRNA in EWAT of wild type and ob/ob mice (Fig.…”

Section: Resultssupporting

confidence: 93%

Targeted disruption of the iNOS gene improves adipose tissue inflammation and fibrosis in leptin-deficient ob/ob mice: role of tenascin C

et al. 2018

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Background/Objectives: Obesity is related to a dynamic extracellular matrix (ECM) remodeling, which involves the synthesis and degradation of different proteins, such as tenascin C (TNC) in the adipose tissue (AT). Given the functional relationship between leptin and inducible nitric oxide synthase (iNOS), our aim was to analyze the impact of the absence of the iNOS gene in AT inflammation and ECM remodeling in ob/ob mice. Subjects/Methods: The expression of genes involved in inflammation and ECM remodeling was evaluated in 10-week-old male double knockout (DBKO) mice simultaneously lacking the ob and iNOS genes as well as in ob/ob mice classified into three groups [control, leptin-treated (1 mg kg −1 day −1 ) and pair-fed]. Results: Leptin deficiency increased inflammation and fibrosis in AT. As expected, leptin treatment improved the obesity phenotype. iNOS deficiency in ob/ob mice improved insulin sensitivity, AT inflammation, and ECM remodeling, as evidenced by lower AT macrophage infiltration and collagen deposition, a downregulation of proinflammatory and profibrogenic genes Tnf, Emr1, Hif1a, Col6a1, Col6a3, and Tnc, as well as lower circulating TNC levels. Interestingly, leptin upregulated TNC expression and release in 3T3-L1 adipocytes, and iNOS knockdown in 3T3-L1 fat cells produced a significant decrease in basal and leptin-induced Tnc expression. Conclusions: Ablation of iNOS in leptin-deficient mice improved AT inflammation and ECM remodeling-related genes, attenuating fibrosis, and metabolic dysfunction. The activation of iNOS by leptin is necessary for the synthesis and secretion of TNC in adipocytes, suggesting an important role of this alarmin in the development of AT inflammation and fibrosis.

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Section: Resultssupporting

confidence: 93%

Targeted disruption of the iNOS gene improves adipose tissue inflammation and fibrosis in leptin-deficient ob/ob mice: role of tenascin C

et al. 2018

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“…25,26 Consistent with these studies and our finding of increased macrophage infiltration in obese mice, we noted a marked increase in VEGF-C expression in both serum (1.75-fold) and skin (2-fold) of HFD-fed obese C57BL/6J mice, as compared with their NCD-fed controls (Figures 3c and d). In addition, analysis of skin tissues from obese HFD-fed C57BL/6J mice also demonstrated increased expression of inflammatory cytokines including TNF-α (20-fold) and IL-1β (8.32-fold) as compared with their NCD controls (Figures 3e and f).…”

Section: Obesity Results In Perilymphatic Inflammationsupporting

confidence: 89%

“…50,51 Finally, T cell-derived cytokines including IFN-γ, IL-4 and IL-13 have been shown to directly inhibit lymphangiogenesis. 46,52 Consistent with previous studies in obese mice and patients, 26 we noted a marked increase in VEGF-C expression in tissues and serum harvested from obese HFD-fed C57BL/6J mice. This effect has a key role on glucose homeostasis in obesity by regulating macrophage infiltration and differentiation.…”

Section: Discussionsupporting

confidence: 91%

Obesity, But Not High Fat Diet, Impairs Lymphatic Function

Nores

Gardenier

Savetsky

et al. 2015

Journal of the American College of Surgeons

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“…35 In human obesity, although the VEGF protein has been found to be increased in circulation, 36,37 lower adipose tissue oxygen partial pressure in SAT of overweight/obese subjects did not induce an increase in hypoxia targets such as VEGF. 35 Angiogenesis is needed for efficient preadipocyte differentiation, but neovascularization is not triggered without adipocyte differentiation.…”

Section: Discussionmentioning

confidence: 96%

Relation between human LPIN1, hypoxia and endoplasmic reticulum stress genes in subcutaneous and visceral adipose tissue

et al. 2010

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Context: LPIN1 is the phosphatidic acid phosphatase that produces 1,2-diacylglycerol, and thus it is related to the synthesis of triglycerides in the adipocyte. LPIN1 has a role in lipid synthesis and nuclear receptor coactivation, both of which may be involved in lipid homeostasis and metabolism. Among others, hypoxia and endoplasmic reticulum (ER) stress are being shown to be related to the adipose dysfunction found in human obesity. Objective: The aim of this study was to analyze LPIN1 gene expression in human adipose tissue in parallel with several hypoxia, angiogenic, ER stress and peroxisome proliferator-activated receptor (PPAR)-related genes in human obesity. Design and Patients: Gene expression was quantified in abdominal (subcutaneous and visceral) adipose tissue from 62 subjects. Results: We have shown a marked association between LPIN1 and PPARa gene expression both in subcutaneous and visceral adipose tissues. Similarly, a strong interdependence with vascular endothelial growth factor (VEGF) gene expression was also described; in fact, LPIN1 and VEGF expression levels were significantly decreased with obesity to a similar extent. Conclusion: These associations might suggest a possible role of LPIN1 in stress conditions that occur in chronic obesity and underlie insulin resistance.

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Involvement of serum vascular endothelial growth factor family members in the development of obesity in mice and humans☆

Cited by 67 publications

References 46 publications

Targeted disruption of the iNOS gene improves adipose tissue inflammation and fibrosis in leptin-deficient ob/ob mice: role of tenascin C

Targeted disruption of the iNOS gene improves adipose tissue inflammation and fibrosis in leptin-deficient ob/ob mice: role of tenascin C

Obesity, But Not High Fat Diet, Impairs Lymphatic Function

Relation between human LPIN1, hypoxia and endoplasmic reticulum stress genes in subcutaneous and visceral adipose tissue

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