Macrophage infiltration and cytokine release in adipose tissue: angiogenesis or inflammation?
ABSTRACT The observation that obese adipose tissue was infiltrated by macrophages triggered the concept that type 2 diabetes is a low-grade
inflammatory disease. In this review, we re-evaluate the role of macrophage infiltration, TNFα secretion and IKKβ/JNK signalling
in insulin resistance, and put forward the hypothesis that these intermediates are important mediators of adipose tissue angiogenesis.
Expansion of adipose tissue vasculature is essential to support adipose tissue growth during development and adipose tissue
expansion in adulthood. We propose that a major role of so-called pro-inflammatory adipokines is to stimulate adipose tissue
angiogenesis to support the nutrient requirements of expanding fat depots. Inhibition of angiogenesis overrides insulin resistance
and obesity not by blocking the peripheral effects of the inflammatory pathway on insulin resistance, but rather by central
effects on food intake. This unveils a possible feedback loop involving adipose angiogenesis and central regulation of food
intake that is independent of a classical immune response.
KeywordsAngiogenesis-Macrophages-Inflammation-Adipose tissue-Insulin resistance-Adipokines
- SourceAvailable from: Marco Presta[show abstract] [hide abstract]
ABSTRACT: The long pentraxin PTX3 is a soluble pattern recognition receptor produced by monocytes and endothelial cells that plays a nonredundant role in inflammation. Several pathologic conditions are characterized by local production of both PTX3 and the angiogenic fibroblast growth factor-2 (FGF2). Here, solid-phase binding assays demonstrated that PTX3 binds with high affinity to FGF2 but not to a panel of cytokines and growth factors, including FGF1, FGF4, and FGF8. Accordingly, PTX3 prevented (125)I-FGF2 binding to endothelial cell receptors, leading to specific inhibition of FGF2-induced proliferation. PTX3 hampered also the motogenic activity exerted by endogenous FGF2 on a wounded endothelial cell monolayer. Moreover, PTX3 cDNA transduction in FGF2-transformed endothelial cells inhibited their autocrine FGF2-dependent proliferation and morphogenesis in vitro and their capacity to generate vascular lesions when injected in nude mice. Finally, PTX3 suppressed neovascularization triggered by FGF2 in the chick embryo chorioallantoic membrane with no effect on physiologic angiogenesis. In contrast, the short pentraxin C-reactive protein was a poor FGF2 ligand/antagonist. These results establish the selective binding of a member of the pentraxin superfamily to a growth factor. PTX3/FGF2 interaction may modulate angiogenesis in various physiopathologic conditions driven by inflammation, innate immunity, and/or neoplastic transformation.Blood 08/2004; 104(1):92-9. · 9.06 Impact Factor
- [show abstract] [hide abstract]
ABSTRACT: Angiotensinogen shares with other members of the serine protease inhibitor (serpin) family antiangiogenic properties. Angiotensinogen inhibits in vitro endothelial cell proliferation, and is antiangiogenic in ovo in the chick chorioallantoic membrane assay. The cellular mode of action of angiotensinogen has been studied by applying purified human angiotensinogen or Chinese hamster ovary cells producing recombinant angiotensinogen onto the developing chorioallantoic membrane. Vessel density of the control and angiotensinogen-treated areas was quantitated by using Sambucus nigra lectin, a specific endothelial cell marker. After 48 h of angiotensinogen treatment by either applying purified angiotensinogen or angiotensinogen-producing Chinese hamster ovary cells, there was a 70% decrease in mesodermic vessel density in comparison to the control sections. Angiotensinogen treatment induced a strong decrease in endothelial cell proliferation of the chorioallantoic membrane vasculature, as shown by incorporation of bromo-deoxyuridine. Two days after local angiotensinogen treatment, increased apoptosis of endothelial cells of mesodermal blood vessels was detected by transferase-mediated deoxyuridine triphosphate nick end labeling assay. As assessed by in situ hybridization, the gene expression pattern of the main vascular growth factors and their receptors was not altered by angiotensinogen. Angiotensinogen, therefore, impairs angiogenesis without altering the expression level of vascular growth factors through the induction of apoptosis and decreased endothelial cell proliferation.Journal of Molecular Medicine 06/2007; 85(5):451-60. · 4.77 Impact Factor
- [show abstract] [hide abstract]
ABSTRACT: The cJun N-terminal kinase 1 (JNK1) is implicated in diet-induced obesity. Indeed, germline ablation of the murine Jnk1 gene prevents diet-induced obesity. Here we demonstrate that selective deficiency of JNK1 in the murine nervous system is sufficient to suppress diet-induced obesity. The failure to increase body mass is mediated, in part, by increased energy expenditure that is associated with activation of the hypothalamic-pituitary-thyroid axis. Disruption of thyroid hormone function prevents the effects of nervous system JNK1 deficiency on body mass. These data demonstrate that the hypothalamic-pituitary-thyroid axis represents an important target of metabolic signaling by JNK1.Genes & development 02/2010; 24(3):256-64. · 12.08 Impact Factor