Effect of Obesity on Growth‐related Oncogene Factor‐α, Thrombopoietin, and Tissue Inhibitor Metalloproteinase‐1 Serum Levels

Maury, Eléonore; Brichard, Sonia; Pataky, Zoltan; Carpentier, Anne; Golay, Alain; Bobbioni-Harsch, Elisabetta

doi:10.1038/oby.2009.464

Cited by 36 publications

(26 citation statements)

References 42 publications

(49 reference statements)

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“…RANTES could also be implicated in type 2 diabetes development (15). We have shown previously that the megakaryocytic growth factor TPO was oversecreted by omental adipose tissue of obese subjects (25) and that its circulating levels were increased in obesity and negatively correlated with adiponectinemia (24). Herein, we extend those data by demonstrating that TPO is unambiguously regulated in adipocytes by ApN excess or deficiency in vivo.…”

Section: Discussionsupporting

confidence: 65%

Adipokines identified as new downstream targets for adiponectin: lessons from adiponectin-overexpressing or -deficient mice

Ge¹,

Ryken²,

Noël³

et al. 2011

American Journal of Physiology-Endocrinology and Metabolism

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Adipokines play a central role in the pathogenesis of the metabolic syndrome. Among them, adiponectin (ApN), a master regulator of immune and fuel homeostasis, is decreased. Identifying downstream adipokines targeted by ApN may help in deciphering this syndrome. We have generated transgenic mice, allowing persistent and moderate overexpression of ApN (ApNOverex) specifically in white adipose tissue (AT). We took advantage of this model to unravel the adipokine secretion profile triggered by ApN. AT was fractionated into adipocytes and stromal-vascular cells (SVC), which were cultured for 8 h. Profiling of secretory products by antibody arrays and subsequent ELISAs showed that the secretion of three proinflammatory factors (IL-17B, IL-21, TNF␣) and three hematopoietic growth factors [GF; thrombopoietin and granulocyte (macrophage) colony-stimulating-factors] was reduced in adipocytes of ApN-Overex mice compared with wild-type mice. In the SVC of these mice, besides the hematopoietic GFs, the secretion of another GF (vascular endothelial GF receptor 1), two chemokines (RANTES and ICAM-1), and two proinflammatory factors (IL-6 and IL-12p70) was reduced as well. Only one cytokine, IL-1 receptor 4, was oversecreted by SVC of ApN-Overex mice, which may exhibit antiinflammatory properties. Most of these changes in secretion were due to corresponding changes in mRNAs. A reverse profile of adipokine expression was observed in ApN-KO mice. In conclusion, ApN regulates in vivo the secretion of downstream adipokines, thereby inducing a shift of the immune balance in both adipocytes and SVC toward a less inflammatory phenotype. These downstream adipokines may be new therapeutic targets for the management of the metabolic syndrome.inflammation; adipocytes; stromal-vascular cells; secretome ADIPOSE TISSUE (AT) secretes a number of bioactive peptides, collectively named adipokines. They may exert endocrine actions on distant organs or autocrine/paracrine actions on AT. They play a central role in energy and vascular homeostasis as well as in immunity (23). Virtually all known adipokines are dysregulated in obesity, type 2 diabetes, and metabolic syndrome, leading to overproduction of deleterious adipokines and hyposecretion of defensive ones such as adiponectin (ApN). Such a dysregulation triggers the development of a low-grade proinflammatory state, which is considered to build the common soil for the development of obesity-linked disorders (23).Resetting the immunological balance in adipose tissue may be a crucial approach for the future management of the metabolic syndrome. Adipokines may be potential therapeutic targets.ApN has emerged as a master regulator of immune/inflammatory and fuel homeostasis (14). Besides its vascular protection (32), ApN exerts anti-inflammatory effects on other organs such as liver, colon, cardiac, or skeletal muscles (2,18,30,37). As yet, the autocrine and paracrine anti-inflammatory effects of ApN on its own production site have been scarcely described (1, 9, 22). Moreover, its effects on AT se...

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Section: Discussionsupporting

confidence: 65%

Adipokines identified as new downstream targets for adiponectin: lessons from adiponectin-overexpressing or -deficient mice

Ge¹,

Ryken²,

Noël³

et al. 2011

American Journal of Physiology-Endocrinology and Metabolism

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“…Platelet lifespan is known to be shorter in patients with insulin resistance [25]. Circulating TPO level involved in hyperglycemia, hyperinsulinemia, and insulin resistance, resulting enhanced platelet activation [26]. In the present study, central obesity and HOMA-IR were closely related to platelet count in children and adolescents.…”

Section: Discussionmentioning

confidence: 85%

The association between platelet count and metabolic syndrome in children and adolescents

et al. 2014

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“…21,22 Furthermore, it has been shown that MMPs and TIMPs levels are altered in situations of insulin resistance. 34,35 However, mechanisms involved in these alterations and the protective effects of metformin herein remain to be determined. Taken together, these data suggest that metformin at least in part protected the liver from the onset of fructose-induced steatosis through maintaining intestinal barrier function.…”

Section: Discussionmentioning

confidence: 99%

Metformin protects against the development of fructose-induced steatosis in mice: role of the intestinal barrier function

Spruss

Kanuri

Stahl

et al. 2012

Laboratory Investigation

141

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To test the hypothesis that metformin protects against fructose-induced steatosis, and if so, to elucidate underlying mechanisms, C57BL/6J mice were either fed 30% fructose solution or plain water for 8 weeks. Some of the animals were concomitantly treated with metformin (300 mg/kg body weight/day) in the drinking solution. While chronic consumption of 30% fructose solution caused a significant increase in hepatic triglyceride accumulation and plasma alanineaminotransferase levels, this effect of fructose was markedly attenuated in fructose-fed mice concomitantly treatment with metformin. The protective effects of the metformin treatment on the onset of fructose-induced non-alcoholic fatty liver disease (NAFLD) were associated with a protection against the loss of the tight junction proteins occludin and zonula occludens 1 in the duodenum of fructose-fed mice and the increased translocation of bacterial endotoxin found in mice only fed with fructose. In line with these findings, in metformin-treated fructose-fed animals, hepatic expression of genes of the toll-like receptor-4-dependent signalling cascade as well as the plasminogen-activator inhibitor/cMet-regulated lipid export were almost at the level of controls. Taken together, these data suggest that metformin not only protects the liver from the onset of fructose-induced NAFLD through mechanisms involving its direct effects on hepatic insulin signalling but rather through altering intestinal permeability and subsequently the endotoxin-dependent activation of hepatic Kupffer cells.

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Effect of Obesity on Growth‐related Oncogene Factor‐α, Thrombopoietin, and Tissue Inhibitor Metalloproteinase‐1 Serum Levels

Cited by 36 publications

References 42 publications

Adipokines identified as new downstream targets for adiponectin: lessons from adiponectin-overexpressing or -deficient mice

Adipokines identified as new downstream targets for adiponectin: lessons from adiponectin-overexpressing or -deficient mice

The association between platelet count and metabolic syndrome in children and adolescents

Metformin protects against the development of fructose-induced steatosis in mice: role of the intestinal barrier function

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