Leptin Stimulates Ischemia-Induced Retinal Neovascularization

Suganami, Eri; Takagi, Hitoshi; Ohashi, Hirokazu; Suzuma, Kiyoshi; Suzuma, Izumi; Oh, Hideyasu; Watanabe, Dai; Ojima, T.; Suganami, Takayoshi; Fujio, Yasushi; Nakao, Kazuwa; Ogawa, Yoshihiro; Yoshimura, Nagahisa

doi:10.2337/diabetes.53.9.2443

Cited by 130 publications

(99 citation statements)

References 31 publications

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“…Interaction of leptin with its receptor on endothelial cells leads to activation of the Stat3 pathway and enhancement of its DNA binding activity (SierraHonigmann et al, 1998). Besides a direct proangiogenic activity, leptin upregulates VEGF expression via activation of the Jak/Stat3 signaling pathway (Suganami et al, 2004). Similar to VEGF-A, leptin induces the formation of fenestrated capillaries, as confirmed by the absence of fenestrations in leptin deficient ob/ob mice.…”

Section: Leptinmentioning

confidence: 75%

Angiogenesis and development of adipose tissue

Christiaens

Lijnen

2010

Molecular and Cellular Endocrinology

192

159

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Section: Leptinmentioning

confidence: 75%

Angiogenesis and development of adipose tissue

Christiaens

Lijnen

2010

Molecular and Cellular Endocrinology

192

159

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“…19 Primers used were listed in Table I (available online at http://atvb.ahajournals.org.). Levels of mRNA were normalized to those of 36B4 mRNA.…”

Section: Quantitative Real-time Polymerase Chain Reactionmentioning

confidence: 99%

A Paracrine Loop Between Adipocytes and Macrophages Aggravates Inflammatory Changes

Suganami

Nishida

Ogawa

2005

ATVB

Self Cite

947

809

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Objective-Weight gain is associated with infiltration of fat by macrophages, suggesting that they are an important source of inflammation in obese adipose tissue. Here we developed an in vitro coculture system composed of adipocytes and macrophages and examined the molecular mechanism whereby these cells communicate. Methods and Results-Coculture of differentiated 3T3-L1 adipocytes and macrophage cell line RAW264 results in the marked upregulation of proinflammatory cytokines, such as tumor necrosis factor ␣ (TNF-␣), and the downregulation of the antiinflammatory cytokine adiponectin. Such inflammatory changes are induced by the coculture without direct contact, suggesting the role of soluble factors. A neutralizing antibody to TNF-␣, which occurs mostly in macrophages, inhibits the inflammatory changes in 3T3-L1, suggesting that TNF-␣ is a major macrophage-derived mediator of inflammation in adipocytes. Conversely, free fatty acids (FFAs) may be important adipocyte-derived mediators of inflammation in macrophages, because the production of TNF-␣ in RAW264 is markedly increased by palmitate, a major FFA released from 3T3-L1. The inflammatory changes in the coculture are augmented by use of either hypertrophied 3T3-L1 or adipose stromal vascular fraction obtained from obese ob/ob mice. Key Words: macrophage Ⅲ adipocyte Ⅲ fatty acids Ⅲ TNF-␣ Ⅲ obesity T he metabolic syndrome is a constellation of visceral fat obesity, impaired glucose metabolism, atherogenic dyslipidemia, and blood pressure elevation, which all independently increase a risk of atherosclerotic diseases, such as ischemic heart disease and cerebral stroke. 1,2 The molecular basis for the clustering of such independent risks of atherosclerosis has not fully been elucidated, with visceral fat obesity considered most important. 3,4 Systemic insulin resistance has been implicated as one possible factor that links visceral fat obesity and the adverse metabolic consequences. 4,5 Evidence has accumulated indicating that obesity is associated with a state of chronic, low-grade inflammation, suggesting that inflammation may be a potential mechanism whereby obesity leads to insulin resistance. 5,6 Indeed, obesity and insulin resistance are strongly associated with systemic markers of inflammation, and, clinically, inflammation has been recognized as a major predictor of atherosclerotic disease. [5][6][7] Conclusions-We See coverThe adipose tissue is an important endocrine organ that secretes many biologically active substances, such as leptin, adiponectin, tumor necrosis factor ␣ (TNF-␣), and monocyte chemoattractant protein 1 (MCP-1), which are collectively termed adipocytokines. 4,8 -10 Dysregulated production of proinflammatory and antiinflammatory adipocytokines seen in visceral fat obesity is associated with the metabolic syndrome, 4,6 suggesting that inflammatory changes within the adipose tissue may critically contribute to the development of many aspects of the metabolic syndrome and results in diabetes and atherosclerosis. For example, it has bee...

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“…Growth factors, which are now known to participate in cell division, migration, differentiation, and enzyme production, are also important regulators of wound angiogenesis 9,10 . Consequently, intense interest is now focused on the pharmacological application of angiogenic growth factors in the compromised wound 8,11,12,13,14,15 .…”

Section: Introductionmentioning

confidence: 99%

Burn wound angiogenesis is increased by exogenously administered recombinant leptin in rats

et al. 2008

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Background: Leptin is a potent direct angiogenic factor that stimulates endothelial cell migration and activation in vitro and angiogenesis in vivo. In addition, leptin has been discussed to play an important role in angiogenesis, as it promotes the formation of new blood vessels. Purpose: The effect of exogenously administered leptin on the healing process of a full tissue burn wound model. Methods: Sixty-three Sprague-Dawley male rats were used. Full tissue burn wound was created by electrocautery. The width of the pin was 0.3 cm; its length was 2 cm and was used at the "cut" modulation. Rats were divided into seven groups of nine animals each. Burn wounds were injected with murine recombinant leptin and the rats were sacrificed 3, 7 and 9 days after surgery. Every group had obtained three animals for the three different days of sacrifice. Three different leptin doses of 250 pg/ml, 500 pg/ml and 1000 pg/ml were used in different animal groups (A, B and C). For every one of the three leptin doses used, another animal group was evaluated by using the combined injection of leptin and antileptin (A1, B1, and C1), in order to study the inhibitory effect to the leptin factor. Nine rats were served as controls. These were injected with 0.3 ml water for injection solution and sacrificed at the same time intervals. After sacrifice of the animals, the skin was grossly determined by its appearance, colour and texture. Full thickness burn wounds were dissected for histological examination. A qualitative analysis of angiogenesis in the burn wound was conducted following a standard hematoxylin and eosin stain. The wound tissue samples from each experimental group underwent immunohistochemical evaluation of microvessel density by endothelial cell staining with mouse anti-rat CD 34 monoclonal antibody. Results: The most impressive growth of new blood vessels appeared seven and nine days after treatment with the highest leptin doses. There were no significant differences in microvessel density between the seventh and the ninth postoperative day among different groups treated with leptin. All wounds from the control group, as well as those from animal groups treated with the combined injection of leptin and antileptin did not develop any new vessels. Conclusion: Exogenous administration of recombinant leptin increases early tissue angiogenesis in the burn wound level of an experimental animal model.

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Leptin Stimulates Ischemia-Induced Retinal Neovascularization

Cited by 130 publications

References 31 publications

Angiogenesis and development of adipose tissue

Angiogenesis and development of adipose tissue

A Paracrine Loop Between Adipocytes and Macrophages Aggravates Inflammatory Changes

Burn wound angiogenesis is increased by exogenously administered recombinant leptin in rats

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