Biological Action of Leptin as an Angiogenic Factor

Abstract

Leptin is a hormone that regulates food intake, and its receptor (OB-Rb) is expressed primarily in the hypothalamus. Here, it is shown that OB-Rb is also expressed in human vasculature and in primary cultures of human endothelial cells. In vitro and in vivo assays revealed that leptin has angiogenic activity. In vivo, leptin induced neovascularization in corneas from normal rats but not in corneas from fa/fa Zucker rats, which lack functional leptin receptors. These observations indicate that the vascular endothelium is a target for leptin and suggest a physiological mechanism whereby leptin-induced angiogenesis may facilitate increased energy expenditure.

The effect of a rapid weight loss induced by laparoscopic adjustable gastric banding on arterial stiffness, metabolic and inflammatory parameters in patients with morbid obesity

“…Finally, obesity might increase arterial stiffness through the hormone leptin, which has been shown to promote VSMC proliferation and angiogenesis. 28,29 Obesity is often accompanied by the metabolic syndrome, and substantial improvement of the latter also occurs with weight loss. Interestingly, clinical evidence that improvement of metabolic parameters in obesity reduces vascular stiffening is lacking.…”

Leptin is favourably associated with vascular function in obese Caucasians, but not in obese Africans

“…Indeed, after this adjustment, the associations between leptin and SV, CO and C W disappeared, but a negative association with DBP became apparent and the negative association with TPR remained. These results were confirmed by means of multiple regression analyses (Table 3 What is known about leptin and cardiovascular function (a) Leptin correlates with body fat mass and is invariably elevated in obese compared to lean subjects 6 (b) Leptin has been found to be positively associated with blood pressure in various population groups [8][9][10][11][12][13] (c) Leptin is independently associated with systolic blood pressure, pulse pressure and arterial compliance in obese hypertensive African women 21 (d) Leptin has pressor effects by: K Decreasing vascular function 14 Leptin is independently associated with intima media thickness of the common carotid artery 15 and decreased arterial distensibility, decreasing arterial compliance 14 This is possible since leptin receptors are situated on the endothelium 35 and vascular smooth muscle cells 36 K Increasing renal sympathetic activity:…”

Cellular and molecular mechanisms in liver fibrogenesis

“…Although leptin may stimulate multiple signaling pathways, literature data suggest that its pro-fibrogenic effects are mainly NADPH oxidase and ROS dependent [56] and may also be mediated by inhibition of the expression and activity of peroxisome proliferator-activated receptor- (PPAR-), which maintains HSC quiescence and reverses HSC trans-differentiation to MFs. Recently, leptin has also been shown to modulate liver angiogenesis being able to both exert a direct angiogenic action in vascular endothelial cells [57] and stimulate HSC to increase expression and release of vascular endothelial growth factor A (VEGF-A), which is the most potent pro-angiogenic cytokine [52]. This is relevant because of the emerging evidence indicating that angiogenesis is not only a critical component of chronic wound healing but can indeed favor liver fibrogenesis.…”