1. Augmented expression and secretion of adipose-derived pigment epithelium-derived factor does not alter local angiogenesis or contribute to the development of systemic metabolic derangements.
- Author
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Lakeland TV, Borg ML, Matzaris M, Abdelkader A, Evans RG, and Watt MJ
- Subjects
- Adipose Tissue, White blood supply, Adipose Tissue, White growth & development, Animals, Blood Glucose analysis, Carrier Proteins metabolism, Cell Hypoxia, Diet, High-Fat adverse effects, Eye Proteins blood, Eye Proteins genetics, Humans, Insulin blood, Lipase metabolism, Lipolysis, Male, Mice, Mice, Transgenic, Nerve Growth Factors blood, Nerve Growth Factors genetics, Obesity blood, Obesity etiology, Obesity metabolism, Perilipin-1, Phosphoproteins metabolism, Recombinant Proteins blood, Recombinant Proteins metabolism, Serpins blood, Serpins genetics, Weight Gain, Adipose Tissue, White metabolism, Adiposity, Eye Proteins metabolism, Insulin Resistance, Lipid Metabolism, Neovascularization, Physiologic, Nerve Growth Factors metabolism, Serpins metabolism, Up-Regulation
- Abstract
Impaired coupling of adipose tissue expansion and vascularization is proposed to lead to adipocyte hypoxia and inflammation, which in turn contributes to systemic metabolic derangements. Pigment epithelium-derived factor (PEDF) is a powerful antiangiogenic factor that is secreted by adipocytes, elevated in obesity, and implicated in the development of insulin resistance. We explored the angiogenic and metabolic role of adipose-derived PEDF through in vivo studies of mice with overexpression of PEDF in adipocytes (PEDF-aP2). PEDF expression in white adipocytes and PEDF secretion from adipose tissue was increased in transgenic mice, but circulating levels of PEDF were not increased. Overexpression of PEDF did not alter vascularization, the partial pressure of O2, cellular hypoxia, or gene expression of inflammatory markers in adipose tissue. Energy expenditure and metabolic substrate utilization, body mass, and adiposity were not altered in PEDF-aP2 mice. Whole body glycemic control was normal as assessed by glucose and insulin tolerance tests, and adipocyte-specific glucose uptake was unaffected by PEDF overexpression. Adipocyte lipolysis was increased in PEDF-aP2 mice and associated with increased adipose triglyceride lipase and decreased perilipin 1 expression. Experiments conducted in mice rendered obese by high-fat feeding showed no differences between PEDF-aP2 and wild-type mice for body mass, adiposity, whole body energy expenditure, glucose tolerance, or adipose tissue oxygenation. Together, these data indicate that adipocyte-generated PEDF enhances lipolysis but question the role of PEDF as a major antiangiogenic or proinflammatory mediator in adipose tissue in vivo., (Copyright © 2014 the American Physiological Society.)
- Published
- 2014
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