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.
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.
Biology of Lipid Metabolism Laboratory, Department of Physiology, Monash University, Clayton, Victoria, Australia.
Thomas V
TV
Lakeland
Biology of Lipid Metabolism Laboratory, Department of Physiology, Monash University, Clayton, Victoria, Australia.
Melissa L
ML
Borg
Biology of Lipid Metabolism Laboratory, Department of Physiology, Monash University, Clayton, Victoria, Australia.
Maria
M
Matzaris
Biology of Lipid Metabolism Laboratory, Department of Physiology, Monash University, Clayton, Victoria, Australia.
Amany
A
Abdelkader
Biology of Lipid Metabolism Laboratory, Department of Physiology, Monash University, Clayton, Victoria, Australia.
Roger G
RG
Evans
Biology of Lipid Metabolism Laboratory, Department of Physiology, Monash University, Clayton, Victoria, Australia matthew.watt@monash.edu.
Matthew J
MJ
Watt
D052436:Adipose Tissue, White / Q000098:blood supply / Q000254:growth & development / Q000378:metabolism*; D050154:Adiposity; D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D002352:Carrier Proteins / Q000378:metabolism; D015687:Cell Hypoxia; D059305:Diet, High-Fat / Q000009:adverse effects; D005136:Eye Proteins / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D008049:Lipase / Q000378:metabolism; D050356:Lipid Metabolism; D008066:Lipolysis; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D018919:Neovascularization, Physiologic; D009414:Nerve Growth Factors / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D009765:Obesity / Q000097:blood / Q000209:etiology / Q000378:metabolism; D000070778:Perilipin-1; D010750:Phosphoproteins / Q000378:metabolism; D011994:Recombinant Proteins / Q000097:blood / Q000378:metabolism; D015843:Serpins / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation; D015430:Weight Gain; D000099174:Pigment Epithelium-Derived Factor; D000217:Acyltransferases
D001786:Blood Glucose; D002352:Carrier Proteins; D005136:Eye Proteins; D007328:Insulin; D008049:Lipase; D009414:Nerve Growth Factors; D000070778:Perilipin-1; D010750:Phosphoproteins; D011994:Recombinant Proteins; D015843:Serpins; D000099174:Pigment Epithelium-Derived Factor; C000602978:PLIN1 protein, human; C000602979:Plin1 protein, mouse; C494445:PNPLA2 protein, mouse; D000217:Acyltransferases
insulin sensitivity; lipolysis; obesity; pigment epithelium-derived factor