Overexpression of leptin in transgenic mice leads to decreased basal lipolysis, PKA activity, and perilipin levels.
Transgenic mice overexpressing leptin (LepTg) exhibit substantial reductions in adipose mass. Since the binding of leptin to its receptor activates the sympathetic nervous system, we reasoned that the lean state of the LepTg mice could be caused by chronic lipolysis. Instead, the LepTg mice exhibited a low basal lipolysis state and their lean phenotype was not dependent on the presence of beta3-adrenergic receptors. In their white adipose tissue, protein levels of protein kinase A, hormone-sensitive lipase, and ADRP were not impaired. However, compared to normal mice, perilipin, perilipin mRNA, and cAMP-stimulated PKA activity were significantly attenuated. Overall, we demonstrate that the lean phenotype of the LepTg mice does not result in a chronically elevated lipolytic state, but instead in a low basal lipolysis state characterized by a decrease in perilipin and PKA activity in white fat.
Ke
Yaohuang
Y
Department of Laboratory Medicine, 505 Parnassus Avenue, University of California, San Francisco, CA 94143-0134, USA.
Qiu
Jun
J
Ogus
Scott
S
Shen
Wen-Jun
WJ
Kraemer
Fredric B
FB
Chehab
Farid F
FF
D000273:Adipose Tissue / Q000378:metabolism*; D000375:Aging / Q000502:physiology; D000818:Animals; D001835:Body Weight / Q000502:physiology; D002352:Carrier Proteins; D000242:Cyclic AMP / Q000378:metabolism*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D004789:Enzyme Activation; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology; D005990:Glycerol / Q000097:blood; D020738:Leptin / Q000378:metabolism*; D008066:Lipolysis / Q000502:physiology*; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D000070778:Perilipin-1; D000070780:Perilipin-2; D010750:Phosphoproteins / Q000378:metabolism*; D022702:Receptors, Adrenergic, beta-3 / Q000378:metabolism; D054411:Receptors, Leptin; D012737:Sex Factors; D015398:Signal Transduction / Q000502:physiology*
D002352:Carrier Proteins; D005230:Fatty Acids, Nonesterified; D020738:Leptin; D008565:Membrane Proteins; D000070778:Perilipin-1; D000070780:Perilipin-2; D010750:Phosphoproteins; C000602983:Plin2 protein, mouse; D022702:Receptors, Adrenergic, beta-3; D054411:Receptors, Leptin; C515447:leptin receptor, mouse; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D005990:Glycerol