We examined whether the reduction in fat mass induced by EGF treatment in mature animals was via activation of hormone-sensitive lipase (HSL) and thereby the induction of lipolysis, or through inhibition of lipoprotein lipase activity thus reducing fat uptake in adipose tissue. Sixteen male rats were treated with placebo or EGF 150 µg/kg/day for 7 days via mini-osmotic pumps. The results demonstrate that systemic EGF treatment reduces the amount of adipose tissue, most likely due to increased lipolysis as HSL activity as well as HSL mRNA were increased. The circulating levels of free fatty acids were slightly increased and leptin levels reflected the decrease in adipose tissue mass.

Keywords:
Epidermal growth factor, Hormone-sensitive lipase, Lipoprotein lipase, Leptin, Adipose tissue, rat
1.
Prigent SA, Lemoine NR: The type 1 (EGFR-related) family of growth factor receptors and their ligands. Prog Growth Factor Res 1992;4:1–24.
2.
Salomon DS, Brandt R, Ciardiello F, Normanno N: Epidermal growth factor-related peptides and their receptors in human malignancies. Crit Rev Oncol Hematol 1995;19:183–232.
3.
Serrero G, Mills D: Physiological role of epidermal growth factor on adipose tissue development in vivo. Proc Natl Acad Sci USA 1991;88:3912–3916.
4.
Vinter-Jensen L, Flyvbjerg A, Nexø E: Systemic treatment with EGF causes organ growth concomitant with concomitant reduced circulating levels of IGF-I and IGFBP-3. Time-dependent changes in female rats. Growth Regul 1997;7:1–10.
5.
Luetteke NC, Lee DC, Palmiter RD, Brinster RL, Sandgren EP: Regulation of fat and muscle development by transforming growth factor α in transgenic mice and in cultured cells. Cell Growth Differ 1993;4:203–213.
6.
Kurachi H, Adachi H, Ohtsuka S, Morishige K, Amemiya K, Keno Y, Shimomura I, Tokunaga K, Miyake A, Matsuzawa Y, Tanizawa O: Involvement of epidermal growth factor in inducing obesity in ovariectomized mice. Am J Physiol 1993;265:E323–E331.
7.
Adachi H, Kurachi H, Homma H, Adachi K, Imai T, Sakata M, Matsuzawa Y, Miyake A: Involvement of epidermal growth factor in inducing adiposity of aged female mice. J Endocrinol 1995;146:381–393.
8.
Vinter-Jensen L, Juhl CO, Frystyk J, Dajani EZ, Oksbjerg N, Flyvbjerg A: The effect of epidermal growth factor (EGF) on circulating levels of insulin-like growth factor (IGF) and IGF binding proteins (IGFBPs) in adult Göttingen minipigs. J Endocrinol 1996;151:401–407.
9.
Reynisdottir S, Dauzats M, Thorne ALD: Comparison of hormone-sensitive lipase activity in viscerela and subcutaneous human adipose tissue. J Clin Endocrinol Metab 1997;82:4162–4166.
10.
Weinstck PH, Levak-Frank S, Hudgins LC, Radner H, Friedman JM, Zechner R, Breslow JL: Lipoprotein lipase controls fatty acid entry into adipose tissue, but fat mass is preserved by endogenous synthesis in mice deficient in adipose tissue lipoprotein lipase. Proc Natl Acad Sci USA 1997;94:10261–10266.
11.
Tebar F, Ramirez I, Soley M: Epidermal growth factor modulates the lipolytic action of catecholamines in rat adipocytes. Involvement of a Gi protein. J Biol Chem 1993;268:17199–17204.
12.
Prokicimer PG, Maze M, Vickery RG, Kraemer FB, Gandjei R, Hoffman BB: Mechanism of halothane-induced inhibition of isoproterenol-stimulated lipolysis in isolated rat adipocytes. Mol Pharmacol 1988;33:338–343.
13.
Pessin JE, Gitomer W, Oka Y, Oppenheimer CL, Czech MP: β-Adrenergic regulation of insulin and epidermal growth factor receptors in rat adipocytes. J Biol Chem 1983;258:7386–7394.
14.
Anthonsen MW, Ronnstrand L, Wernsedt C, Degermann E, Holm C: Identification of novel phosphorylation sites in hormone-sensitive lipase that are phosphorylated in response to isoproterenol and govern activation properties in vitro. J Biol Chem 1998;273:215–221.
15.
Haysted AJ, Hardie DG: Both insulin and epidermal growth factor stimulate lipogenesis and acetyl-coA carboxylase activity in isolated adipocytes. Biochem J 1986;234:279–284.
16.
Adachi H, Kurachi H, Homma H, Adachi K, Imai T, Morishige K, Matsuzawa Y, Miyake A: Epidermal growth factor promotes adipogenesis of 3T3-L1 cell in vitro. Endocrinology 1994;135:1824–1830.
1999
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