Processing of the lipid-mobilizing peptide beta-lipotropin in rabbit adipose tissue.
beta-Lipotropin, a pituitary peptide, is a strong stimulator of lipolysis in rabbit adipose tissue. This polypeptide is shown to be degraded by intact fat pads, homogenized adipose tissue and adipocytes of the rabbit dependent on the amount of adipose tissue, time and the pH of the incubation medium. In subcellular fractions of rabbit adipocytes the proteolytic activity could be localized into the cytosol and the microsomal fraction. To obtain information about the processing of beta-lipotropin in its target cell lipolysis and degradation of this polypeptide were investigated in the presence of inhibitors of distinct cellular mechanisms and in different physiological states such as obesity and starvation. Thus, the stronger lipolytic response in adipocytes from obese rabbits respectively animals fed ad libitum was accompanied by a significantly increased degradation in comparison to lean respectively starved rabbits. The six lysosomotropic agents (chloroquine, NH4Cl, propranolol, quinacrine, acridine orange and tetracaine), the proteinase inhibitors alpha 2-macroglobulin and monodansylcadaverine, cellular ATP depletion by 2-deoxy-D-glucose and 2,4-dinitrophenol and the omission of Ca2+ ions from the incubation medium inhibited dose-dependently the lipolytic activity as well as the degradation of beta-lipotropin in intact and homogenized adipose tissue. Inhibitors of the cytoskeleton such as colchicine, cytochalasin B, vinblastine and concanavalin A also reduced lipolysis but only the degradation in intact adipose tissue. It can be concluded that after receptor-mediated uptake the cytoskeleton and lysosomal proteases are involved in the processing of beta-lipotropin.
Department of Medicine II, University of Munich, F.R.G.
W O
WO
Richter
B G
BG
Jacob
P
P
Schwandt
D000273:Adipose Tissue / Q000378:metabolism*; D000818:Animals; D002478:Cells, Cultured; D003599:Cytoskeleton / Q000187:drug effects / Q000502:physiology; D010450:Endopeptidases / Q000378:metabolism; D005508:Food Deprivation; D008066:Lipolysis / Q000187:drug effects; D008247:Lysosomes / Q000187:drug effects / Q000201:enzymology; D009765:Obesity / Q000378:metabolism; D011817:Rabbits; D013347:Subcellular Fractions / Q000378:metabolism; D008083:beta-Lipotropin / Q000378:metabolism* / Q000494:pharmacology
D008083:beta-Lipotropin; D010450:Endopeptidases