Effect of the beta 3-adrenergic agonist Cl316,243 on functional differentiation of white and brown adipocytes in primary cell culture

We investigated the effect of the specific beta (3)-adrenergic receptor ago nist CL 316,243 (CL) on proliferation and functional differentiation of the Siberian hamster (Phodopus sungorus) white and brown preadipocytes in prim ary cell culture. Proliferation of both white and brown preadipocytes was s timulated by a general beta -adrenergic agonist (isoproterenol) but not by CL. Lipolysis of differentiated white and brown adipocytes was stimulated s imilarly by CL with maximum effect at 10 nM. Thermogenic properties of cell s were assessed by immunodetection of UCP-1, the brown adipocyte specific u ncoupling protein, and measurement of cytochrome c oxidase (COx) activity a s an index of mitochondrial capacity. UCP-1 content was largely increased b y CL in BAT but not in WAT cultures. Basal UCP-2 mRNA levels were similar i n WAT and BAT cultures and increased by both CL and isoproterenol. COx acti vity of BAT cultures was twice as high as that of WAT cultures but in neith er cell culture system could it be increased by beta -adrenergic stimulatio n. We suggest (i) that white and brown preadipocyte proliferation is increa sed in vitro via beta (1) or beta (2), but not beta (3)-adrenergic pathways , (ii) that white and brown preadipocytes represent different cell types, a nd (iii) that in vitro beta -adrenergic stimulation it is not sufficient to induce complete thermogenic adaptation of brown adipocytes. (C) 2001 Elsev ier Science B.V. All rights reserved.