Effect of the β3-adrenergic agonist Cl316,243 on functional differentiation of white and brown adipocytes in primary cell culture

AbstractWe investigated the effect of the specific β3-adrenergic receptor agonist CL 316,243 (CL) on proliferation and functional differentiation of the Siberian hamster (Phodopus sungorus) white and brown preadipocytes in primary cell culture. Proliferation of both white and brown preadipocytes was stimulated by a general β-adrenergic agonist (isoproterenol) but not by CL. Lipolysis of differentiated white and brown adipocytes was stimulated similarly by CL with maximum effect at 10 nM. Thermogenic properties of cells were assessed by immunodetection of UCP-1, the brown adipocyte specific uncoupling protein, and measurement of cytochrome c oxidase (COx) activity as an index of mitochondrial capacity. UCP-1 content was largely increased by CL in BAT but not in WAT cultures. Basal UCP-2 mRNA levels were similar in WAT and BAT cultures and increased by both CL and isoproterenol. COx activity of BAT cultures was twice as high as that of WAT cultures but in neither cell culture system could it be increased by β-adrenergic stimulation. We suggest (i) that white and brown preadipocyte proliferation is increased in vitro via β1 or β2, but not β3-adrenergic pathways, (ii) that white and brown preadipocytes represent different cell types, and (iii) that in vitro β-adrenergic stimulation it is not sufficient to induce complete thermogenic adaptation of brown adipocytes