Noradrenergic stimulation of mitochondriogenesis in brown adipocytes differentiating in culture

The ability of adrenergic agents to promote the differentiation and especially the mitochondriogenesis of brown fat precursor cells, grown in culture, was investigated. These cells begin to differentiate during the days preceding confluence. We found here that, already during the early growth phase, the cultures (essentially precursor cells and preadipocytes at this stage) show increased cyclic AMP (cAMP) levels when acutely stimulated with norepinephrine (NE). The cultured cells were therefore chronically treated with NE up to the time of confluence, and their cytochrome-c oxidase activity was measured as an index of mitochondriogenesis. Chronic NE treatment resulted in an increased cytochrome-c oxidase activity of the cells at confluence. This effect was reproduced by selective activation of adenylate cyclase with cholera toxin, suggesting that the NE effect was exerted through an increase in cAMP. Ascorbate (added with NE as an antioxidant) had in itself a positive effect, both on final cell number and on cytochrome-c oxidase activity. It is concluded that NE, working through beta-adrenergic receptors, can stimulate mitochondriogenesis in brown fat cells through a direct effect on the cells, in accordance with the suggestion (based on in vivo experiments) that NE accelerates, rather than initiates, the differentiation process.