The β3-adrenergic receptor is dispensable for browning of adipose tissues

Brown and brite/beige adipocytes are attractive therapeutic targets to treat metabolic diseases. To maximally utilize their functional potential, further understanding is required about their identities and their functional differences. Recent studies with beta(3)-adrenergic receptor knockout mice reported that brite/beige adipocytes, but not classical brown adipocytes, require the beta(3)-adrenergic receptor for cold-induced transcriptional activation of thermogenic genes. We aimed to further characterize this requirement of the beta(3)-adrenergic receptor as a functional distinction between classical brown and brite/beige adipocytes. However, when comparing wild-type and beta(3)-adrenergic receptor knockout mice, we observed no differences in cold-induced thermogenic gene expression (Ucp1, Pgc1a, Dio2, and Cidea) in brown or white (brite/beige) adipose tissues. Irrespective of the duration of the cold exposure or the sex of the mice, we observed no effect of the absence of the beta(3)-adrenergic receptor. Experiments with the beta(3)-adrenergic receptor agonist CL-316,243 verified the functional absence of beta(3)-adrenergic signaling in these knockout mice. The beta(3)-adrenergic receptor knockout model in the present study was maintained on a FVB/N background, whereas earlier reports used C57BL/6 and 129Sv mice. Thus our data imply background-dependent differences in adrenergic signaling mechanisms in response to cold exposure. Nonetheless, the present data indicate that the beta(3)-adrenergic receptor is dispensable for cold-induced transcriptional activation in both classical brown and, as opposed to earlier studies, brite/beige cells.