The β 3 -adrenergic receptor is dispensable for browning of adipose tissues

• Published in: American journal of physiology: endocrinology and metabolism Vol. 312; no. 6; p. E508
• Main Authors: de Jong, Jasper M A, Wouters, René T F, Boulet, Nathalie, Cannon, Barbara, Nedergaard, Jan, Petrovic, Natasa
• Format: Journal Article
• Language: English
• Published: United States 01-06-2017
• Subjects: Adipogenesis - drug effects; Adipose Tissue, Beige - cytology; Adipose Tissue, Beige - drug effects; Adipose Tissue, Beige - metabolism; Adipose Tissue, Brown - cytology; Adipose Tissue, Brown - drug effects; Adipose Tissue, Brown - metabolism; Adrenergic beta-3 Receptor Agonists - pharmacology; Animals; Cold-Shock Response - drug effects; Dioxoles - pharmacology; Female; Gene Expression Regulation - drug effects; Intra-Abdominal Fat - cytology; Intra-Abdominal Fat - drug effects; Intra-Abdominal Fat - metabolism; Male; Mice; Mice, Knockout; Receptors, Adrenergic, beta-1 - genetics; Receptors, Adrenergic, beta-1 - metabolism; Receptors, Adrenergic, beta-3 - chemistry; Receptors, Adrenergic, beta-3 - genetics; Receptors, Adrenergic, beta-3 - metabolism; Reproducibility of Results; RNA, Messenger - metabolism; Signal Transduction - drug effects; Species Specificity; Time Factors; UCP1; brite/beige adipocytes; β3-adrenergic receptor; brown adipocytes; adipose browning
• ISSN: 1522-1555
• DOI: 10.1152/ajpendo.00437.2016

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 β
-adrenergic receptor knockout mice reported that brite/beige adipocytes, but not classical brown adipocytes, require the β
-adrenergic receptor for cold-induced transcriptional activation of thermogenic genes. We aimed to further characterize this requirement of the β
-adrenergic receptor as a functional distinction between classical brown and brite/beige adipocytes. However, when comparing wild-type and β
-adrenergic receptor knockout mice, we observed no differences in cold-induced thermogenic gene expression (
,
,
, and
) 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 β
-adrenergic receptor. Experiments with the β
-adrenergic receptor agonist CL-316,243 verified the functional absence of β
-adrenergic signaling in these knockout mice. The β
-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 β
-adrenergic receptor is dispensable for cold-induced transcriptional activation in both classical brown and, as opposed to earlier studies, brite/beige cells.