Activation of the sympathetic nervous system suppresses mouse white adipose tissue hyperplasia through the β1 adrenergic receptor

Adipose tissue (AT) expands via both hypertrophy and hyperplasia during the development of obesity. While AT hypertrophy involves the increase in size of existing adipocytes, hyperplasia is the process of creating new adipocytes from the pool of adipocyte precursor cells (APCs), which includes adipocyte progenitor cells and preadipocytes. Prior studies have implicated a role of the sympathetic nervous system (SNS) in regulation of hyperplasia in white adipose tissue (WAT). Here, we aimed to determine the mechanisms underlying SNS regulation of APC proliferation in mouse WAT. Using flow cytometry with antibodies against various cell surface markers, along with an intracellular marker of proliferation (Ki67), we quantitated the percentages and proliferative status of adipocyte progenitor cells and preadipocytes in the stromal vascular fraction (SVF) of WAT. In vivo SNS activation through cold exposure, as well as in vitro adrenergic stimulation via exposure to the canonical SNS neurotransmitter norepinephrine (NE), inhibited preadipocyte proliferation. Pretreatment with propranolol, a β1- and β2-adrenergic receptor (AR) antagonist, trended toward rescuing the inhibitory effects of NE in primary cell culture. The selective β1-AR agonist dobutamine diminished preadipocyte proliferation both in vivo and in vitro, whereas the selective β2-AR agonist, salbutamol, promoted proliferation in vitro, suggesting that the β1-AR may mediate the inhibitory effect of NE on preadipocyte proliferation. Taken together, we conclude that SNS activation suppresses preadipocyte proliferation via activation of the β1 AR in WAT.