TABLE 2.

Targetable receptors in adipose tissue and their actions and limitations.

Receptor	Beneficial action	Actions on thermogenic adipose tissue	Potential mechanism	Reasons for their limitation
β2/β3-Adrenergic receptors	Agonism	Increase BAT activation; induce beiging	Activate cAMP/PKA signaling; co-express with UCP1	Side effects such as cardiovascular dysfunction
A2A/A2B adenosine receptors	Agonism	Increase BAT activation and induce beiging	Heterodimerization of A2B and A2A receptors	Uncertain
PPARα/β/γ/δ	Agonism	Regulates BAT biology; induces beiging; counters against HFD-induced BAT whitening	Cooperates with PGC-1α and PRDM16; activates the thermogenic pathway and enhances lipolysis; activates fatty acid oxidation	Weight gain effect; side effects such as hepatotoxicity, myocardial infarction, bladder cancer, and heart failure
Glucocorticoid/mineralocorticoid receptors	Antagonism	Prevent HFD-induced lipid accumulation in BAT, decrease fat mass and body weight; induce beiging; enhance BAT function	UCP1 “unmasking”	Antagonism on androgen and progesterone receptors; risk of hyperkalemia
Thyroid hormone receptors	Agonism	Induce beiging and promote adaptive thermogenesis; induce BAT proliferation	Crosstalk between thyroid hormone receptor signaling and β-adrenergic receptor signaling; promote progenitor cell proliferation	Uncertain