Table 1.
Summary of bioactive compounds that induce white fat browning.
| Classification | Browning agent | Mechanism | Challenges |
|---|---|---|---|
| β3-AR | CL316243 (Cero et al. 2021) | Activation of β3-sympathomimetic activity | Poor oral bioavailability, poor gastrointestinal absorption, and first-pass hepatic destruction, side-effects (such as increased heart rate and blood pressure) |
| Mirabegron (Cero et al. 2021) | Activation of β3-sympathomimetic activity | Cardiovascular side effects | |
| PPARγ agonist | Rosiglitazone (Ohno et al. 2012) | Stabilization of PRDM16 protein | Off-target effects (such as body weight gain, congestive heart failure, bone loss, bone fracture) |
| AMPK agonist | Metformin (Malin and Kashyap 2014) | Activation of AMPK and FGF21 | Low bioavailability, low targeting specificity, gastrointestinal side effects |
| Notch signaling Inhibitor |
DBZ (Bi et al. 2014) | Inhibition of Notch signaling | Off-target effects, large systemic dose requirement, undesired drug accumulation in the liver |
| TH | T3 (López et al. 2010) | Decreased activity of hypothalamic AMPK, increased SNS activity | Multiple deleterious effects (Cardiotoxicity, bone loss, muscle wasting, perturbation of the neuroendocrine circuit), impair thermogenesis in BAT |
| BMPs | BMP7 (Boon et al. 2013) | Sympathetic activation | No targeting specificity, systemic side effects |
| o-3 unsaturated fatty acid | DHA (Zhuang et al. 2019) | Increased mitochondria-mediated β-oxidation | Low enrichment efficiency for adipose tissue, suboptimal bioavailability. easily destroyed by oxidation, low efficacy, unexpected side effects |
| Nitrogen oxides | NO (Dai et al. 2013) | cGMP-dependent pathways and cross-talk with other molecules such as AMPK, PPARγ, PGC-1α | Low bioavailability |
| Natural products | Cap (Baskaran et al. 2016), Res (Qiang et al. 2012), et al. | Activation of TRPV1 channels, Sirt1-dependent deacetylation of PPARγ | Considerable hydrophobicity, low bioavailability, obvious irritation of the mouth and gastrointestinal tract |
Note: PPAR γ: peroxisome proliferator-activated receptor γ; AMPK: Adenosine 5’-monophosphate-activated protein kinase; T3: triiodothyronine; TH: Thyroid hormone; BMPs: Bone morphogenetic proteins; Bmp7: Bone morphogenetic protein 7; β3-AR: β3-adrenergic receptor; TRPV1: transient receptor potential cation channel subfamily V member 1; SIRT1: NAD-dependent deacetylase sirtuin 1; PGC1-α: peroxisome proliferator-activated receptor-gamma coactivator-1α; BAT: brown adipose tissue; PRDM16: PR domain-containing 16; FGF21: Fibroblast growth factor 21; DBZ: Dibenzazepine; DHA: Docosahexaenoic acid; SNS: Sympathetic nervous system; cGMP: Cyclic guanosine monophosphate; TRPV1: transient receptor potential cation channel subfamily V member 1; Cap, Capsaicin; Res, Resveratrol.