Table 1: Several browning agents (genes, microRNAs, and pharmacological, chemical, or plant-based products) that induce browning/browning in adipose tissue and provide protection from HFD-induced obesity.

Browning agentsEffect on browning and metabolic outcomeReference

Gain of function/overexpression
Ucp1Less lipid accumulation in adipocytes, resistance to HFD-induced obesity, beige cell phenotype in WAT, atrophy of BAT, and reduced Ucp1 and mitochondrial DNA content in BAT[38, 39]
Prdm16Beige adipocyte induction in WAT when stimulated by b-AR, increased energy expenditure, limited weight gain, and improved glucose tolerance in response to a HFD[40]
Cox2Ucp1 induction in WAT via stimulation of β-AR, increased thermogenesis, attenuated weight loss and energy expenditure, and protection against HFD-induced obesity[44, 45]
LXA4Higher LXA4 levels were related to browning of WAT, leaner body type, increased energy expenditure, and increased thermogenesis[46, 47]
Foxc2Increased b-AR-cAMP-PKA signaling was associated with reduced fat mass and browning of WAT and protection against HFD-induced obesity[48]
PtenBAT in Pten-overexpressing mice had high levels of Ucp1 and increased energy expenditure[49]
AM2Overexpression in adipose tissue led to reduced acetylation of Pgc1α and favorable interaction between Pgc1α, Prdm16, and Ucp1 in adipocytes, induction of browning in WAT, and protection against HFD-induced obesity[52]

Loss of function/knockdown
BMP7Absence of BMP7 led to reduced interscapular BAT at birth[53, 54]
Smad3/TgfbImproved glucose homeostasis with induction of beige cells in WAT which provided protection against obesity and increased mitochondrial bioenergetic profile of WAT[56]
ABHD6Increased energy expenditure, cold-induced thermogenesis, Ucp1 expression in WAT, fatty acid oxidation, browning of WAT, protection against HFD-induced obesity, and associated complications[58]
GaActivation of Gα signaling abrogates brown adipogenesis, whereas expression of Gα signaling is inversely correlated with Ucp1 expression in WAT
FolliculinMitochondrial uncoupling proteins as well as other markers of brown fat are upregulated in both white and brown FLCN-null adipose tissues[51]
IEX-1Induced browning of WAT, enhanced thermogenesis with markedly less weight gain, and increased energy expenditure on HFD[59]
LXRInduction of beige adipocytes in WAT of mice fed a normal diet with improved metabolic phenotype[60]

MicroRNAs and browning
miR-455Expressed in BAT-specific manner, induced by cold exposure, and induced browning in subcutaneous fat upon cold exposure[64]
miR-92aInversely correlated with BAT activity in humans and could be used as a potential biomarker for BAT activity in mice and humans[65]

Pharmacological and plant-based browning agents
CL 316243β3AR agonist induces browning in WAT, strong response to cold in the form of increased thermogenesis, increased Ucp1 mRNA in WAT and BAT upon treatment, weight loss, and improved energy expenditure[6669]
GleevecIncreased browning of WAT and rate of energy expenditure, acting by blocking PPARg phosphorylation[70]
AcetateIncreased heat production from brown and beige adipocytes corroborated by increased Ucp1 and Prdm16 expression in WAT[71]
TZDsTransforming WAT into BAT-like tissue with increased angiogenesis[72]
PGE2Browning induction in WAT with improved angiogenesis[72]
Slit2 derived secretory productActing via Prdm16 to regulate beige adipocyte induction, increasing Ucp1 expression, and promoting adipose thermogenesis resulting in increased energy expenditure[61]
ButyrateIncreased expression of Ucp-1 and Pgc1α and protected high fat diet-induced obesity in mice[73]
RapamycinβAR-dependent increase in Ucp1 expression and expansion of beige adipocyte in WAT[62]

Plant-based browning agents
ButeinUcp1 induction in WAT, mediated through Prdm4, leads to increased energy expenditure and stimulates generation of thermogenic adipocytes[74]
ResveratrolReducing adipose tissue inflammation and increased expression of genes associated with the browning of adipose tissue[75]
-LapachoneStimulating the browning of WAT, increased expression of BAT-specific genes, decreased body weight gain, and ameliorated HFD effects[76]
CapsaicinActing via TRPV1 channel, increased the expression of Pgc1 and Prdm16 and induced browning in adipose tissue, and provided protection from HFD-induced obesity[77]