Flavonoids as inducers of white adipose tissue browning and thermogenesis: signalling pathways and molecular triggers

Zhang, Xuejun; Li, Xin; Fang, Huang; Guo, Fengjin; Li, Feng; Chen, Anmin; Huang, Shilong

doi:10.1186/s12986-019-0370-7

Table 1 Major subclasses of flavonoids with examples and studies on the effects of flavonoids on WAT browning

From: Flavonoids as inducers of white adipose tissue browning and thermogenesis: signalling pathways and molecular triggers

Compound	Source	In vivo/vitro	Dose/Duration	Effect	Ref.
Flavonol
Quercetin	Onion-peel	C57BL/6 mice, 3 T3-L1 adipocytes	5 mg/g diet, 8 W 0-240 μM	AMPK/Sirt1/PGC-1α↑	[24]
Quercetin	Onion peel	HFD-induced metabolic Syndrome	0.8 mg/g diet	Nrf2/HO-1↑, NF-kB↓, attenuated oxidative stress and inflammation	[25]
Quercetin	Onion peel	HFD-fed mice	1 mg/g, 12 W	AMPK /Sirt1 pathway	[26]
Quercetin (Q) and Resveratrol (RSV)		HFD-induced obese Rats	15 + 30 mg/kg 6 W	perirenal WAT and interscapular BAT UCP-1↑	[27]
Quercetin	Onion peel	HFD-fed mice	1 mg/g, 12 W	sWAT browning and TG↓	[28]
Quercetin	Onion peel	3 T3-L1 adipocytes	10, 50, and 100 μM	AMPK pathway, ERK1/2 and JNK phosphorylation	[29]
Isorhamnetin	Metabolite of quercetin	3 T3-L1 adipocyte ob/ob mice	12.5 to 50 μM 10 mg/g, 4 W	PPARγ↓	[30]
Quercetin-rich onion peel extract	Onion peel	3 T3-L1 adipocyte	1to 50 μg/ml	PPARγ and C/EBPα↓, aP2 and LPL↓	[31]
Rutin	Mulberry	Db/Db and HFD-fed mice, C3H10T1/2 cells	1 mg/ml in water, 10 W10 μM	Sirt1/PGC-1α/Τfam↑	[19]
Rutin	Mulberry	HFD-induced obesity C57BL/6 mice	50 mg/kg, 8 W	PGC-1α↑	[32]
Anthocyanins
Cy-3-G		db/db mice	1 mg/ml in water, 16 W	UCP1, Sirt1 and PGC-1α, PPARα	[33]
Cy-3-G	Mulberry	HFC-fed C57BL/6 J mice, C3H10T1/2 clone8 cells	200 mg/kg, 8 W 100, 200 μg/ml	PGC-1α, FGF21, eNAMPT	[34]
Cy-3-G		3 T3-L1 adipocytes	20–100 μM	AMPK, cAMP-C/EBPβ↑	[35]
Mulberry extract Cy-3-G	Mulberry	C3H10T1/2 MSCs	10 μg/ml	p38AMPK–PGC-1α-PRDM16	[36]
Flavan-3-ols
Flavan-3-ol	Cocoa	ICR mice	10 mg/kg diet, 2 to 20 h	AMPK/ PGC-1α↑	[37]
Flavan-3-ol fraction	Cocoa	C57BL/J mice	50 mg/g, 2 W	PGC-1α/UCP-1↑MCAD	[38]
Flavan-3-ol fraction	Cocoa	HFD-fed Wistar rats	2 mg/g diet, 4 W	β-oxidation-related enzymes and UCP-1↑	[39]
Catechins	Tea	HFD-fed SD rats	5 mg/g diet, 5 W	BAT and UCP1↑	[40]
Theaflavins	Black tea	ICR mice	10 ml/kg, 2 to 20 h	AMPK/PGC-1α↑	[41]
Oolong,blackandpu-erh	Tea	ICR mice	2 g/100 ml drink for 7 days	AMPK/UCP-1↑, PPARγ and C/EBPα↓	[42]
Catechins	Green tea	HFD-fed SD rats,	100 mg/kg/d, 30 Days	PPARγ increased in sWAT and decreased in vWAT, PPARδ↑	[43]
Green tea extract	Green tea	SD rats	50 mg/kg, 24 h	NA-cAMP axis	[44]
(−)-epicatechin	Cacao	HFD-fed C57BL/6 mice, Human adipocytes	1 mg/g diet, 15days100nM	Mitochondrial biogenesis and fat browning	[45]
Flavones
Chrysin	Flowers, honeycombs, and mushrooms	3 T3-L1 adipocytes	50 μM	AMPK/PGC-1α/UCP-1	[46]
Luteolin	Pepper, celery, thyme, peppermint	HFD-fed C57BL/6 mice	0.1 mg/g diet, 12 W	AMPK/PGC-1α signaling↑	[20]
Nobiletin	Citrus fruits	3 T3-L1 adipocytes and HIB1B brown adipocytes	100 μM	AMPK/PGC-1α and Sirt1	[47]
Sudachitin	Sudachi	C57BL/6 and db/db mice	5 mg/kg, 4 and 12 weeks	Sirt1–PGC-1α	[48]
Flavanones
G-hesperidin	Peel of fruits	Wistar rats	60 mg/ml in water	BAT-SNA↑, CASNA↓	[49]
Naringenin		HFD-fed Ldlr(−/−) mice	10,30 mg/g, 4 W	PGC-1α/ PPARα	[50]
Citrus aurantium flavonoids	Hesperidin, Naringenin, and Nobiletin	3 T3-L1 adipocytes	0, 10, or 50 μg/ml	Akt/PPARγ and C/EBPα↓	[51]
Naringenin		Long-Evans hooded rats	0.03 to 0.12 mg/g, 6 W	PPARα↑	[52]
Isoflavones
Isoflavones	Soy	Male SD rats	0.5 or 4 g/kg, 2 W	UCP, PPARα↑	[53]
Isoflavones	Soy food products	Long-Evans rats	600 mg/g diet, 33, 55 or 75 days of age	BNP Y↑, Thyroid↑, leptin and insulin↓	[54]
Genistein	Soyabeans	3 T3-L1 adipocytes	100 μM	C/EBPβ, PGC-1α, Sirt1↑	[55]
Daidzein	Soy isoflavones	HFD-fed Rats	50 mg/kg, 2 W	PPARγ and SCD1↓	[56]
Flavonolignan
Silibinin	Milk thistle	Human ACS	10 μM	Sirt1, PPARα, PGC-1α↑	[21]
Proanthocyanidins
Proanthocyanidins	Fruits, berries, beans, nuts, cocoa and wine	Wistar rats fed with a cafeteria diet	25 and 50 mg/kg diet, 4 months	Sirt1 and PGC-1α↑	[57]
Proanthocyanidin extracts	Chinese bayberry	HFD-fed obese SD rat	4, 26, 53%, 4 W	Sirt1, BMP4↑, C/EBP-α, PPAR-γ↓	[58]
Proanthocyanidin		Wistar rats	250 mg/kg	PGC-1α↑	[59]
Flavangenol	French martima pine bark	HFD-fed Wister rats	3 μg intraduodenal injection, 60 min	BAT-SNA↑	[60]
Procyanidin	Cacao liquor	HFD-fed C57BL/6 mice	5, 20 mg/g diet, 13 W	AMPKα/GLUT4/ PGC-1α↑	[61]
Xanthohumol
Xanthohumol-rich hop extrac	Humulus lupulus L	3 T3-L1 adipocytes	10, 25 μg/ml	PPAR-γ, C/EBPα, aP2↓	[62]
Xanthohumol	Humulus lupulus L	3 T3-L1 adipocytes	0 to 100 μM	PPAR-γ, C/EBPα, aP2↓, apoptosis↑	[63]
Matured Hop Bittering Components		HFD-fed C57BL/6 J mice Wistar rats	0 to 2 mg/kg, 9 W 2 or 10 mg/kg, 90 min	BAT-SNA, PGC-1α, PRDM16, PPARγ↑	[64]
Plant Extract Mixture
Black soybean seed coat extract	Black soybean	Male C57BL/6 mice	0 to2 mg/g diet 14 weeks	UCP1↑in BAT and WAT; TNF-α and MCP-1↓.	[65]
Extract of kumquat	Citrus fruits	HFD-fed C57BL/6 mice	10 mg/kg, 8 weeks, 3 months	PPARα↑	[66]
Puerariae flower extract	Kudzu flower	HFD-fed C57BL/6 J mice	50 mg/kg, 13.55 mg/kg ISOF, 6 W	UCP1↑in BAT	[67]
Olive Leaf Extract	Oleuropein	Human ASCs	0.27 and 0.37 mg/ml	Sirt1, PPARα, PGC-1α↑	[68]
E. cava polyphenol extract	Brown alga Ecklonia cava	HFD-fed C57BL/6 mice	100, 500 mg/kg/day 12 W	AMPK, PGC-1α, Sirt1↑	[69]

Back to article page

ISSN: 1743-7075

Contact us

General enquiries: journalsubmissions@springernature.com

Nutrition & Metabolism

Contact us