Table 3.

In vivo evidence for the increase of non-shivering thermogenesis by flavonoids.

Flavonoids		Subjects	Treatments	Outcomes	Authors
Flavone	Luteolin	Male C57BL/6 mice	HFD with 0.01% luteolin for 12 weeks	↑ O2 consumption and CO2 production ↑ BAT activity ↑ SWAT browning ↑ AMPK/PGC1α signaling	Zhang et al. [33]
	Olive leaf extract (luteolin)	Male C57BL/6N mice	HFD with 0.15% olive leaf extract for 8 weeks	↓ Body weight and fat pad weight ↑ Browning and mitochondrial biogenesis in EWAT	Shen et al. [43]
	Apigenin mixed with naringenin	Male C57BL/6 mice	Apigenin/naringenin (80 mg/kg) for 2 weeks	↑ UCP1 in BAT	Thaiss et al. [46]
	Sudachitin	C57BL/6 J mice and db/db mice	HFD with 5 mg/kg sudachitin for 12 weeks	↓ Body weight, subcutaneous and visceral fat contents ↑ O2 consumption and energy expenditure ↑ Ucp1 in SWAT	Tsutsumi et al. [50]
Flavonol	Onion peel Extract (quercetin)	Male SD rats	HFD with 0.36 and 0.72% onion peel extract for 8 weeks	↓ Body weight and weights of total visceral, retroperitoneal, and mesenteric fat fads ↑ Ucp1 and Cpt1α in EWAT	Moon et al. [52]
	Onion peel extract (quercetin)	Male C57BL/6 mice	HFD with 0.5% onion peel for 8 weeks	↑ Adipocyte browning in RWAT and SWAT	Lee et al. [54]
	Quercetin	Male C57BL/6 mice	HFD with 0.1% Quercetin for 12 weeks	↓ Body weight and weights of EWAT and SWAT ↑ AMPK phosphorylation, and SIRT1 expression in EWAT ↑ Ucp1 in BAT	Dong et al. [53]
	Rutin	Male C57BL/6 J mice and C57BLKS/J-(db/db) mice	HFD with rutin (1 mg/mL) in drinking water for 10 weeks	↑ Mitochondria biogenesis and whole-body energy expenditure ↑ BAT activity and SWAT browning	Yuan et al. [57]
	Rutin	Female polycystic ovary syndrome SD-rats	Rutin (100 mg/kg) in drinking water for 3 weeks	↑ UCP1, Ucp1, Pparα, Pgc1α, Pgc1β, and Cpt1α in BAT, ↑ Body temperature	Hu et al. [60]
	Myricetin	Male C57BLKS/J-(db/db) mice	HFD with myricetin (400 mg/kg) in drinking water for 14 weeks	↓ Body weight, fat mass, and blood glucose ↑ Body temperature and oxygen consumption ↑ BAT activity ↑ IWAT browning and mitochondrial biogenesis	Hu et al. [61]
	Gelidium elegans (hesperidin rich)	Male ICR mice	HFD with Gelidium elegans extract (50, 200 mg/kg/day) for 7 weeks	↓ Body weight, fat mass, plasma insulin, and TG level ↑ AMPK phosphorylation in BAT and BAT activity	Choi et al. [68]
	G-hesperidin	Male Wistar rats	60 mg of G-hesperidin by acute oral administration	↑ BAT-sympathetic nerve activity ↑ Body temperature ↓ Cutaneous sympathetic nerve activity	Shen et al. [70]
Flavanal	Green tea extract (catechin and EGCG)	Male SD rats	Chow diet with catechin and EGCG (0–200 µM) in drinking water	↑ BAT activity and O2 uptake rate	Dulloo et al. [75]
	Green tea (EGCG)	Male SD rats	HFD with green tea extract (20 g/kg)	↓ Body weight, digestibility ↑ Energy expenditure ↑ BAT density and β-adrenoceptor activity	Choo et al. [76]
	Tea catechins (TC)	Male SD rats	Low fat diet (LFD) and HFD with 0.5% TC for 5 weeks	↑ Ucp1 in BAT of LFD with TC group - No significant difference between HF and HF with TC	Nomura et al. [77]
	Green tea catechins	Male SD rats	LFD and HFD with green tea catechins (100 mg/kg) for 5 weeks	↑ PPARδ, UCP1, Ucp1, and CPT1α in WAT and BAT	Yan et al. [78]
	Oolong, black, and pure teas	Male ICR mice	7 days consumption with tea boiled with 2 g tea leaves in 100 mL	↓ Weight of WAT, ↑ AMPK phosphorylation in WAT and BAT, ↑ UCP1 in WAT	Yamashita et al. [82]
	Catechin	Healthy young women	540 mg/day; catechin for 12 weeks	↑ BAT density	Nirengi et al. [84]
	Epigalo catechin gallate (EGCG)	Healthy young men	Cold exposure for 3 h after 1600 mg of EGCG and 600 mg of caffeine intake	↑ Energy expenditure ↓ Shivering thermogenesis	Gosselin et al. [85]
	Cocoa flavanols	Male ICR mice	10 mg/kg cocoa flavonoid fraction or epicatechin.	↑ BAT activity ↑ AMPK phosphorylation in BAT ↑ Plasma catecholamine level	Matsumura et al. [85]
	Cocoa flavanols	Male Wistar rat	HFD with cocoa powder 1 g/kg, cocoa extract 100 mg/kg and (-)-epicatechin 10 mg/kg for 8 weeks	↑ Ucp1, Pparγ, Pparα, Sirt1, and Pgc1α in BAT ↑ AMPK phosphorylation in BAT ↑ Plasma catecholamine level	Rabadan-Chávez et al. [88]
	Epicatechin	Male Wistar rats	HFD for 5 weeks with (-)-epicatechin (1 mg/kg) for additional 2 weeks	↑ EWAT browning ↓ Body weight	Gutiérrez-Salmeán et al. [89]
Anthocyanin	Bilberry Extract	Male KK-Ay mice	27 g/kg diet for 5weeks	↑ AMPK in SWAT and skeletal muscle	Takikawa et al. [96]
	Cyanidin-3-glucoside (C3G)	Male C57BLKS/J-(db/db) mice	C3G dissolved in drinking water (1 mg/mL) for 16 weeks	↑ Energy expenditure representing oxygen consumption ↑ BAT activity ↑ Body temperature and mitochondrial biogenesis in BAT ↑ SWAT browning ↓ Body weight gain, and weight of EWAT and SWAT	You et al. [98]
Isoflavone	Puerariae flower (PFE) and isoflavone fraction (PF)	Male C57BL/6J mice	HFD with 5% PFE and PF isoflavone fraction for 6 weeks	↑ Energy expenditure representing oxygen consumption ↑ UCP1-positive area in BAT ↓ Body weight gain, and weight of EWAT and SWAT	Kamiya et al. [104]
	Isoflavone mixture	Long-Evans male and female rats	600 µg of phytoestrogens/g of diet	↑ Core body temperature during light cycle ↑ Ucp1 in BAT	Lephart et al. [105]
	Daidzein	Male Wistar rats	LFD and HFD with 50 mg/kg for 2 weeks	↑ Ucp1 in BAT in HFD	Crespillo et al. [106]
	Formononetin	Male C57BL/6J mice	HFD with 0.1, 1, and 10 mg of formononetin	↑ SWAT browning ↑ Small and multilocular lipid droplets in SWAT	Gautam et al. [108]

AMPK; 5′ AMP-activated protein kinase, BAT; brown adipose tissue, CPT1α; carnitine palmitoryl transferase 1 alpha, EWAT; epididymal white adipose tissue, HFD; high fat diet, IWAT; Inguinal white adipose tissue, LFD; low fat diet, PPARγ; peroxisome proliferator-activated receptor gamma, PPARα; PPAR alpha, PPARδ; PPAR delta, PGC1α; PPARγ coactivator 1 alpha, PGC1β; PPARγ coactivator 1-beta, RWAT; retroperitoneal white adipose tissue, SD; Sprague Dawley, SIRT1; silent mating type information regulation 2 homolog 1, SWAT; subcutaneous white adipose tissue, TAG; triacylglycerol, UCP1; uncoupling protein 1, ↑; an increase in the experimental group compared to the control group, ↓; a decrease in the experimental group compared to the control group.