Table 2.

Next-generation mitochondrial uncouplers

Compound	Target tissue	Model	Dose	Body weight	Food intake	Whole-body energy expenditure	FA oxidation	Liver TAGs	Muscle TAGs	Plasma glucose	Plasma insulin	Insulin sensitivity	Plasma lipids	Adverse side effects	References
C12TPP	Systemic	HFD-fed C57BL/6 mice (6 weeks)	50 μM/kg/day × 16 days	↓	↓	↑	↑	ND	ND	ND	ND	ND	ND	None	202
C4R1	Systemic	HFD-fed C57BL/6 mice (8 weeks)	12–14, 30 nM/kg/day × 30 days	↓	↓	↑	↑	ND	ND	ND	ND	ND	ND	Reduction in lean body mass	203
Cl	Systemic	Chow-fed C57BL/6 mice	50 ing/kg × lday	ND	ND	ND	↑	ND	ND	ND	ND	ND	ND	None	204
		db/db mice	50 mg/kg × 4 weeks	-	-	ND	ND	ND	ND	↓	-	↑	-	None
CZ5	Systemic (in vitro uncoupling in muscle and adipose tissue)	Chow-fed C57BL/6 mice	30 mg/kg/day × 30 days	-	↑	↑	↑	ND	ND	-	-	-	ND	None	205
		HFD-fed C57BL/6 mice (8 weeks)	10 mg/kg/day × 5 weeks	↓	↓	↑	ND	-	↓	↓	↓	↑	↓ Cholesterol	None
NEN	Liver	HFD-fed C57BL/6 mice (16 weeks)	150 mg/kg/day × 16 weeks	↓	-	↑	↑	↓	ND	↓	↓	↑	ND	None	206
		db/db mice	150 mg/kg/day × 60 days	-	-	ND	ND	ND	ND	↓	-	ND	ND	None
NPP	Liver	HFD-fed C57BL/6 mice (8 weeks)	125 mg/kg/day × 8 weeks	↓	-	ND	ND	↓	ND	↓	↓	↑	ND	None	207
DNPME	Liver	HFD-fed SD rats (2 weeks)	5 mg/kg/day × 5 days	-	-	-	↑	↓	↓	↓	↓	↑	↓ TAGs	None	51
		T2D rat model	5 mg/kg/day × 14 days	-	-	ND	ND	↓	ND	↓	↓	↑	4. TAGs	None
CRMP	Liver	HFD-fed SD rats (3 weeks)	1 mg/kg/day × 5 days	-	-	-	↑	↓	↓	↓	↓	↑	|TAGs	None	50
		ZDF rats	1 mg/kg/day × 14 days	-	ND	ND	ND	↓	↓	↓	↓	↑	|TAGs	None
		MCD-fed rats (8 weeks)	1 mg/kg/day x× 6 weeks	-	ND	ND	ND	↓	ND	ND	ND	ND	ND	None
		A-ZIP/F-1 mice	2 mg/kg/day × 4 weeks	-	-	-	ND	↓	↓	↓	↓	↑	|TAGs	None	60