Table 1.

Future Potential Therapeutic Strategies to Treat Obesity by Targeting Mitochondria in White Adipocytes

Strategies	Therapeutic target area or putative drugs	Advantages	Disadvantages	References
To increase energy expenditure in white adipocytes	OXPHOS uncoupling molecules (ie, FCCP, DNP, constitutive over-expression of UCP1)	Triglyceride content decreased	Insulin sensitivity impaired	21, 91
			Lipolysis increased	92, 94
		Metabolic rate increased	Fatty acid release increased
To induce a reduction of white adipocyte number	Apoptosis inducers (ie, FAT-ATTAC mouse, Ajoene)	Abundance of adipose tissue reduced	Abnormal fat accumulation (ie, muscle, liver)	108, 110
			Glucose intolerance
			Insulin secretion decreased
			Circulating adipokines level decreased
To induce white adipocyte transdifferentiation into brown-like adipocytes	Ectopic expression of PGC-1α	Lipid oxidation increased	Not known	112,113,114,115
	Overexpression of leptin
	Treatment with trans-retinoic acid	Lipogenic enzymes down-regulated
		Body fat decreased
To increase mitochondrial oxidative capacity	Bioactive food components (ie, polyunsaturated fatty acid, polyphenols such as resveratrol)	Lipid oxidation increased	Not known	117,118,119,120
				122,123,124,125,126,127
		Body fat decreased
		Mitochondrial biogenesis increased
	Synthetic mimetic directed at SIRT1 activation (ie, SRT-1720, SRT-501)
		Lifespan increased
		Insulin sensitivity improved