Table 2. The chemical structures of some novel PPARα/γ dual agonists which are under preclinical stages and their key pharmacological effects.

PPARα/γ Dual Agonist	Chemical Structure	Key Effects/Advantages
LT175		In mice fed a high-fat diet, the LT175 administration has decreased body weight, adipocyte size and the white adipose tissue mass, and it also significantly reduced the plasma glucose, insulin, non-esterified fatty acids, triglycerides and cholesterol [34].
CG301269		CG301269 has a potential to selectively stimulate the transcriptional activities of PPARα and PPARγ. Interestingly, CG301269 was noted to reduce the inflammatory responses and fatty liver without inducing the body weight gain in db/db mice. Moreover, CG301269 was noted to ameliorate insulin resistance and hyperlipidemia in vivo [35].
Amodiaquine		Amodiaquine has a potential to selectively activate PPARα/γ transcriptional activities. Intriguingly, in high fat diet-induced obese and genetically modified obese-diabetic mice, amodiaquine was noted to remarkably ameliorate insulin resistance, hyperlipidemia and fatty liver, and also to decrease the body weight gain [36].
Propane-2-sulfonic acid octadec-9-enyl-amide (N15)		The compound, N15 has advantageous effects on glucose and lipid metabolism without triggering the weight gain in mice. Its glucose-lowering effect has been suggested to be associated with PPARγ-mediated upregulation of hepatic glucose consumption and downregulation of gluconeogenesis [37].
SN158		The compound, SN158 has been shown to interact with PPARα and PPARγ and to increase the transcriptional activities of both. Interestingly, SN158 has been noted to significantly lower the plasma glucose, triglycerides, and free fatty acids in ob/ob mice without having severe weight gain and hepatomegaly [38].
MHY908		Supplementation with MHY908 showed reduced serum glucose and triglyceride levels, and also reduced liver triglyceride levels in aged rats [40].
Amorphastilbol		Amorphastilbol has been shown to selectively stimulate the transcriptional activities of PPARα and PPARγ. It improved glucose and lipid impairment in db/db mice. Moreover, there were no significant adverse effects like weight gain or hepatomegaly noted in amorphastilbol-treated animals [41].