TABLE 1.

Transgenic models of lipotoxicity

Model	Comments
Cardiomyocyte overexpression of PPAR-α	Mice develop a lipotoxic cardiomyopathy that is associated with increased FAO, decreased glucose oxidation, and increased peroxisomal production of ROS (102). Phenotype is worsened by diets high in saturated fat, improved by diets enriched in medium-chain FAs (101), and reversed when CD36 is knocked out (382).
Cardiomyocyte expression of membrane-anchored LPL	Mice develop lipotoxic cardiomyopathy (381). Overexpression of apolipoprotein B in hearts reverses lipid overload and restores heart function (386). PPAR-γ but not PPAR-α agonists also reduce lipotoxicity and restore heart function (363). Most of the lipid that contributes to lipotoxicity in this model is derived from triglyceride-containing lipoprotein particles (280).
Cardiomyocyte overexpression of acyl CoA synthase	These mice develop lipotoxic cardiomyopathy, lipoapoptosis, and systolic dysfunction (51). Increasing leptin levels via adenoviral overexpression in livers reverses the lipotoxicity and restores cardiac function (202). α-Lipoic acid also reverses lipotoxic cardiomyopathy (203).
Cardiomyocyte overexpression of FATP	These mice develop lipotoxicity, increased FAO, decreased glucose oxidation but develop diastolic dysfunction with relatively preserved systolic function. Free FAs but not triglycerides are increased in these hearts (50).
Cardiomyocyte-restricted KO of PPAR-δ	Animals develop cardiac lipotoxicity and heart failure on the basis of a reduction in mitochondrial FAO (47).
Adipose tissue triglyceride lipase KO mice	Develop massive cardiac lipid accumulation because of inability to break down triglycerides (127).

PPAR, peroxisome proliferator-activated receptor; KO, knockout; FAO, fatty acid oxidation; ROS, reactive oxygen species; FA, fatty acid.