 During obesity or periods of overnutrition, lipid accumulates in nonadipose tissues, notably skeletal muscle, liver, heart, and pancreas due to cellular uptake of exogenous fatty acids, triglycerides, and cholesterol as well as de novo lipogenesis in response to elevated glucose. The accumulation of intracellular lipid leads to high levels of free fatty acids that are subject to oxidative damage and the formation of cytotoxic and highly reactive lipid peroxides, which ultimately are detrimental to intracellular organelles, particularly the endoplasmic reticulum ER and mitochondria. Exposure of the ER to high levels of free fatty acids and lipid peroxides causes structural alterations that perturb ER function and lead to accumulation of unfolded proteins and calcium release. Failure of the UPR to reestablish ER homeostasis can lead to apoptosis .When mitochondria are exposed to high levels of free fatty acids, these can become oxidized by mitochondrial reactive oxygen species, forming lipid peroxides that damage essential proteins and uncouple mitochondrial function. This results in mitochondrial damage, which can cause further accumulation of lipids that cannot be catabolized, disrupted cellular homeostasis, and ultimately apoptosis . 