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Adv Exp Med Biol. 2017;960:197-220. doi: 10.1007/978-3-319-48382-5_8.

What Is Lipotoxicity?

Author information

1
Faculty of Pharmacy, Department of Toxicology, Gazi University, Hipodrom, Ankara, Turkey. abengin@gmail.com.

Abstract

Enlarged fat cells in obese adipose tissue diminish capacity to store fat and are resistant to the anti-lipolytic effect of insulin. Insulin resistance (IR)-associated S-nitrosylation of insulin-signaling proteins increases in obesity. In accordance with the inhibition of insulin-mediated anti-lipolytic action, plasma free fatty acid (FFA) levels increase. Additionally, endoplasmic reticulum stress stimuli induce lipolysis by activating cyclic adenosine monophosphate/Protein kinase A (cAMP/PKA) and extracellular signal-regulated kinase ½ (ERK1/2) signaling in adipocytes. Failure of packaging of excess lipid into lipid droplets causes chronic elevation of circulating fatty acids, which can reach to toxic levels within non-adipose tissues. Deleterious effects of lipid accumulation in non-adipose tissues are known as lipotoxicity. In fact, triglycerides may also serve a storage function for long-chain non-esterified fatty acids and their products such as ceramides and diacylglycerols (DAGs). Thus, excess DAG, ceramide and saturated fatty acids in obesity can induce chronic inflammation and have harmful effect on multiple organs and systems. In this context, chronic adipose tissue inflammation, mitochondrial dysfunction and IR have been discussed within the scope of lipotoxicity.

KEYWORDS:

Ceramide; Diacylglycerol (DAG); Fatty acid translocase (FAT)/CD36; Fatty acyl-coenzyme A (FA-CoA); Free fatty acid (FFA); Insulin resistance (IR); Lipid droplets; Lipolysis; Lipotoxicity; Long-chain fatty acid (LCFA); Mitochondrial dysfunction; Obesity; Perilipin; Plasma membrane-associated fatty acid binding protein (FABPpm); Reactive oxygen species (ROS); Triacylglycerol; Triglyceride

PMID:
28585200
DOI:
10.1007/978-3-319-48382-5_8
[Indexed for MEDLINE]

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