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Fatty acid‐mediated endoplasmic reticulum stress in the liver in vivo: Differential response to saturated and unsaturated fatty acids
Author(s) -
Nivala Angela,
Reese Lauren,
Hemenway Erica,
Gentile Christopher,
Pagliassotti Michael
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.145.13
Subject(s) - in vivo , endoplasmic reticulum , chemistry , adipose tissue , fatty acid , fatty liver , medicine , endocrinology , biochemistry , biology , microbiology and biotechnology , disease
In cell systems, saturated fatty acids are generally more cytotoxic than unsaturated fatty acids. In the present study we examined hepatic cytotoxicity in response to unsaturated and saturated fats in vivo. Lipid emulsions containing glycerol, phosphatidylcholine, penicillin (CON, n=6) and either soybean oil (UNSAT, n=7) or lard oil (SAT, n=7) were infused intravenously into rats over a 4 hour period under conditions in which glucose and insulin levels were held constant. Free fatty acids levels were 0.5 ± 0.1 mM (mean ± SD) in CON and were increased to 1.7 ± 0.3 mM and 1.6 ± 0.3 mM in UNSAT and SAT, respectively. Glucose and insulin levels were not different among groups. Markers of endoplasmic reticulum (ER) stress and activation of inflammatory pathway signaling were increased in livers from SAT and UNSAT compared to CON, but were increased to a greater extent in SAT compared to UNSAT. Several genes linked to inflammation were significantly increased in adipose tissue of UNSAT and SAT compared to CON, but were increased to a greater extent in SAT compared to UNSAT. These data suggest that elevated free fatty acids can induce hepatic ER stress in vivo. In addition, SAT fatty acids appear to be more cytotoxic than UNSAT fatty acids in vivo.