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Dietary palmitate and palmitate accumulation in the steatotic rat liver confounds fructose‐induced endoplasmic reticulum (ER) stress
Author(s) -
patel chirag r,
Douard Veronique,
Siegel Miles,
Ferraris Ronaldo
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.1106.2
Subject(s) - lipogenesis , steatosis , medicine , endocrinology , unfolded protein response , endoplasmic reticulum , carbohydrate responsive element binding protein , fatty liver , chemistry , fructose , western blot , oxidative stress , biology , biochemistry , lipid metabolism , disease , gene , transcription factor
Consumption of high fructose (HF) results in marked hepatic lipogenesis and steatosis. We recently found dramatic and specific increases in levels of palmitate (P), oleate (O) and other fatty acids in the liver of rats fed HF. P is known to damage hepatocytes via oxidative and ER stress, and to cause dysregulated lipogenesis, conditions that lead to hepatic steatosis. We investigated the contributions of (1) ER stress in F‐induced steatosis, and (2) P in aggravating the adverse effects of F in rats fed isocaloric diets for 3 mo: (glucose (G) + P, G + O, F + P, F + O). Sugars were 40% (w/w), lipids 10%. Dietary F but not G increased fat accumulation in the liver, and dietary P markedly exacerbated this effect. Protein expression of the ER stress and unfolded protein (UPR) response biomarkers binding immunoglobulin protein (BiP) and spliced X‐box binding protein‐1 (XBP‐1s) in whole cell lysate was higher in the liver of rats fed P, independent of dietary sugar. By Western blot, F increased expression of XBP‐1s in nuclear fractions, independent of dietary lipid. By immunocytochemistry, the liver of F‐fed rats had a greater number of nuclei with XBP‐1s. Thus, F induces the inositol‐requiring enzyme 1 (IRE1) pathway of the UPR to ER stress already known to enhance hepatic lipogenesis. P either from the diet or from excessive F intake may aggravate hepatic steatosis. NSF 10S‐1121049