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Insulin and Docosahexaenoic Acid (22:6,n‐3) Regulate Rat Hepatocyte Sterol Regulatory Element Binding Protein‐1 (SREBP‐1) Nuclear Abundance
Ist Teil von
The FASEB journal, 2006-03, Vol.20 (5), p.A958-A959
Ort / Verlag
Federation of American Societies for Experimental Biology
Erscheinungsjahr
2006
Link zum Volltext
Quelle
Alma/SFX Local Collection
Beschreibungen/Notizen
Insulin induces and n‐3 polyunsaturated fatty acids (PUFA) suppress hepatic de novo lipogenesis by controlling SREBP‐1 nuclear abundance (nSREBP‐1). Insulin induction of nSREBP‐1 is preceded by rapid, but transient, increases in Akt, Erk and Gsk3beta phosphorylation. Removal of insulin from hepatocytes promotes a decline in nSREBP‐1 (T1/2 ~ 10 hrs) that is abrogated by 26S‐proteasome inhibitors. 22:6,n‐3 accumulates in livers of fish‐oil fed rats and suppresses hepatic nSREBP‐1. 22:6 suppression of nSREBP‐1 cannot be accounted for by changes in SCAP, Insig‐1 or ‐2 expression. Instead, 22:6 accelerates the loss of nSREBP‐1 (T1/2~ 4 hrs) with minimal effects on microsomal SREBP‐1 or nuclear SREBP‐2. 26S proteasome inhibitors attenuate 22:6 suppression of nSREBP‐1. 22:6 transiently inhibits insulin‐induced Akt phosphorylation, but induces both Erk and Gsk3beta phosphorylation. MEK inhibitors of Erk phosphorylation, but not overexpressed constitutively active Akt, attenuate 22:6 suppression of nSREBP‐1. In conclusion, 22:6,n‐3 suppresses hepatocyte nSREBP‐1 through 26S proteasome‐ and MEK/Erk‐dependent pathways. Phospho‐Gsk3beta is inactive and may not be involved in 22:6,n‐3 regulation of nSREBP‐1.
Supported by NIH DK43220, USDA 2003‐5200‐3400 and MAES.