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IRS‐1/2 Mediated Regulation of Hepatic OGT and OGA Expression
Author(s) -
Sundararaj Kamala,
Alqalam Abdelmohsen M,
Robinson Katherine A,
Buse Maria G,
Ball Lauren E
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.759.15
Subject(s) - postprandial , medicine , endocrinology , adipose tissue , insulin , gene expression , chemistry , biology , gene , biochemistry
To investigate the role of hepatic insulin signaling in the postprandial regulation of O‐GlcNAc transferase (OGT) and OGlcNAcase (OGA) expression, C57BL/6 male mice with a conditional knock out of IRS‐1/2 in liver (LKO) were fed a chow or high fat diet (HFD) for 16 weeks and then either fasted for 18hrs or fasted and refed ad libitum for 4hrs. In control animals that were fasted or refed, qRT‐PCR revealed a postprandial increase in hepatic OGT expression (146% ± 12.8, n=5) and a reduction in OGA transcript levels (65.7% ± 6.1, n=5). The postprandial increase in hepatic OGT expression was attenuated in LKO mice. In control mice, high fat feeding attenuated both the postprandial rise in hepatic OGT expression (123% ± 5.0, n=5) and the suppression of OGA expression (77.2% ± 4.6, n=5). In LKO mice in the refed state, OGT mRNA expression was reduced by 68% ± 1.5 (n=5) after 16 weeks HFD as compared to animals fed a chow diet. Furthermore with 16 weeks HFD, elevated expression of OGA was observed in hepatic (170% ± 7.5) and adipose (316.5% ± 21.6, n=5) tissue as compared to chow diet. These studies reveal that the postprandial changes in hepatic expression of OGA and OGT are regulated, in part, by IRS‐1/2 mediated insulin signaling in vivo and that the suppression of OGA expression in fat fed animals is lost in the absence of hepatic IRS‐1/2. Supported by T32 HL07260 and RO1DK002001.