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Paradoxical reduction in cardiac O‐GlcNAcylation following short‐term high fat feeding
Author(s) -
Hughey Curtis C,
Zadeh Zarah Ezzat,
Johnsen Virginia L,
Belke Darrell D,
Hittel Dustin S,
Shearer Jane
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.565.15
Subject(s) - oxidative phosphorylation , medicine , endocrinology , phosphorylation , mitochondrion , cardiac function curve , chemistry , biology , biochemistry , heart failure
Chronic high fat feeding (HFF) leads to hyperglycemia which elevates cardiac O‐linked B‐N‐acetylglucosamine glycosylation (O‐GlcNAcylation) of mitochondrial proteins and leads to reduced oxidative phosphorylation. This impairs the hearts ability to oxidize surplus fatty acids perpetuating substrate toxicity associated with lipid excess. We evaluated short‐term HFF on C57BL/6 cardiac O‐GlcNAcylation and mitochondrial function. Following 20 wk HFF, mice were obese (49.12 +/− 0.73 vs. 31.82 +/− 0.95 mg; n=10), but had similar fasting blood glucose (13.98 +/− 1.45 vs. 16.56 +/− 0.91 mM; n=10). High‐resolution respirometry exhibited increased state 3 oxygen consumption supported by complex I substrates in HFF permeabilized cardiac fibers (288.82 +/− 24.81 vs. 188.80 +/− 16.48 pmol/s/mgww; n=8). This was associated with ~1.5‐fold greater mitochondrial density in the HFF group as determined by electron microscopy (n=5). Additionally, global O‐GlcNAcylation decreased ~7‐fold in the HFF mice (n=6) and immunoprecipitation experiments show complex I subunit NDUFA9 O‐GlcNAcylation is reduced ~2.5‐fold (n=6). In conclusion, prior to the onset of hyperglycemia, cardiac mitochondrial oxidative phosphorylation increases to accommodate excess substrate availability due, in part, to enhanced mitochondrial density and decreased O‐GlcNAcylated NDUFA9. This work was supported by CIHR, AHFMR, CDA and HSF.