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RGS/G‐Protein Control of Liver Carbohydrate and Fatty Acid Metabolism
Author(s) -
Wilkie Thomas Martin,
Huang Jie,
Pashkov Victor
Publication year - 2006
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.20.4.a256
Subject(s) - medicine , endocrinology , biology , fatty liver , knockout mouse , transgene , beta oxidation , steatosis , glycogen , receptor , metabolism , biochemistry , gene , disease
G protein coupled receptor (GPCR) pathways directly and indirectly control metabolic rate and feeding behaviors that influence the onset of obesity and metabolic syndrome. Regulators of G protein Signaling (RGS) proteins are negative regulators that control the intensity and duration of G protein signaling. One RGS gene, Rgs16 , is dynamically regulated in liver by feeding and fasting. Monosaccharides induce Rgs16 transcription, and mRNA and protein stability both in vivo and in cultured liver slices, whereas feeding rapidly down regulates transcription. Transgenic mice that express Rgs16 protein specifically in liver have hepatic steatosis and lower glycogen storage compared to wild type controls. In addition, fasted Rgs16 transgenic mice have reduced expression of genes promoting fatty acid oxidation, and lower β‐ketone levels in blood. Similar phenotypes were observed in Gα11−/− knockout mice. Fatty liver is considered to be a hepatic manifestation of metabolic syndrome. We propose Rgs16 is a glucose‐responsive inhibitor of Gq/11‐stimulated fatty acid oxidation in liver. Research supported by the NIH & Welch Foundation.