title: Dipeptidyl peptidase 9 enzymatic activity influences the expression of neonatal metabolic genes.
abstract: The success of dipeptidyl peptidase 4 (DPP4) inhibition as a type 2 diabetes therapy has encouraged deeper examination of the post-proline DPP enzymes. DPP9 has been implicated in immunoregulation, disease pathogenesis and metabolism. The DPP9 enzyme-inactive (Dpp9 gene knock-in; Dpp9 gki) mouse displays neonatal lethality, suggesting that DPP9 enzyme activity is essential in neonatal development. Here we present gene expression patterns in these Dpp9 gki neonatal mice. Taqman PCR arrays and sequential qPCR assays on neonatal liver and gut revealed differential expression of genes involved in cell growth, innate immunity and metabolic pathways including long-chain-fatty-acid uptake and esterification, long-chain fatty acyl-CoA binding, trafficking and transport into mitochondria, lipoprotein metabolism, adipokine transport and gluconeogenesis in the Dpp9 gki mice compared to wild type. In a liver cell line, Dpp9 knockdown increased AMP-activated protein kinase phosphorylation, which suggests a potential mechanism. DPP9 protein levels in liver cells were altered by treatment with EGF, HGF, insulin or palmitate, suggesting potential natural DPP9 regulators. These gene expression analyses of a mouse strain deficient in DPP9 enzyme activity show, for the first time, that DPP9 enzyme activity regulates metabolic pathways in neonatal liver and gut.
authors.affiliation: Centenary Institute and Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia.
authors.forename: Yiqian
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Centenary Institute and Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia.
authors.forename: Margaret G
authors.initials: MG
authors.lastname: Gall
authors.affiliation: Centenary Institute and Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia.
authors.forename: Hui
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Centenary Institute and Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia.
authors.forename: Fiona M
authors.initials: FM
authors.lastname: Keane
authors.affiliation: Centenary Institute and Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia.
authors.forename: Geoffrey W
authors.initials: GW
authors.lastname: McCaughan
authors.affiliation: Centenary Institute and Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia.
authors.forename: Denise M T
authors.initials: DM
authors.lastname: Yu
authors.affiliation: Centenary Institute and Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia. Electronic address: m.gorrell@centenary.usyd.edu.au.
authors.forename: Mark D
authors.initials: MD
authors.lastname: Gorrell
mesh_terms: D000263:Adenylate Kinase / Q000378:metabolism; D054392:Adipokines / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D002460:Cell Line; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases / Q000235:genetics / Q000378:metabolism*; D004789:Enzyme Activation; D004815:Epidermal Growth Factor / Q000502:physiology; D015870:Gene Expression; D018507:Gene Expression Regulation, Developmental; D017228:Hepatocyte Growth Factor / Q000502:physiology; D006801:Humans; D007328:Insulin / Q000502:physiology; D050356:Lipid Metabolism; D008099:Liver / Q000201:enzymology; D008822:Mice, Transgenic; D019308:Palmitic Acid / Q000494:pharmacology
chemical_list: D054392:Adipokines; C066855:HGF protein, human; D007328:Insulin; D019308:Palmitic Acid; D004815:Epidermal Growth Factor; D017228:Hepatocyte Growth Factor; D000263:Adenylate Kinase; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases; C585326:dipeptidyl peptidase 9, mouse
keywords: AMPK; DPP9; Dipeptidyl peptidase; Neonatal metabolism