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Characterization and Proteomic-Transcriptomic Investigation of Monocarboxylate Transporter 6 Knockout Mice: Evidence of a Potential Role in Glucose and Lipid Metabolism.
Jones RS, Tu C, Zhang M, Qu J, Morris ME.
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Monocarboxylate transporter 6 [(MCT6), SLC16A5] is an orphan transporter with no known endogenous substrates or physiological role. Previous in vitro and in vivo experiments investigated MCT6 substrate/inhibitor specificity in Xenopus laevis oocytes; however, these data remain limited. Transcriptomic changes in the livers of mice undergoing different dieting schemes have suggested that Mct6 plays a role in glucose and lipid metabolism. The objectives of this study were 1) to develop a novel knockout (KO) mouse model (Mct6-/-) using CRISPR/Cas9 technology, 2) to characterize the KO animal model by examining physiological and biochemical parameters, and 3) to understand the physiological role of MCT6 in vivo through global proteomic and liver transcriptomic profiling. mRNA tissue analysis demonstrated knockout of Mct6, which showed greater than 90% knockdown of Mct6 (Slc16a5) gene expression in all major tissues analyzed when normalized to Mct6+/+ mice. Proteomic analyses identified greater than 4000 unique proteins in kidney, liver, and colon tissues, among which 51, 38, and 241 proteins were significantly altered, respectively (for each tissue), between Mct6+/+ and Mct6-/- mice. Additionally, Mct6-/- mice demonstrated significant changes in 199 genes in the liver compared with Mct6+/+ mice. In silico biological pathway analyses revealed significant changes in proteins and genes involved in glucose and lipid metabolism-associated pathways. This study is the first to provide evidence for an association of Mct6 in the regulation of glucose and lipid metabolism. SIGNIFICANCE STATEMENT: This paper focuses on elucidating the innate biological role of an orphan transporter in vivo, which has not been investigated thus far. Using efficient and high-throughput technologies, such as CRISPR/Cas9 gene editing, liquid chromatography-tandem mass spectrometry-based proteomic and RNA-sequencing transcriptomic analyses, our laboratory provides the first existence and characterization of a Mct6 knockout mouse model. The evidence gathered in this paper, as well as other laboratories, support the importance of MCT6 in regulating a variety of glucose and lipid metabolic pathways, which may indicate its significance in metabolic diseases.
Abe,
Monocarboxylate transporter 10 functions as a thyroid hormone transporter in chondrocytes.
2012, Pubmed
Abe,
Monocarboxylate transporter 10 functions as a thyroid hormone transporter in chondrocytes.
2012,
Pubmed Allen-Jennings,
The roles of ATF3 in liver dysfunction and the regulation of phosphoenolpyruvate carboxykinase gene expression.
2002,
Pubmed An,
Surfactant-aided precipitation/on-pellet-digestion (SOD) procedure provides robust and rapid sample preparation for reproducible, accurate and sensitive LC/MS quantification of therapeutic protein in plasma and tissues.
2015,
Pubmed Anders,
HTSeq--a Python framework to work with high-throughput sequencing data.
2015,
Pubmed Castorino,
Juvenile cataract-associated mutation of solute carrier SLC16A12 impairs trafficking of the protein to the plasma membrane.
2011,
Pubmed de Pablo,
Modulatory effects of dietary lipids on immune system functions.
2000,
Pubmed Dhayat,
Mutation in the Monocarboxylate Transporter 12 Gene Affects Guanidinoacetate Excretion but Does Not Cause Glucosuria.
2016,
Pubmed
,
Xenbase Dumitrescu,
Tissue-specific thyroid hormone deprivation and excess in monocarboxylate transporter (mct) 8-deficient mice.
2006,
Pubmed Dunn,
Procedures for large-scale metabolic profiling of serum and plasma using gas chromatography and liquid chromatography coupled to mass spectrometry.
2011,
Pubmed Foks,
Interference of the CD30-CD30L pathway reduces atherosclerosis development.
2012,
Pubmed Friesema,
Identification of monocarboxylate transporter 8 as a specific thyroid hormone transporter.
2003,
Pubmed
,
Xenbase Getz,
The mutual interplay of lipid metabolism and the cells of the immune system in relation to atherosclerosis.
2014,
Pubmed Gill,
Expression and membrane localization of MCT isoforms along the length of the human intestine.
2005,
Pubmed Halestrap,
The SLC16 gene family-from monocarboxylate transporters (MCTs) to aromatic amino acid transporters and beyond.
2004,
Pubmed Harayama,
Understanding the diversity of membrane lipid composition.
2018,
Pubmed Harris,
Prostaglandins as modulators of immunity.
2002,
Pubmed Huang,
Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources.
2009,
Pubmed Huang,
Bioinformatics enrichment tools: paths toward the comprehensive functional analysis of large gene lists.
2009,
Pubmed Iwanaga,
Cellular expression of monocarboxylate transporters (MCT) in the digestive tract of the mouse, rat, and humans, with special reference to slc5a8.
2006,
Pubmed Jones,
Quercetin, Morin, Luteolin, and Phloretin Are Dietary Flavonoid Inhibitors of Monocarboxylate Transporter 6.
2017,
Pubmed
,
Xenbase Jones,
Monocarboxylate Transporters: Therapeutic Targets and Prognostic Factors in Disease.
2016,
Pubmed Kirat,
Monocarboxylate transporter 1 (MCT1) mediates transport of short-chain fatty acids in bovine caecum.
2006,
Pubmed Kirat,
Monocarboxylate transporter 1 (MCT1) plays a direct role in short-chain fatty acids absorption in caprine rumen.
2006,
Pubmed Kirat,
Regional and cellular distribution of monocarboxylate transporters 13 and 14 in the cattle gastrointestinal tract.
2015,
Pubmed Kirat,
Expression, cellular localization, and functional role of monocarboxylate transporter 4 (MCT4) in the gastrointestinal tract of ruminants.
2007,
Pubmed Kirat,
Monocarboxylate transporter 1 gene expression in the ovine gastrointestinal tract.
2006,
Pubmed Kohyama,
Characterization of monocarboxylate transporter 6: expression in human intestine and transport of the antidiabetic drug nateglinide.
2013,
Pubmed
,
Xenbase Livak,
Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method.
2001,
Pubmed Love,
Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2.
2014,
Pubmed Lu,
Metabolic crosstalk: molecular links between glycogen and lipid metabolism in obesity.
2014,
Pubmed Lu,
Comparative transcriptomic and metabolomic analysis of fenofibrate and fish oil treatments in mice.
2011,
Pubmed Luan,
Food Fight: Role of Itaconate and Other Metabolites in Antimicrobial Defense.
2016,
Pubmed Ma,
Comparative Proteomic Analysis of the Mitochondria-associated ER Membrane (MAM) in a Long-term Type 2 Diabetic Rodent Model.
2017,
Pubmed Murakami,
Functional characterization of human monocarboxylate transporter 6 (SLC16A5).
2005,
Pubmed
,
Xenbase Ran,
Genome engineering using the CRISPR-Cas9 system.
2013,
Pubmed Ricciotti,
Prostaglandins and inflammation.
2011,
Pubmed Rubio-Aliaga,
Targeted disruption of the peptide transporter Pept2 gene in mice defines its physiological role in the kidney.
2003,
Pubmed Rusu,
Type 2 Diabetes Variants Disrupt Function of SLC16A11 through Two Distinct Mechanisms.
2017,
Pubmed Safe,
Nuclear receptor 4A (NR4A) family - orphans no more.
2016,
Pubmed Schwartz,
Allan-Herndon-Dudley syndrome and the monocarboxylate transporter 8 (MCT8) gene.
2005,
Pubmed Shen,
IonStar enables high-precision, low-missing-data proteomics quantification in large biological cohorts.
2018,
Pubmed Singal,
Antioxidants as therapeutic agents for liver disease.
2011,
Pubmed Trapnell,
TopHat: discovering splice junctions with RNA-Seq.
2009,
Pubmed van Acker,
Flavonoids can replace alpha-tocopherol as an antioxidant.
2000,
Pubmed Wang,
RSeQC: quality control of RNA-seq experiments.
2012,
Pubmed Wang,
Temporal Effects of Combined Birinapant and Paclitaxel on Pancreatic Cancer Cells Investigated via Large-Scale, Ion-Current-Based Quantitative Proteomics (IonStar).
2018,
Pubmed Welter,
Expression of the monocarboxylate transporter 1 (MCT1) in cells of the porcine intestine.
2008,
Pubmed Wojczynski,
Genome-wide association study of triglyceride response to a high-fat meal among participants of the NHLBI Genetics of Lipid Lowering Drugs and Diet Network (GOLDN).
2015,
Pubmed Wu,
Regulation of T cell signalling by membrane lipids.
2018,
Pubmed Wu,
Activation of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase during high fat diet feeding.
2013,
Pubmed Xu,
Impairment of Intestinal Monocarboxylate Transporter 6 Function and Expression in Diabetic Rats Induced by Combination of High-Fat Diet and Low Dose of Streptozocin: Involvement of Butyrate-Peroxisome Proliferator-Activated Receptor-γ Activation.
2019,
Pubmed Yen,
Intestinal triacylglycerol synthesis in fat absorption and systemic energy metabolism.
2015,
Pubmed Yoshimatsu,
Induction of macrophage scavenger receptor MARCO in nonalcoholic steatohepatitis indicates possible involvement of endotoxin in its pathogenic process.
2004,
Pubmed Zhang,
Gene expression profile change and associated physiological and pathological effects in mouse liver induced by fasting and refeeding.
2011,
Pubmed
