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Mouse HFD Liver Skeletal Muscle SLC16A13 Knock-Out

ABSTRACT: Genome-wide association identified SLC16A13 as novel type 2 diabetes gene locus. The SLC16A13 gene encodes for SLC16A13/MCT13, member of the solute carrier 16 family of monocarboxylate transporters. This transporter family recently raised interest in metabolic research with the identification of SLC16A11 polymorphisms associated with type 2 diabetes; and human as well as mouse data suggest causal relationship between SLC16A11/MCT11 transporter dysfunction and type 2 diabetes development. In contrast, SLC16A13 biology and physiological function is not characterized at all. Here, we validate SLC16A13 as monocarboxylate transporter expressed at the plasma membrane and report the first Slc16a13 knockout mouse line. Deletion of Slc16a13 ameliorates metabolic disease in the context of diet-induced obesity. The improved metabolic phenotype is characterized by increased mitochondrial respiration in the liver, leading to reduced hepatic lipid accumulation and increased insulin sensitivity of Slc16a13 knockout mice. Mechanistically, we propose reduced intracellular lactate availability in Slc16a13 knockout hepatocytes, affecting hepatic energy metabolism by AMPK activation and increased oxidative phosphorylation, reducing hepatic lipid content and insulin resistance in obese mice. Together, these data suggest SLC16A13/MCT13 as potential novel target to treat fatty liver, insulin resistance and related metabolic disorders.

ORGANISM(S): Mus musculus

PROVIDER: GSE152937 | GEO | 2021/06/24

REPOSITORIES: GEO

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