Mouse HFD Liver Skeletal Muscle SLC16A13 Knock-Out
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. Overall design: We profiled liver and skeletal muscle bulk tissue from 11 SCL16A13 knock-out vs. 11 wild type mice