Metabolic syndrome is a growing concern in developed societies and due to its polygenic nature, the genetic component is only slowly being elucidated. Common mitochondrial DNA sequence variants have been associated with symptoms of metabolic syndrome and may, therefore, be relevant players in the genetics of metabolic syndrome. We investigate the effect of mitochondrial sequence variation on the metabolic phenotype in conplastic rat strains with identical nuclear but unique mitochondrial genomes, challenged by high-fat diet. We find that the variation in mitochondrial rRNA sequence represents risk factor in the insulin resistance development, which is associated with diacylglycerols accumulation, induced by tissue-specific reduction of the oxidative capacity. These metabolic perturbations stem from the 12S rRNA sequence variation affecting mitochondrial ribosome assembly and translation. Our work demonstrates that physiological variation in mitochondrial rRNA might represent a relevant underlying factor in the progression of metabolic syndrome.

• MeSH
• Diet, High-Fat adverse effects   MeSH
• Genetic Predisposition to Disease MeSH
• Haplotypes * MeSH
• Insulin Resistance genetics   MeSH
• Rats MeSH
• Metabolic Syndrome * genetics   metabolism   MeSH
• DNA, Mitochondrial genetics   metabolism   MeSH
• Mitochondria metabolism   genetics   MeSH
• RNA, Mitochondrial genetics   metabolism   MeSH
• RNA, Ribosomal * genetics   metabolism   MeSH
• Animals MeSH
• Check Tag
• Rats MeSH
• Male MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• DNA, Mitochondrial MeSH
• RNA, Mitochondrial MeSH
• RNA, Ribosomal * MeSH
• RNA, ribosomal, 12S MeSH Browser

To explore the mechanism whereby cGAS-STING pathway regulates the pyroptosis of cryptorchidism cells, with a view to finding a new strategy for clinically treating cryptorchidism-induced infertility. Spermatogonial GC-1 cells were heat stimulated to simulate the heat hurt microenvironment of cryptorchidism. The cell viability was assayed by CCK-8, and cellular DNA damage was detected by gamma-H2AX immunofluo-rescence assay. Flow cytometry was employed to assess pyroptosis index, while western blot, ELISA and PCR were used to examine the expressions of pyroptosis-related proteins (Caspase-1, IL-1beta, NLRP3) and cGAS-STING pathway proteins (cGAS, STING). After STING silencing by siRNA, the expressions of pyroptosis-related proteins were determined. Pyroptosis occurred after heat stimulation of cells. Morphological detection found cell swelling and karyopyknosis. According to the gamma-H2AX immunofluorescence (IFA) assay, the endonuclear green fluorescence was significantly enhanced, the gamma-H2AX content markedly increased, and the endonuclear DNA was damaged. Flow cytometry revealed a significant increase in pyroptosis index. Western blot and PCR assays showed that the expressions of intracellular pyrogenic proteins like Caspase-1, NLRP3 and GSDMD were elevated. The increased STING protein and gene expressions in cGAS-STING pathway suggested that the pathway was intracellularly activated. Silencing STING protein in cGAS-STING pathway led to significantly inhibited pyroptosis. These results indicate that cGAS-STING pathway plays an important role in heat stress-induced pyroptosis of spermatogonial cells. After heat stimulation of spermatogonial GC-1 cells, pyroptosis was induced and cGAS-STING pathway was activated. This study can further enrich and improve the molecular mechanism of cryptorchidism.

• MeSH
• Acetates * MeSH
• Chromogranin A MeSH
• Phenols * MeSH
• Caspase 1 MeSH
• Cryptorchidism * MeSH
• Humans MeSH
• Nucleotidyltransferases MeSH
• NLR Family, Pyrin Domain-Containing 3 Protein MeSH
• Pyroptosis MeSH
• Signal Transduction MeSH
• Spermatogonia MeSH
• Heat Stroke * MeSH
• Check Tag
• Humans MeSH
• Male MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Acetates * MeSH
• Chromogranin A MeSH
• Phenols * MeSH
• GC 1 compound MeSH Browser
• Caspase 1 MeSH
• Nucleotidyltransferases MeSH
• NLR Family, Pyrin Domain-Containing 3 Protein MeSH