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Currently available models insufficiently reflect the pathogenic alternation of nonalcoholic steatohepatitis\NASH), such as insulin resistance. The present study aimed to characterize a novel NASH model caused by feeding the diet containing conjugated linoleic acid (CLA). In this study, mice were fed a control diet or the diet containing 0.5% CLA for 8 weeks. The insulin tolerance test (ITT) and homeostasis model assessment of insulin resistance (HOMA-IR) were used to determine the extent of insulin resistance. Liver lipotoxicity and inflammation were assessed by endoplasmic reticulum (ER) stress, autolipophagy, recruitment of Kupffer cells and hepatic stellate cell (HSC) activation. We found that liver weight was markedly increased, and histopathological examination showed marked macrosteatosis with focal hepatocellular death through apoptosis, and mild pericellular fibrosis with Kupffer cell recruitment and HSC activation, as well as light chain IIIβ-positive cells and enhanced ER stress in mice fed the CLA-containing diet. Enhanced synthesis and reduced β-oxidation of fatty acids resulted in their accumulation and lipotoxicity in hepatocytes. A biophotonic technology revealed lipid droplet accumulation in the liver from mice fed the CLA-containing diet, and Raman spectroscopic analysis indicated that these lipid droplets predominantly contained saturated fatty acids. Elevated fasting insulin levels, abnormal ITT and HOMA-IR confirmed the marked insulin resistance in these mice. Decreased phosphorylation of the insulin-signaling molecule Akt was partially responsible for the significant insulin resistance. In conclusion, Mice fed the diet containing CLA-developed steatohepatitis with marked insulin resistance, which is similar to the characteristics observed in NASH patients. The further characterization of this model would be particularly useful for revealing the critical role of insulin resistance in NASH development in conditions such as metabolic syndrome, diabetes and obesity.

The suborder Corynebacterianeae comprises bacteria like Mycobacterium tuberculosis and Corynebacterium glutamicum , and these bacteria contain in addition to the linear fatty acids, unique α-branched β-hydroxy fatty acids, called mycolic acids. Whereas acetyl-coenzyme A (CoA) carboxylase activity is required to provide malonyl-CoA for fatty acid synthesis, a new type of carboxylase is apparently additionally present in these bacteria. It activates the α-carbon of a linear fatty acid by carboxylation, thus enabling its decarboxylative condensation with a second fatty acid to afford mycolic acid synthesis. We now show that the acetyl-CoA carboxylase of C. glutamicum consists of the biotinylated α-subunit AccBC, the β-subunit AccD1, and the small peptide AccE of 8.9 kDa, forming an active complex of approximately 812,000 Da. The carboxylase involved in mycolic acid synthesis is made up of the two highly similar β-subunits AccD2 and AccD3 and of AccBC and AccE, the latter two identical to the subunits of the acetyl-CoA carboxylase complex. Since AccD2 and AccD3 orthologues are present in all Corynebacterianeae , these polypeptides are vital for mycolic acid synthesis forming the unique hydrophobic outer layer of these bacteria, and we speculate that the two β-subunits present serve to lend specificity to this unique large multienzyme complex.