at age of 30 week indicated their maximum of weight gain with a mean weight of 40 g. Food intake of C57Bl6 and alb-SREBP-1a mice was not different whereas alb-SREBP-1aDP mice consumed approximately 20% less. At 24 weeks body weight of alb-SREBP1aDP mice was like C57Bl6 wereas alb-SREBP-1a were significantly higher. This was also observed for liver weight and white adipose tissue. The ammount of white adipose tissue per body weight was nearly doubled in albSREBP-1a whereas again alb-SREBP-1aDP and C57 were identical. In relation to body weight food uptake was comparable in both models and controls. In contrast, weight gain per food intake disclosed that the amount of food consumed by alb-SREBP-1aDP was significantly SB-705498 cost higher than C57Bl6. More impressively this was calculated for alb-SREBP-1a mice. Taken together, preventing phophorylation of the overexpressed transgene SREBP-1a by mutation of the Systemic influence of SREBP-1a phosphorylation Phosphorylation of SREBP-1a by JNK and p38 Kinases 9 Phosphorylation of SREBP-1a by JNK and p38 Kinases 1a mice have a circa threefold higher value as C57Bl6. According to this only the alb-SREBP-1a mice had significantly elevated liver function tests, i.e. GPT/ALT and GOT/AST, respectively. Leptin levels were elevated only in alb-SREBP-1a mice in accordance to the increased fat mass. Blood glucose and insulin were increased in alb-SREBP-1a mice, whereas in alb-SREBP-1aDP mice soley insulin was modestly elevated. As expected the content of total fatty acid in liver of albSREBP-1a mice was approximately fourfold higher as in liver of C57Bl6 mice. In contrast the phosphorylation deficient mice were mostly protected against lipid accumulation and show a 1.5 foldincrease. Detailed analyses of fatty acid composition in liver tissues and serum were performed. In liver the content of saturated FA, i.e. C16:0 was unaltered and C18:0 was slightly reduced in phosphorylation deficient mice alb-SREBP-1aDP but massively reduced alb-SREBP1a mice in comparison to C57Bl6. The level of mono unsaturated FA C16:1 was increased three fold in alb-SREBP-1aDP and four fold alb-SREBP-1a mice. C18:1 showed an 1.5 fold- increase in alb-SREBP-1aDP and a 2.5 foldincrease alb-SREBP-1a mice. Polyunsaturated fatty acids PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/22187127 C18:2, C18:3 and C20:4 contend showed a genotypespecific reduction in the transgenic mouse models which was most prominent in albSREBP-1a mice whereas alb-SREBP-1aDP mice were more comparable to C57Bl6. Compared to the levels determined for C57Bl6, there is a pronounced increase in C16:1 and C18:1 for alb-SREBP-1aDP that is further 
doubled in alb-SREBP-1a mice. Also the reduced levels for the further FA observed in alb-SREBP1aDP were nearly doubled in alb-SREBP-1a mice. In serum the FFA pattern of mice is essentially comparable to liver, but the differences are not that pronounced. Also the differences in relation to C57Bl6 when significant, again show a pattern with the largest differences observed for alb-SREBP-1a mice and the albSREBP-1aDP beeing intermediate to C57BL6 and alb-SREBP-1a mice. Phosphorylation of SREBP-1a influences insulin sensitivity The mice overexpressing functional SREBP-1a in liver developed a fatty liver, but the phenotype is abrogated if the main phosphorylation sites in SREBP-1a were mutated as in albSREBP-1aDP mice. Excess intracellular lipid accumulation in hepatocytes impairs liver functionality and insulin sensitivity. Caculating of HOMA-IR index as surogate for insulin resistance indic
