Born to run; the story of the PEPCK-Cmus mouse
It has some surprising implications, and ties in with my previous post. This study would seem to suggest that it is NOT calorie restriction that promotes longevity, but rather it is having a high number of mitochondria and running your metabolism on fat!
These studies focused mainly on the potential role of PEPCK-C in the generation of alanine, which occurs during fasting in skeletal muscleAlanine is the main amino acid ejected from muscle during fasting to fuel for glucose creation to support the brain.
biochemical analysis of the skeletal muscle indicated high levels of triglyceride in that tissue. In fact, the concentration of triglyceride in the skeletal muscle of the PEPCK-Cmus mice was directly proportional to the activity of PEPCK-C in the muscle, suggesting the importance of glyceroneogenesis in the tissue.Fat burning metabolism folks.
Skeletal muscle triglyceride is clearly the major fuel driving the hyperactivity in the PEPCK-Cmus mice; they have many more mitochondria in their skeletal muscle than found in the muscle of controls, supporting the enhanced rates of fatty acid metabolism noted in the mice.What did I just say?
After weaning, the PEPCK-Cmus mice eat 60% more than control littermates but weigh almost half as much.So I guess that means thier running a fast metabolsim and should live relatively short lives, right?
A second surprising result was the apparent extend longevity of the PEPCK-Cmus mice; they lived almost two years longer than the controls and had normal litters of pups at 30 to 35 months of age (most mice stop being reproductively active at 12 to 18 months).Whoops, guess that theory is out the window now.
levels of hormones and cytokines in the blood of the PEPCK-Cmus mice and noted very low levels of insulin, leptin and MCP-1 as compared to control animalsLow insulin. They say in the study that the low leptin is because they have very low amounts of white fat mass.
We suspect that the major factor responsible for the longevity of the PEPCK-Cmus mice is the very low concentration of insulin in the blood of the mice that is maintained over their lifetime of hyperactivity.Yeh so what was I saying, low insulin.
Anyway, the only question mark in this study is, what is driving the mice to be excessively active? Is it the fact they have a large number of mitochondria? Or is the fact that overexpression of PEPCK-C results in increased cleareance of citric acid cycle waste products?