Flavin-containing monooxygenases: a role in energy homeostasis.
Doctoral thesis, UCL (University College London).
Mice lacking flavin-containing mono-oxygenases (FMOs) genes, Fmos 1, 2 and 4, which are 10-weeks of age, appear healthy, are lean and weigh less than wild-type mice. The knockout mice store less fat in white adipose tissue and have higher HDL cholesterol, glucose and nitric oxide in plasma. Indirect calorimetry results showed that the knockout mice have a higher resting metabolic rate. They also have an increased capacity for voluntary exercise and a higher rate of beta-oxidation in resting soleus muscle. There was no evidence for an increase in adaptive thermogenesis in the knockout mice. Quantitative real-time PCR analysis of mRNAs for several proteins, namely fatty acid synthase, perilipin, TNF-α and NOS indicate that lipogenesis in white fat is reduced, whereas lipolysis is enhanced. There is an increase in the expression of UCP1 and glycerol kinase mRNA in white fat. This, together with no increase in plasma NEFA, triglyceride or glycerol indicates a futile cycle may operate in the white adipose tissue. Glut-4 mRNA expression is decreased in white fat and this may account in part for the higher plasma glucose. The knockout mice have increased urea and creatinine in both plasma and urine indicating an increase in protein breakdown. The knockout mice exhibited an increased in free glucose in their liver. The phenotype of older, 20-week, knockout mice showed age-related changes compared to the 10-week knockout mice. They have a markedly increased food intake, a reduced metabolic rate, and a change in fuel burning, with fat contributing almost equally with carbohydrate and an increase in plasma nitric oxide. The phenotype experiments have revealed that flavin-containing monooxygenases have a role in endogenous metabolism and that there are differences and similarities in the phenotype of knockout mice at 10- and 20-weeks of age.
|Title:||Flavin-containing monooxygenases: a role in energy homeostasis|
|Additional information:||Permission for digitisation not received|
|UCL classification:||UCL > School of Life and Medical Sciences > Faculty of Life Sciences > Biosciences (Division of) > Structural and Molecular Biology|
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