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Deficiency of Type I Platelet-Activating Factor-Acetylhydrolase Catalytic Subunits Causes an Increase in Body Weight
Yasuhiro Nakamura1, Momoko Yoshida2, Kazunari Tanigawa1
1Faculty of Pharma-sciences, Teikyo University.
Insights
Mice lacking type I platelet-activating factor-acetylhydrolase (PAF-AH) catalytic subunits showed increased body weight and food intake. This was associated with significantly decreased testosterone levels in knockout mice, suggesting a link between PAF-AH deficiency and male reproductive hormone levels.
Area of Science:
- Biochemistry
- Endocrinology
- Genetics
Background:
- Type I platelet-activating factor-acetylhydrolase (PAF-AH) is a complex enzyme with unknown physiological functions.
- Its catalytic subunits (α1 and/or α2) associate with a regulatory subunit (β).
Purpose of the Study:
- To investigate the physiological role of type I PAF-AH catalytic subunits.
- To determine the phenotype of knockout mice lacking these subunits compared to wild-type mice.
Main Methods:
- Comparison of body weight and food intake between knockout and control mice.
- Measurement of serum and testis testosterone levels using liquid chromatography-tandem mass spectrometry.
Main Results:
- Knockout mice exhibited significantly increased body weight and food intake from 6 to 20 weeks of age.
- A decrease in testis weight was observed in knockout mice.
- Serum and testis testosterone levels were significantly reduced in knockout mice compared to controls.
Conclusions:
- Deficiency in type I PAF-AH catalytic subunits leads to increased body weight in male mice.
- Reduced testosterone levels contribute to the observed increase in body weight.
- Type I PAF-AH plays a role in regulating body weight and testosterone levels in males.
Abstract:
Type I platelet-activating factor-acetylhydrolase (PAF-AH) forms a complex consisting of two catalytic subunits (α1 and/or α2) with a regulatory subunit (β). Although this protein was discovered as an enzyme that degrades an acetyl ester linked at the sn-2 position of platelet-activating factor (PAF), its physiological function remains unknown. In this study, to examine whether knockout mice lacking the catalytic subunits of this enzyme showed a different phenotype from that of wild-type mice, we measured and compared the body weights of knockout mice and control mice. The body weights of knockout mice were significantly increased compared to those of the control mice during 6 to 20 weeks from birth. Food intake was also significantly increased in knockout mice compared with control mice during these periods. Since a decrease in testis weight was reported in the knockout mice, we expected a decrease in testosterone levels. We measured and compared the amounts of testosterone in the serum and testis of knockout and control mice using liquid chromatography-tandem mass spectrometry, and found that testosterone levels in both the serum and testis were significantly decreased in the knockout mice compared with the control mice. These results suggest that a deficiency of type I PAF-AH catalytic subunits causes an increase in body weight, in part, due to reduced testosterone levels in male mice.
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