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Activities of asymmetric dimethylarginine-related enzymes in white adipose tissue are associated with circulating lipid biomarkers.

Iwasaki H - Diabetol Metab Syndr (2012)

Bottom Line: This dynamic of ADMA-related enzymes in white adipose tissues was distinct from that of skeletal muscle tissue.In all subjects the adipose PRMT1 and DDAH activities were statistically correlated with the levels of serum NEFA and TG.Changes in adipose ADMA-related enzymes might play a part in the function of white adipose tissue.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Internal Medicine, Division of Endocrinology and Metabolism, Toshiba Rinkan Hospital, 7-9-1 Kami-tsuruma, Minami-ku, Sagamihara, Kanagawa, 252-0385, Japan. iwasaki.har@gmail.com.

ABSTRACT

Background: Asymmetric NG,NG-dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase, is regulated by the enzymatic participants of synthetic and metabolic processes, i.e., type I protein N-arginine methyltransferase (PRMT) and dimethylarginine dimethylaminohydrolase (DDAH). Previous reports have demonstrated that circulating ADMA levels can vary in patients with type 1 and type 2 diabetes mellitus (T2DM). White adipose tissue expresses the full enzymatic machinery necessary for ADMA production and metabolism; however, modulation of the activities of adipose ADMA-related enzymes in T2DM remains to be determined.

Methods: A rodent model of T2DM using 11- and 20-week old Goto-Kakizaki (GK) rats was used. The expression and catalytic activity of PRMT1 and DDAH1 and 2 in the white adipose tissues (periepididymal, visceral and subcutaneous fats) and femur skeletal muscle tissue were determined by immunoblotting, in vitro methyltransferase and in vitro citrulline assays.

Results: Non-obese diabetic GK rats showed low expression and activity of adipose PRMT1 compared to age-matched Wistar controls. Adipose tissues from the periepididymal, visceral and subcutaneous fats of GK rats had high DDAH1 expression and total DDAH activity, whereas the DDAH2 expression was lowered below the control value. This dynamic of ADMA-related enzymes in white adipose tissues was distinct from that of skeletal muscle tissue. GK rats had lower levels of serum non-esterified fatty acids (NEFA) and triglycerides (TG) than the control rats. In all subjects the adipose PRMT1 and DDAH activities were statistically correlated with the levels of serum NEFA and TG.

Conclusion: Activities of PRMT1 and DDAH in white adipose tissues were altered in diabetic GK rats in an organ-specific manner, which was reflected in the serum levels of NEFA and TG. Changes in adipose ADMA-related enzymes might play a part in the function of white adipose tissue.

No MeSH data available.


Related in: MedlinePlus

Correlation analysis of the relationships between the activities of ADMA-related enzymes and lipid biomarker levels. The values of the parameters are depicted for 11-week-old Wistar (open circles) and GK rats (closed circles) in Figure 1B, Figure 2C and Table 2. The lines show linear regressions for the parameters indicated in each graph. The Pearson’s correlation coefficients (R2) and p values for each correlation are also indicated in the graph.
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Figure 3: Correlation analysis of the relationships between the activities of ADMA-related enzymes and lipid biomarker levels. The values of the parameters are depicted for 11-week-old Wistar (open circles) and GK rats (closed circles) in Figure 1B, Figure 2C and Table 2. The lines show linear regressions for the parameters indicated in each graph. The Pearson’s correlation coefficients (R2) and p values for each correlation are also indicated in the graph.

Mentions: Characteristics of Wistar control and GK diabetic rats at 11 and 20 weeks of age are shown in Table 2. Both 11- and 20-week-old GK rats were equivalent to the age-matched Wistar controls in body-weight (p = 0.408 and p = 0.496, respectively). During the postprandial state, the serum levels of NEFA were lower in 11- and 20-week-old GK rats compared to the age-matched Wistar controls (p = 0.027 and p = 0.002, respectively). GK rats also exhibited lower TG levels compared to the corresponding control values (p ≪ 0.001 for 11-week-old and p ≪ 0.001 for 20-week-old). For all 11-week-old subjects, a significant positive linear correlation was observed between PRMT1 activity and serum NEFA or TG level (p = 0.025 and p = 0.017, respectively) (Figure 3A and B). A negative correlation was also observed between DDAH activity and the serum NEFA or TG level (p = 0.001 and p ≪ 0.001, respectively) (Figure 3C and D).


Activities of asymmetric dimethylarginine-related enzymes in white adipose tissue are associated with circulating lipid biomarkers.

Iwasaki H - Diabetol Metab Syndr (2012)

Correlation analysis of the relationships between the activities of ADMA-related enzymes and lipid biomarker levels. The values of the parameters are depicted for 11-week-old Wistar (open circles) and GK rats (closed circles) in Figure 1B, Figure 2C and Table 2. The lines show linear regressions for the parameters indicated in each graph. The Pearson’s correlation coefficients (R2) and p values for each correlation are also indicated in the graph.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3472189&req=5

Figure 3: Correlation analysis of the relationships between the activities of ADMA-related enzymes and lipid biomarker levels. The values of the parameters are depicted for 11-week-old Wistar (open circles) and GK rats (closed circles) in Figure 1B, Figure 2C and Table 2. The lines show linear regressions for the parameters indicated in each graph. The Pearson’s correlation coefficients (R2) and p values for each correlation are also indicated in the graph.
Mentions: Characteristics of Wistar control and GK diabetic rats at 11 and 20 weeks of age are shown in Table 2. Both 11- and 20-week-old GK rats were equivalent to the age-matched Wistar controls in body-weight (p = 0.408 and p = 0.496, respectively). During the postprandial state, the serum levels of NEFA were lower in 11- and 20-week-old GK rats compared to the age-matched Wistar controls (p = 0.027 and p = 0.002, respectively). GK rats also exhibited lower TG levels compared to the corresponding control values (p ≪ 0.001 for 11-week-old and p ≪ 0.001 for 20-week-old). For all 11-week-old subjects, a significant positive linear correlation was observed between PRMT1 activity and serum NEFA or TG level (p = 0.025 and p = 0.017, respectively) (Figure 3A and B). A negative correlation was also observed between DDAH activity and the serum NEFA or TG level (p = 0.001 and p ≪ 0.001, respectively) (Figure 3C and D).

Bottom Line: This dynamic of ADMA-related enzymes in white adipose tissues was distinct from that of skeletal muscle tissue.In all subjects the adipose PRMT1 and DDAH activities were statistically correlated with the levels of serum NEFA and TG.Changes in adipose ADMA-related enzymes might play a part in the function of white adipose tissue.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Internal Medicine, Division of Endocrinology and Metabolism, Toshiba Rinkan Hospital, 7-9-1 Kami-tsuruma, Minami-ku, Sagamihara, Kanagawa, 252-0385, Japan. iwasaki.har@gmail.com.

ABSTRACT

Background: Asymmetric NG,NG-dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase, is regulated by the enzymatic participants of synthetic and metabolic processes, i.e., type I protein N-arginine methyltransferase (PRMT) and dimethylarginine dimethylaminohydrolase (DDAH). Previous reports have demonstrated that circulating ADMA levels can vary in patients with type 1 and type 2 diabetes mellitus (T2DM). White adipose tissue expresses the full enzymatic machinery necessary for ADMA production and metabolism; however, modulation of the activities of adipose ADMA-related enzymes in T2DM remains to be determined.

Methods: A rodent model of T2DM using 11- and 20-week old Goto-Kakizaki (GK) rats was used. The expression and catalytic activity of PRMT1 and DDAH1 and 2 in the white adipose tissues (periepididymal, visceral and subcutaneous fats) and femur skeletal muscle tissue were determined by immunoblotting, in vitro methyltransferase and in vitro citrulline assays.

Results: Non-obese diabetic GK rats showed low expression and activity of adipose PRMT1 compared to age-matched Wistar controls. Adipose tissues from the periepididymal, visceral and subcutaneous fats of GK rats had high DDAH1 expression and total DDAH activity, whereas the DDAH2 expression was lowered below the control value. This dynamic of ADMA-related enzymes in white adipose tissues was distinct from that of skeletal muscle tissue. GK rats had lower levels of serum non-esterified fatty acids (NEFA) and triglycerides (TG) than the control rats. In all subjects the adipose PRMT1 and DDAH activities were statistically correlated with the levels of serum NEFA and TG.

Conclusion: Activities of PRMT1 and DDAH in white adipose tissues were altered in diabetic GK rats in an organ-specific manner, which was reflected in the serum levels of NEFA and TG. Changes in adipose ADMA-related enzymes might play a part in the function of white adipose tissue.

No MeSH data available.


Related in: MedlinePlus