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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

Relative expression and enzymatic activity of DDAHs in the white adipose tissue of GK rats. The extracts of the periepididymal fat pads from 11- (A–C) and 20-week-old (D–F) Wistar (open bars) and GK rats (closed bars) were analyzed for DDAH1 and DDAH2 expression, and total DDAH activity. Representative results are shown in the upper panels. Each bar in the graph represents the mean ± SEM (n = 5–10). The percentile represents the relative level of expression or activity to that of the age-matched Wistar controls. *p ≪ 0.05, **p ≪ 0.01 vs. the controls. IB, immunoblotting.
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Figure 2: Relative expression and enzymatic activity of DDAHs in the white adipose tissue of GK rats. The extracts of the periepididymal fat pads from 11- (A–C) and 20-week-old (D–F) Wistar (open bars) and GK rats (closed bars) were analyzed for DDAH1 and DDAH2 expression, and total DDAH activity. Representative results are shown in the upper panels. Each bar in the graph represents the mean ± SEM (n = 5–10). The percentile represents the relative level of expression or activity to that of the age-matched Wistar controls. *p ≪ 0.05, **p ≪ 0.01 vs. the controls. IB, immunoblotting.

Mentions: The DDAH1 protein level in the tissue extracts from the periepididymal fat of GK rats was increased by 20% at 11 weeks of age and 84% at 20 weeks of age compared with the age-matched controls (p = 0.046 and 0.003, respectively) (Figure 2A and D). In contrast, the DDAH2 protein levels were lower in the tissue of GK rats than in the control rats, with a 34% reduction for 11-week-old and a 30% reduction for 20-week-old rats compared to the corresponding control values (p ≪ 0.001 and p = 0.024, respectively) (Figure 2B and E). The catalytic activities of adipose DDAH in GK rats were 2.5-fold and 3.6-fold greater than the corresponding control values for 11- and 20-week-old rats, respectively (p ≪ 0.001 and p ≪ 0.001, respectively) (Figure 2C and F).


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

Iwasaki H - Diabetol Metab Syndr (2012)

Relative expression and enzymatic activity of DDAHs in the white adipose tissue of GK rats. The extracts of the periepididymal fat pads from 11- (A–C) and 20-week-old (D–F) Wistar (open bars) and GK rats (closed bars) were analyzed for DDAH1 and DDAH2 expression, and total DDAH activity. Representative results are shown in the upper panels. Each bar in the graph represents the mean ± SEM (n = 5–10). The percentile represents the relative level of expression or activity to that of the age-matched Wistar controls. *p ≪ 0.05, **p ≪ 0.01 vs. the controls. IB, immunoblotting.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 2: Relative expression and enzymatic activity of DDAHs in the white adipose tissue of GK rats. The extracts of the periepididymal fat pads from 11- (A–C) and 20-week-old (D–F) Wistar (open bars) and GK rats (closed bars) were analyzed for DDAH1 and DDAH2 expression, and total DDAH activity. Representative results are shown in the upper panels. Each bar in the graph represents the mean ± SEM (n = 5–10). The percentile represents the relative level of expression or activity to that of the age-matched Wistar controls. *p ≪ 0.05, **p ≪ 0.01 vs. the controls. IB, immunoblotting.
Mentions: The DDAH1 protein level in the tissue extracts from the periepididymal fat of GK rats was increased by 20% at 11 weeks of age and 84% at 20 weeks of age compared with the age-matched controls (p = 0.046 and 0.003, respectively) (Figure 2A and D). In contrast, the DDAH2 protein levels were lower in the tissue of GK rats than in the control rats, with a 34% reduction for 11-week-old and a 30% reduction for 20-week-old rats compared to the corresponding control values (p ≪ 0.001 and p = 0.024, respectively) (Figure 2B and E). The catalytic activities of adipose DDAH in GK rats were 2.5-fold and 3.6-fold greater than the corresponding control values for 11- and 20-week-old rats, respectively (p ≪ 0.001 and p ≪ 0.001, respectively) (Figure 2C and F).

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