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Effects of Alpha-Lipoic Acid on Oxidative Stress and Kinin Receptor Expression in Obese Zucker Diabetic Fatty Rats.

Midaoui AE, Talbot S, Lahjouji K, Dias JP, Fantus IG, Couture R - J Diabetes Metab (2015)

Bottom Line: Superoxide anion production was measured by lucigenin chemiluminescence.Alpha-lipoic acid treatment was found to prevent the final body weight increase without affecting significantly hyperglycemia, hyperinsulinemia and insulin resistance index in Zucker Diabetic Fatty rats.The ability of α-lipoic acid to blunt the body weight gain appears to be mediated in part by preventing NADPH oxidase activity rise in adipose tissue and reversing the hepatic upregulation of kinin B1 receptor in Zucker Diabetic Fatty rats.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular and Integrative Physiology, Faculty of Medicine, Université de Montréal, PO Box 6128, Station City-Center, Montréal, Qc, H3C 3J7 Canada.

ABSTRACT

Objective: To investigate the impact of alpha-lipoic acid on superoxide anion production and NADPH oxidase activity as well as on the expression of kinin B1 and B2 receptors in key organs of obese Zucker Diabetic Fatty rats.

Methods: Superoxide anion production was measured by lucigenin chemiluminescence. Kinin B1 and B2 receptors expression was measured at protein and mRNA levels by western blot and qRT-PCR in key organs of Zucker Diabetic Fatty and Zucker lean control rats treated for a period of 6 weeks with a standard diet or a diet containing the antioxidant α-lipoic acid (1 g/kg).

Results: Superoxide anion production and NADPH oxidase activity were significantly enhanced in aorta and adipose tissue of Zucker Diabetic Fatty rats. Kinin B1 and B2 receptors expression levels were also significantly increased in the liver and the gastrocnemius muscle of Zucker Diabetic Fatty rats. Expression of both receptors was not altered in the pancreas of Zucker Diabetic Fatty rats and was undetectable in white retroperitoneal adipose tissue. Alpha-lipoic acid prevented the rise in NADPH oxidase activity in aorta and epididymal adipose tissue of Zucker Diabetic Fatty rats and the upregulation of kinin B1 receptor in liver and gastrocnemius muscle and that of kinin B2 receptor in the liver. Alpha-lipoic acid treatment was found to prevent the final body weight increase without affecting significantly hyperglycemia, hyperinsulinemia and insulin resistance index in Zucker Diabetic Fatty rats.

Conclusion: Findings support the hypothesis that oxidative stress is implicated in the induction of kinin B1 receptor in Zucker Diabetic Fatty rats. The ability of α-lipoic acid to blunt the body weight gain appears to be mediated in part by preventing NADPH oxidase activity rise in adipose tissue and reversing the hepatic upregulation of kinin B1 receptor in Zucker Diabetic Fatty rats.

No MeSH data available.


Related in: MedlinePlus

Effect of 6-week treatment with α-lipoic acid (LA) or standard diet (SD) on the expression of kinin B1R (A, C, E) and B2R (B, D, F) in the gastrocnemius skeletal muscle of 12 weeks Zucker diabetic fatty (ZDF) rats and age-matched Zucker lean (ZL) rats. Shown are mRNA (A, B) and protein (C–F) expression levels of B1R (37 kDa) and B2R (42 kDa). Dynein (75 kDa) and 18S mRNA were used as standards. Data are the mean ± S.E.M of 3–8 rats/group. Statistical comparison with ZL (*) and ZD (+) in SD is indicated by ++ P<0.01; ***,+++ P<0.001.
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Figure 4: Effect of 6-week treatment with α-lipoic acid (LA) or standard diet (SD) on the expression of kinin B1R (A, C, E) and B2R (B, D, F) in the gastrocnemius skeletal muscle of 12 weeks Zucker diabetic fatty (ZDF) rats and age-matched Zucker lean (ZL) rats. Shown are mRNA (A, B) and protein (C–F) expression levels of B1R (37 kDa) and B2R (42 kDa). Dynein (75 kDa) and 18S mRNA were used as standards. Data are the mean ± S.E.M of 3–8 rats/group. Statistical comparison with ZL (*) and ZD (+) in SD is indicated by ++ P<0.01; ***,+++ P<0.001.

Mentions: B1R and B2R mRNA and protein expression levels were significantly increased in the liver (Figure 3) and the gastrocnemius muscle (Figure 4) of ZDF rats in comparison with ZL rats. A 6-week treatment with LA prevented the raised in B1R at mRNA and protein levels in the liver and gastrocnemius of ZDF rats while it had no effect on basal B1R expression in ZL rats (Figures 3 and 4). Protein and mRNA levels of B2R were reversed by LA in the liver but not in the gastrocnemius of ZDF rats (Figures 3 and 4). As shown in Figure 5, protein and mRNA expression levels of B1R and B2R in the pancreas were not significantly different in ZDF in comparison to ZL rats. Moreover, LA treatment had no effect on these parameters in those animals (Figure 5). Both B1R and B2R failed to be detected at mRNA and protein levels in the white adipose tissue of ZL and ZDF rats (Figure 6).


Effects of Alpha-Lipoic Acid on Oxidative Stress and Kinin Receptor Expression in Obese Zucker Diabetic Fatty Rats.

Midaoui AE, Talbot S, Lahjouji K, Dias JP, Fantus IG, Couture R - J Diabetes Metab (2015)

Effect of 6-week treatment with α-lipoic acid (LA) or standard diet (SD) on the expression of kinin B1R (A, C, E) and B2R (B, D, F) in the gastrocnemius skeletal muscle of 12 weeks Zucker diabetic fatty (ZDF) rats and age-matched Zucker lean (ZL) rats. Shown are mRNA (A, B) and protein (C–F) expression levels of B1R (37 kDa) and B2R (42 kDa). Dynein (75 kDa) and 18S mRNA were used as standards. Data are the mean ± S.E.M of 3–8 rats/group. Statistical comparison with ZL (*) and ZD (+) in SD is indicated by ++ P<0.01; ***,+++ P<0.001.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4580416&req=5

Figure 4: Effect of 6-week treatment with α-lipoic acid (LA) or standard diet (SD) on the expression of kinin B1R (A, C, E) and B2R (B, D, F) in the gastrocnemius skeletal muscle of 12 weeks Zucker diabetic fatty (ZDF) rats and age-matched Zucker lean (ZL) rats. Shown are mRNA (A, B) and protein (C–F) expression levels of B1R (37 kDa) and B2R (42 kDa). Dynein (75 kDa) and 18S mRNA were used as standards. Data are the mean ± S.E.M of 3–8 rats/group. Statistical comparison with ZL (*) and ZD (+) in SD is indicated by ++ P<0.01; ***,+++ P<0.001.
Mentions: B1R and B2R mRNA and protein expression levels were significantly increased in the liver (Figure 3) and the gastrocnemius muscle (Figure 4) of ZDF rats in comparison with ZL rats. A 6-week treatment with LA prevented the raised in B1R at mRNA and protein levels in the liver and gastrocnemius of ZDF rats while it had no effect on basal B1R expression in ZL rats (Figures 3 and 4). Protein and mRNA levels of B2R were reversed by LA in the liver but not in the gastrocnemius of ZDF rats (Figures 3 and 4). As shown in Figure 5, protein and mRNA expression levels of B1R and B2R in the pancreas were not significantly different in ZDF in comparison to ZL rats. Moreover, LA treatment had no effect on these parameters in those animals (Figure 5). Both B1R and B2R failed to be detected at mRNA and protein levels in the white adipose tissue of ZL and ZDF rats (Figure 6).

Bottom Line: Superoxide anion production was measured by lucigenin chemiluminescence.Alpha-lipoic acid treatment was found to prevent the final body weight increase without affecting significantly hyperglycemia, hyperinsulinemia and insulin resistance index in Zucker Diabetic Fatty rats.The ability of α-lipoic acid to blunt the body weight gain appears to be mediated in part by preventing NADPH oxidase activity rise in adipose tissue and reversing the hepatic upregulation of kinin B1 receptor in Zucker Diabetic Fatty rats.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular and Integrative Physiology, Faculty of Medicine, Université de Montréal, PO Box 6128, Station City-Center, Montréal, Qc, H3C 3J7 Canada.

ABSTRACT

Objective: To investigate the impact of alpha-lipoic acid on superoxide anion production and NADPH oxidase activity as well as on the expression of kinin B1 and B2 receptors in key organs of obese Zucker Diabetic Fatty rats.

Methods: Superoxide anion production was measured by lucigenin chemiluminescence. Kinin B1 and B2 receptors expression was measured at protein and mRNA levels by western blot and qRT-PCR in key organs of Zucker Diabetic Fatty and Zucker lean control rats treated for a period of 6 weeks with a standard diet or a diet containing the antioxidant α-lipoic acid (1 g/kg).

Results: Superoxide anion production and NADPH oxidase activity were significantly enhanced in aorta and adipose tissue of Zucker Diabetic Fatty rats. Kinin B1 and B2 receptors expression levels were also significantly increased in the liver and the gastrocnemius muscle of Zucker Diabetic Fatty rats. Expression of both receptors was not altered in the pancreas of Zucker Diabetic Fatty rats and was undetectable in white retroperitoneal adipose tissue. Alpha-lipoic acid prevented the rise in NADPH oxidase activity in aorta and epididymal adipose tissue of Zucker Diabetic Fatty rats and the upregulation of kinin B1 receptor in liver and gastrocnemius muscle and that of kinin B2 receptor in the liver. Alpha-lipoic acid treatment was found to prevent the final body weight increase without affecting significantly hyperglycemia, hyperinsulinemia and insulin resistance index in Zucker Diabetic Fatty rats.

Conclusion: Findings support the hypothesis that oxidative stress is implicated in the induction of kinin B1 receptor in Zucker Diabetic Fatty rats. The ability of α-lipoic acid to blunt the body weight gain appears to be mediated in part by preventing NADPH oxidase activity rise in adipose tissue and reversing the hepatic upregulation of kinin B1 receptor in Zucker Diabetic Fatty rats.

No MeSH data available.


Related in: MedlinePlus