Abstract
Obesity is associated with altered glycine metabolism in humans. This study investigated the mechanisms regulating glycine metabolism in obese rats. Eight-week-old Zucker diabetic fatty rats (ZDF; a type-II diabetic animal model) received either 1% glycine or 1.19% l-alanine (isonitrogenous control) in drinking water for 6 weeks. An additional group of lean Zucker rats also received 1.19% l-alanine as a lean control. Glycine concentrations in serum and liver were markedly lower in obese versus lean rats. Enteral glycine supplementation restored both serum and hepatic glycine levels, while reducing mesenteric and internal white fat mass compared with alanine-treated ZDF rats. Blood glucose and non-esterified fatty acid (NEFA) concentrations did not differ between the control and glycine-supplemented ZDF rats (P > 0.10). Both mRNA and protein expression of aminomethyltransferase (AMT) and glycine dehydrogenase, decarboxylating (GLDC) were increased in the livers of obese versus lean rats (P < 0.05). In contrast, glycine cleavage system H (GCSH) hepatic mRNA expression was downregulated in obese versus lean rats, although there was no change in protein expression. These findings indicate that reduced quantities of glycine observed in obese subjects likely results from an upregulation of the hepatic glycine cleavage system and that dietary glycine supplementation potentially reduces obesity in ZDF rats.
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Abbreviations
- ADMA:
-
Asymmetric dimethylarginine
- AGXT:
-
Alanine-glyoxylate aminotransferase
- AMT:
-
Aminomethyltransferase
- DAO:
-
d-amino-acid oxidase
- DLD:
-
Dihydrolipoamide dehydrogenase
- DMGDH:
-
Dimethylglycine dehydrogenase
- EDL:
-
Extensor digitorum longus muscle
- GCAT:
-
Glycine C-acetyltransferase
- GCSH:
-
Glycine cleavage system H
- GLDC:
-
Glycine dehydrogenase (decarboxylating)
- IL:
-
Interleukin
- NEFA:
-
Non-esterified fatty acid
- SARDH:
-
Sarcosine dehydrogenase
- SHMT:
-
Serine hydroxymethyltrasnferase 1
- THA1P:
-
Threonine aldolase 1 pseudogene
- TNF:
-
Tumor necrosis factor
- ZDF:
-
Zucker diabetic fatty
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Acknowledgements
This project was supported by an award from the Mexican and U.S. Latin American Research Center at Texas A&M University (M.C.S.) and by a Grant No. 10GRNT4480020 from American Heart Association (G.W.).
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Simmons, R.M., McKnight, S.M., Edwards, A.K. et al. Obesity increases hepatic glycine dehydrogenase and aminomethyltransferase expression while dietary glycine supplementation reduces white adipose tissue in Zucker diabetic fatty rats. Amino Acids 52, 1413–1423 (2020). https://doi.org/10.1007/s00726-020-02901-9
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DOI: https://doi.org/10.1007/s00726-020-02901-9