Nutr Res Pract.  2010 Feb;4(1):23-29.

Effects of poly-gamma-glutamic acid on serum and brain concentrations of glutamate and GABA in diet-induced obese rats

Affiliations
  • 1Department of Foods and Nutrition, Kookmin University, 861-1 Jeongneung-dong, Seongbuk-gu, Seoul 136-702, Korea. shkim@kookmin.ac.kr

Abstract

Poly-gamma-glutamic acid (gamma-PGA) is a mucilaginous and biodegradable compound produced by Bacillus subtilis from fermented soybeans, and is found in the traditional Korean soy product, cheongkukjang. This study was carried out to evaluate the effects of gamma-PGA from a food source on the concentration of the neurotransmitter GABA and its metabolic precursor glutamate in diet-induced obese rats. Eight-week old male Sprague-Dawley rats (n=60) were used. The rats were divided into two groups and obesity was induced by providing either a 10% control fat or 45% high fat diet for 5 weeks. The rats were then blocked into 6 groups and supplemented with a 0.1% gamma-PGA diet for 4 weeks. After sacrifice, brain and serum GABA and glutamate concentrations were analyzed by high performance liquid chromatography with fluorometric detection. The rats fed the high fat diet had significantly increased body weights. gamma-PGA supplementation significantly increased serum concentrations of glutamate and GABA in the control fat diet groups while this effect was not found in the high fat groups. In the brain, glutamate concentrations were significantly higher in the gamma-PGA supplemented groups both in rats fed the normal and high fat diets than in the no gamma-PGA controls. GABA concentrations showed the same tendency. The results indicated that gamma-PGA intake increased GABA concentrations in the serum and brain. However, the effects were not shown in obese rats.

Keyword

Poly-gamma-glutamic acid (gamma-PGA); glutamate; gamma-aminobutyric acid (GABA)

MeSH Terms

Animals
Bacillus subtilis
Body Weight
Brain
Chromatography, Liquid
Diet
Diet, High-Fat
gamma-Aminobutyric Acid
Glutamic Acid
Humans
Male
Neurotransmitter Agents
Obesity
Polyglutamic Acid
Rats
Rats, Sprague-Dawley
Soybeans
Glutamic Acid
Neurotransmitter Agents
Polyglutamic Acid
gamma-Aminobutyric Acid

Figure

  • Fig. 1 Changes of body weight during the experimental period. CC: 10% fat control, CP: 10% fat with γ-PGA, HC: High fat control, HP: High fat with γ-PGA, HCC: 45% to 10% fat control, HCP: 45% to 10% fat with γ-PGA. All points represent means, n=10 rats per group. Different letters in the same week indicate significantly different values assessed by Duncan's multiple range test (P < 0.05).

  • Fig. 2 Chromatograms of NDA derivatives of glutamate and GABA. (A) Standard solution, 10 ug of glutamate (retention time: 3.752 min) and GABA (retention time: 8.338 min) injected onto the column. Conditions as described in the text. (B) Example of a brain sample from a CP group rat showing glutamate (8.8 mg/g tissue) and GABA (1.6 mg/g tissue).

  • Fig. 3 Chromatograms of OPA derivatives of glutamate and GABA. (A) Standard solution, 10 ug of glutamate (retention time: 1.833 min) and GABA (retention time: 2.478 min) injected onto the column. Conditions as described in the text. (B) Example of a serum sample from a CP group rat showing glutamate (9.8 ug/ml) and GABA (60.4 ug/ml).


Reference

1. Meldrum BS. Glutamate as a neurotransmitter in the brain: review of physiology and pathology. J Nutr. 2000. 130:1007S–1015S.
Article
2. Hawkins RA. The blood-brain barrier and glutamate. Am J Clin Nutr. 2009. 90:867S–874S.
Article
3. Wong CGT, Bottiglieri T, Snead OC III. GABA, γ-hydroxybutric acid, and neurological disease. Ann Neurol. 2003. 53:S3–S12.
4. Bown AW, Shelp BJ. The metabolism and functions of [gamma]-aminobutyric acid. Plant Physiol. 1997. 155:1–5.
Article
5. Shelp BJ, Bown AW, Mclean MD. Metabolism and functions of gamma-aminobutyric acid. Trends Plant Sci. 1999. 4:446–452.
Article
6. Petroff OAC. GABA and glutamate in the human brain. Neuroscientist. 2002. 8:562–573.
7. Gavin JR, Saltman RJ, Tollefsen SE. Growth hormone receptors in isolated rat adipocytes. Endocrinology. 1982. 110:637–643.
Article
8. Schneider HJ, Oertel H, Hurck M, Pollmächer T, Stalla GK, Steiger A. Night sleep EEG and daytime sleep propensity in adult hypopituitary patients with growth hormone deficiency before and after six months of growth hormone replacement. Psychoneuroendocrinology. 2005. 30:29–37.
Article
9. Li H, Cho JY, Gao TC, Choi CR, Lee KD, Cho JE, Cho GS, Ham K-S. Increment of physiologically active compounds in germinated brown rice treated with chitosan and its effect on obesity of rat fed a high fat diet. Journal of the Korean Society of Food Science and Nutrition. 2008. 37:985–991.
Article
10. Oh SH, Kim HJ, Kim YH, Yu JJ, Park KB, Jeon JI. Changes in some physic-chemical properties and γ-aminobutyric acid content of kimchi during fermentation and storage. J Food Sci Nutr. 2008. 13:219–224.
Article
11. Ren J, Zhu BH, Relling DP, Esberg LB, Ceylan-Isik AF. High-fat diet-induced obesity leads to resistance to leptin-induced cardiomyocyte contractile response. Obesity (Silver Spring). 2008. 16:241–223.
Article
12. Schrauwen P, Westerterp KR. The role of high-fat diets and physical activity in the regulation of body weight. Br J Nutr. 2000. 84:417–427.
Article
13. Inoue K, Shirai T, Ochiai H, Kasao M, Hayakawa K, Kimura M, Sansawa H. Blood-pressure-lowering effect of a novel fermented milk containing γ-aminobutyric acid (GABA) in mild hypertensives. Eur J Clin Nutr. 2003. 57:490–495.
Article
14. Kang SE, Rhee JH, Park C, Sung MH, Lee IH. Distribution of poly-γ-glutamate (γ-PGA) producers in Korean fermented foods, Cheongkukjang, Doenjang, and Kochujang. Food Sci Biotechnol. 2005. 14:704–708.
15. Lee MS, Jang JI, Kim HS. Effect of γ-PGA (Poly-γ-glutamic acid) supplement on calcium absorption and bone metabolism in rats. Journal of the Korean Society of Food Science and Nutrition. 2006. 35:255–261.
Article
16. Kim TW, Lee TY, Bae HC, Hahm JH, Kim YH, Park C, Kang TH, Kim CJ, Sung MH, Poo HY. Oral administration of high molecular mass poly-γ-glutamate induces NK cell-mediated antitumor immunity. J Immunol. 2007. 179:775–780.
Article
17. Relling DP, Esberg LB, Cindy X, Johnson WT, Murphy EJ, Carlson EC, Saari JT, Ren J. High-fat-diet-induced juvenile obesity leads to cardiomyocyte dysfunction and upregulation of Foxo3a transcription factor independent of lipotoxicity and apoptosis. J Hypertens. 2006. 24:549–561.
Article
18. Thakker GD, Frangogiannis NG, Bujak M, Zymek P, Gaubatz JW, Reddy AK, Taffet G, Michael LH, Entman ML, Ballantyne CM. Effects of diet-induced obesity on inflammation and remodeling after myocardial infarction. Am J Physiol Heart Circ Physiol. 2006. 291:H2504–H2514.
Article
19. Levin BE, Govek EK, Dunn-Meynell AA. Reduced glucose-induced neuronal activation in the hypothalamus of diet-induced obese rats. Brain Res. 1998. 808:317–319.
Article
20. Landerberg L. Obesity, metabolism and hypertension. Yale J Biol Med. 1989. 62:511–519.
21. Park YJ, Lee WC, Yim HW, Park YM. The association between sleep and obesity in Korean Adults. J Prev Med Public Health. 2007. 40:454–460.
Article
22. Verona RD, Winn MP, Babineau TW, Eng BP, Feldman HR, Ware JC. Overweight and obese patients in a primary care population report less sleep than patients with a normal body mass index. Arch Intern Med. 2005. 165:25–30.
Article
23. Clarke G, O'Mahony S, Malone G, Dinan TG. An isocratic high performance liquid chromatography method for the determination of GABA and glutamate in discrete regions of the rodent brain. J Neurosci Methods. 2007. 160:223–230.
Article
24. Vermeij TAC, Edelbroek PM. Simultaneous high-performance liquid chromatographic analysis of pregabalin, gabapectin and vigabatrin in human serum by precolumn derivatization with o-phataldialdehyde and fluorescence detection. J Chromatogr B Analyt Technol Biomed Life Sci. 2004. 810:297–303.
Article
25. Tanimoto H, Mori M, Motoki M, Torii K, Kaeowaki M, Noguchi T. Natto mucilage containing poly-γ-glutamic acid increases soluble calcium in the rat small intestine. Biosci Biotechnol Biochem. 2001. 65:516–521.
Article
26. Tcherkas YV, Denisenko AD. Simultaneous determination of several amino acids, including homocysteine, cysteine and glutamic acid, in human plasma by isocratic reversed-phase high performance liquid chromatography with fluorimetric detection. J Chromatogr A. 2001. 913:309–313.
Article
27. Terrlink T, van Leeuwen PA, Houdijk A. Plasma amino acids determined by liquid chromatography within 17 minutes. Clin Chem. 1994. 40:245–249.
Article
28. Wang L, Maher TJ, Wurtman RJ. Oral L-glutamine increases GABA levels in striatal tissue and extracellular fluid. FASEB J. 2007. 21:1227–1232.
Article
29. Park JH, Han SH, Shin MK, Park KH, Li KC. Effect of hypertention falling of functional GABA green tea. Korean Journal of Medicinal Crop Science. 2002. 10:37–40.
30. Aoki H, Furuya Y, Endo Y, Fujimoto K. Effect of γ-aminobutyric acid-enriched tempeh-like fermented soybean (GABA-Tempeh) on the blood pressure of spontaneously hypertensive rats. Biosci Biotechnol Biochem. 2003. 67:1806–1808.
Article
31. Oh SH. Effects and applications of germinated brown rice with enhanced levels of GABA. Food Science and Industry. 2007. 40:41–46.
32. Hayakawa K, Kimura M, Kamata K. Mechanism underlying γ-aminobutyric acid-induced antihypertensive effect in spontaneously hypertensive rats. Eur J Pharmacol. 2002. 438:107–113.
Article
33. Sasaki K, Hatta S, Haga M, Oshika H. Effects of bilobalide on γ-aminobutyric acid levels and glutamic acid decarboxylase in mouse brain. Eur J Pharmacol. 1999. 367:165–173.
Article
34. Reeves PG, Nielsen FH, Fahey GC. AIN-93 purified diets for laboratory rodents: Final report of the American Institute of Nutrition Ad Hoc Writing Committee on the reformulation of the AIN-76A rodent diet. J Nutr. 1993. 123:1939–1951.
Article
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