A Study of the Effect on Obesity and dyslipidemia in Kidney-hypofunction Animal Model Induced by Unilateral Ureteral Obstruction

Article information

J Korean Med. 2018;39(2):1-12

Publication date (electronic) : 2018 June 30

doi : https://doi.org/10.13048/jkm.18011

Jinyoung Kwak ¹, Junghwan Park ¹, Youngmee Koh ¹, Taekwon Ahn ¹

¹Dept. of Sasang Constitutional Medicine, College of Korean Medicine, Daejeon University

Correspondence to: 안택원(Taekwon Ahn) Dept. of Sasang Constitutional Medicine, Daejeon Univ. Cheonan Hospital of Korean Medicine. Notaesan-ro 4, Seobuk-gu, Cheonan city, Chungcheongnamdo, 31099(Zip code), Korea. Tel: +82-41-521-7535, Fax: +82-41-521-7007, E-mail: twahn@dju.kr

Received 2018 March 15; Revised 2018 May 5; Accepted 2018 June 4.

Abstract

Objectives

The objective of this study is to develop a new animal model with Kidney-hypofunction for Sasang Constitutional Medicine, especially for partial Soyangin(one of four constitution which has good digestive function and poor renal function) by Unilateral Ureteral Obstruction, and to estimate the factor related to obesity, dyslipidemia, and metabolic syndrome.

Methods

The C57BL/6J mice were divided into 3 groups: normal group, high fat diet(HFD) control group, and HFD group with Unilateral Ureteral Obstruction(UUO). Then, the HFD control group and the experimental group were fed with high fat diet for 6 weeks. Food intake and body weight were measured at regular time by week. After the final experiment, blood was gathered for bloodchemical examination and organs(liver, fatty tissue) were remoed, weighted, and mRNA was analyzed with real-time PCR.

Results

The weight growth rate with High fat diet went down by 8.35% in experimental group and had similar FER with the normal group, while HFD control group had higher weight growth rate and FER than any other groups. Also The experimental group had lower triglyceride and LDL cholesterol rate and higher glucose rate in serum. and in mRNA expression, GLUT-9, the protein related to excretion of uric acid and metabolic syndrome, expressed lower rate than that of HFD control group. and IL-6, a kind of cytokine related to obesity and metabolic syndrome, expressed more than HFD control group.

Conclusions

It was found that Kidney-hypofunction animal-experimental model is susceptible to metabolic syndrome.

Keywords: Obesity; Soyangin; Animal-Experimental Model; High-fat Diet

Fig. 1

radical nephrectomy and UUO establishment

Fig. 2

Body weight change in HFD-induced obese mice, and -renal cortex of each study group(UUO: unilateral ureteral obstruction) obese mice.

C57bl/6J-Nr: C57bl/6J normal group (n=5) HFD-CTL: High Fat Diet-Negative Control (n=5)

UUO_HFD-CTL: High Fat Diet group with unilateral ureteral obstruction (n=5)

Fig. 3

Food efficiency ratio (FER, %) in HFD-induced obese mice, and -renal cortex of each study group(UUO: unilateral ureteral obstruction) obese mice.

C57bl/6J-Nr: C57bl/6J normal group (n=5) HFD-CTL: High Fat Diet-Negative Control (n=5)

UUO_HFD-CTL: High Fat Diet group with unilateral ureteral obstruction (n=5)

Fig. 4

AST, ALT level in serum of HFD-induced obese mice, and -renal cortex of each study group(UUO: unilateral ureteral obstruction) obese mice.

C57bl/6J-Nr: C57bl/6J normal group (n=5) HFD-CTL: High Fat Diet-Negative Control (n=5)

UUO_HFD-CTL: High Fat Diet group with unilateral ureteral obstruction (n=5)

Fig. 5

Creatine level in serum of HFD-induced obese mice, and -renal cortex of each study group(UUO: unilateral ureteral obstruction) obese mice.

C57bl/6J-Nr: C57bl/6J normal group (n=5) HFD-CTL: High Fat Diet-Negative Control (n=5) UUO_HFD-CTL: High Fat Diet group with unilateral ureteral obstruction (n=5)

Fig. 6

Total Cholesterol level in serum of HFD-induced obese mice, and -renal cortex of each study group(UUO: unilateral ureteral obstruction) obese mice.

C57bl/6J-Nr: C57bl/6J normal group (n=5) HFD-CTL: High Fat Diet-Negative Control (n=5) UUO_HFD-CTL: High Fat Diet group with unilateral ureteral obstruction (n=5)

Fig. 7

HDL and LDL Cholesterol level in serum of HFD-induced obese mice, and -renal cortex of each study group(UUO: unilateral ureteral obstruction) obese mice.

C57bl/6J-Nr: C57bl/6J normal group (n=5) HFD-CTL: High Fat Diet-Negative Control (n=5) UUO_HFD-CTL: High Fat Diet group with unilateral ureteral obstruction (n=5)

Fig. 8

Triglyceride level in serum of HFD-induced

Fig. 9

Glucose level in serum of HFD-induced obese mice, and -renal cortex of each study group(UUO: unilateral ureteral obstruction) obese mice.

C57bl/6J-Nr: C57bl/6J normal group (n=5) HFD-CTL: High Fat Diet-Negative Control (n=5) UUO_HFD-CTL: High Fat Diet group with unilateral ureteral obstruction (n=5)

Fig. 10

Abdominal subcutaneous fat and Epididymal adipose tissue weight in HFD-induced obese mice, and -renal cortex of each study group(UUO: unilateral ureteral obstruction) obese mice.

C57bl/6J-Nr: C57bl/6J normal group (n=5) HFD-CTL: High Fat Diet-Negative Control (n=5) UUO_HFD-CTL: High Fat Diet group with unilateral ureteral obstruction (n=5)

Fig. 11

Liver weight in HFD-induced obese mice, and -renal cortex of each study group(UUO: unilateral ureteral obstruction) obese mice.

C57bl/6J-Nr: C57bl/6J normal group (n=5) HFD-CTL: High Fat Diet-Negative Control (n=5) UUO_HFD-CTL: High Fat Diet group with unilateral ureteral obstruction (n=5)

Fig. 12

mRNA expression of GLUT-9, IL-6, COX-2 were measured with Real Time-PCR analysis.

C57bl/6J: C57bl/6J normal group (n=5)

HFD-CTL: High Fat Diet-Negative Control (n=5)

UUO_HFD-CTL: High Fat Diet group with unilateral ureteral obstruction (n=5)

Table 1

Food Intake, Body Weight gain, Food Efficiency Ratio in HFD-Fed Obese Mice, and -Renal Cortex of Each Study Group(UUO: Unilateral Ureteral Obstruction) Obese Mice.

References

1. Lee JM. Dongeisusebowon 2nd revth ed. Seoul: Yeogang; 2003. 36p. 278. (Korean).

2. Hwang MW. The lecture of Sasang constitution 2nd Editionth ed. Seoul: Koonja; 2012. p. 33–40. (Korean).

3. Dept of Sasang Constitutional Medicine. All colleges of Korean med in Korea(compilation). The revised and enlarged Sasang Constitutional Medicine Seoul: Jipmoondang; 2012. p. 136–144. (Korean).

4. Hwang MW, Koh BH. The Study on the Pathology of Soyangin in Sasang Constitutional Medicine(SCM). Journal of Sasang Constitutional Medicine 2009;21(3):1–16.

5. Lalich JJ, Burkholder PM, Paik WC. Protein overload nephropathy in rats with unilateral nephrectomy. A correlative light immunogluorescence and electron microscopical analysis. Archives of pathology 99(2)1975;:72–79.

6. Park SB. The Relation of Cardiovascular Risk Factors to Metabolic Syndrome. Journal of the Korean Academy of Family Med 2005;26(10):20–26.

7. Sim JY, Kang HT, Kim SY, Kim JS, Kim JW, Kim JY, et al. The Prevention and Treatment of Metabolic Syndrome in Korean Adults. Korean Journal of Family Practice 2015;5(3):375–420.

8. Perk J, De Backer G, Gohlke H, Graham I, Reiner Z, Verschuren M, et al. European Guidelines on cardiovascular disease prevention in clinical practice (version 2012). The Fifth Joint Task Force of the European Society of Cardiology and Other Societies on Cardiovascular Disease Prevention in Clinical Practice (constituted by representatives of nine societies and by invited experts). Eur Heart J 2012;33:1635–701.

9. Lee TG, Hwang MW, Lee SK, Choe BK, Koh BH, Song IB. A Study on the Prevalence and Risk Factors of the Metabolic Syndrome according to Sasang Constitution. Journal of Korean Med 2006;27(2):14–22.

10. Kim DR. A Study on 4 Type Constitution and Life Character of Obese Patients. Journal of Sasang Constitutional Medicine 1997;9(1):303–313.

11. Yang SM. Association between Risk Factors and Prevalence of Metabolic Syndrome according to Sasang Constitution in Wonju Cohort Study. Doc of Sangji Univ 2007;

12. Choi JW, Yu JS. Cut-off Values of Waist Circumference and Body Mass Index for Metabolic Syndrome according to Sasang Constitution. Journal of Sasang Constitutional Medicine 2014;26(4):365–378.

13. Choi KJ. A Study on the Influence of Sasang Constitution on Insulin Resistance. Doc of Kyunghee Univ 2010;

14. Lee JW, Jang HS, Park BJ, Lee EJ, Koh BH, Lee JH. Can the Sasang Constitutional Type Trait Act as an Independent Risk Factor for Dyslipidemia? Journal of Korean Med. Obesity Research 2014;14(2):63–71.

15. Kim YH, Park JH, Kwak JY, Park JM, Ahn TW. A Study of the Effect on Obesity in Taeeumin Animal-experimental Model Induced Lung Fibrosis with Bleomycin. Journal of Sasang Constitutional Medicine 2016;28(2):147–162.

16. Park JH, Kim YH, Kwak JY, Hong SJ, Park JM, Ahn TW. A study on the effect on obesity and lipid metabolism in liver hypofunction animal-experimental model induced by Acetaminophen(AAP) injection. Journal of Korean Med 2016;37(3):47–61.

17. Kim KB, Park SO. 2001;A study of the correlation of stress and powerlessness based on hemodialysis patients’ constitution of the Korea. Journal of East-West Nursing Research 6(1):7–22.

18. Kim JD. 上壽如水: My Sassang constitution and characteristic 4. pastoral information 3(4)2010;:102–104.

19. Kim BH, Joe DY, Lee SH, Park SE, Ga MK. Generation Sasang Constitution Diagnosis and Classification Using Acoustics Analysis Element. Korea information and communications society 2006;:614–617.

20. Park GS, Han JS, Kim HJ. Effect of Diet Contents on Serum Composition and Urinary Excretion in Female Students according to Sasang Constitution. J East Asian Soc Dietary Life 1998;8(3):271–279.

21. Moon SH, Sin SH, Kim HJ, Kim JY. A Relationship of the Obesity and Body Composition Analysis by Sasang Constitution. Journal of Korean Rehabilitation Med 2002;12(4):1–10.

22. Ucero AC, Benito-Martin A, Izquierdo MC, Sanchez-Niño MD, Sanz AB, Ramos AM, et al. Unilateral ureteral obstruction: beyond obstruction. Int Urol Nephrol 2014;46(4):765–776.

23. Hwang GH, Noh YH, Heo YR. A Study on Hyperlipidemia in Koreans - Specially Related to Hematological Characteristics and Risk Factors of Hypercholesterolemia. Journal of the Korean Society of Food Science and Nutrition 1999;28(3):710–721.

24. Lee HJ, Shin GJ, Park SH, Cho HK. Insulin Resistance and Visceral Fat Obesity in Hyperlipidemia. Korean Circulation Journal 1999;29(7):673–679.

25. Byrne CD, Brindel NPJ, Wang TWM, Hales CN. Interaction of non-esterified fatty acid and insulin in control of triacylglycerol secretion by Hep G2 cells. J Biochem 1991;280:99–104.

26. Randle PF, Garland PB, Hales CN, Newsholme EA. The glucose fatty-acid cycle in obesity and maturity onset diabetes mellitus. Ann NY Acad Sci 1965;131:324–33.

27. Yoon HJ, Lee YH, Cha BS. Causal Relationship of Non-alcoholic Fatty Liver Disease with Obesity and Insulin Resistance. Journal of Korean Diabetes 2014;15:76–81.

28. DeBosch BJ, Kluth O, Fujiwara H, Schürmann A, Moley K. Early-onset metabolic syndrome in mice lacking the intestinal uric acid transporter SLC2A9. Nat Commun 2014;5:4642.

29. Shin YT, Kim KK, Hwang IC. Clinical Implication of Plasma Uric Acid Level. Korean Journal of Family Medicine 2009;30(9):670–680.

30. Quinones Galvan A, Natali A, Baldi S, Frascerra S, Sanna G, Ciociaro D, et al. Effect of insulin on uric acid excretion in humans. Am J Physiol 1995;268:1–5.

31. Eder K, Baffy N, Falus A, Fulop AK. The major inflammatory mediator interleukin-6 and obesity. Inflamm Res 2009;58(11):727–736.

32. Sindhu S, Thomas R, Shihab P, Sriraman D, Behbehani K, Ahmad R. Obesity Is a Positive Modulator of IL-6R and IL-6 Expression in the Subcutaneous Adipose Tissue: Significance for Metabolic Inflammation. PLos One 2015;10(7):e0133494.

33. Stouthard JM, Romijn JA, Van der Poll T, et al. Endocrinologic and metabolic effects of interleukin-6 in humans. Am J Physiol 1995;268:813–319.

Article information Continued

Fig. 1

radical nephrectomy and UUO establishment

Fig. 2

Body weight change in HFD-induced obese mice, and -renal cortex of each study group(UUO: unilateral ureteral obstruction) obese mice.

C57bl/6J-Nr: C57bl/6J normal group (n=5) HFD-CTL: High Fat Diet-Negative Control (n=5)

UUO_HFD-CTL: High Fat Diet group with unilateral ureteral obstruction (n=5)

Fig. 3

Food efficiency ratio (FER, %) in HFD-induced obese mice, and -renal cortex of each study group(UUO: unilateral ureteral obstruction) obese mice.

C57bl/6J-Nr: C57bl/6J normal group (n=5) HFD-CTL: High Fat Diet-Negative Control (n=5)

UUO_HFD-CTL: High Fat Diet group with unilateral ureteral obstruction (n=5)

Fig. 4

AST, ALT level in serum of HFD-induced obese mice, and -renal cortex of each study group(UUO: unilateral ureteral obstruction) obese mice.

C57bl/6J-Nr: C57bl/6J normal group (n=5) HFD-CTL: High Fat Diet-Negative Control (n=5)

UUO_HFD-CTL: High Fat Diet group with unilateral ureteral obstruction (n=5)

Fig. 5

Creatine level in serum of HFD-induced obese mice, and -renal cortex of each study group(UUO: unilateral ureteral obstruction) obese mice.

C57bl/6J-Nr: C57bl/6J normal group (n=5) HFD-CTL: High Fat Diet-Negative Control (n=5) UUO_HFD-CTL: High Fat Diet group with unilateral ureteral obstruction (n=5)

Fig. 6

Total Cholesterol level in serum of HFD-induced obese mice, and -renal cortex of each study group(UUO: unilateral ureteral obstruction) obese mice.

C57bl/6J-Nr: C57bl/6J normal group (n=5) HFD-CTL: High Fat Diet-Negative Control (n=5) UUO_HFD-CTL: High Fat Diet group with unilateral ureteral obstruction (n=5)

Fig. 7

HDL and LDL Cholesterol level in serum of HFD-induced obese mice, and -renal cortex of each study group(UUO: unilateral ureteral obstruction) obese mice.

C57bl/6J-Nr: C57bl/6J normal group (n=5) HFD-CTL: High Fat Diet-Negative Control (n=5) UUO_HFD-CTL: High Fat Diet group with unilateral ureteral obstruction (n=5)

Fig. 8

Triglyceride level in serum of HFD-induced

Fig. 9

Glucose level in serum of HFD-induced obese mice, and -renal cortex of each study group(UUO: unilateral ureteral obstruction) obese mice.

C57bl/6J-Nr: C57bl/6J normal group (n=5) HFD-CTL: High Fat Diet-Negative Control (n=5) UUO_HFD-CTL: High Fat Diet group with unilateral ureteral obstruction (n=5)

Fig. 10

Abdominal subcutaneous fat and Epididymal adipose tissue weight in HFD-induced obese mice, and -renal cortex of each study group(UUO: unilateral ureteral obstruction) obese mice.

C57bl/6J-Nr: C57bl/6J normal group (n=5) HFD-CTL: High Fat Diet-Negative Control (n=5) UUO_HFD-CTL: High Fat Diet group with unilateral ureteral obstruction (n=5)

Fig. 11

Liver weight in HFD-induced obese mice, and -renal cortex of each study group(UUO: unilateral ureteral obstruction) obese mice.

C57bl/6J-Nr: C57bl/6J normal group (n=5) HFD-CTL: High Fat Diet-Negative Control (n=5) UUO_HFD-CTL: High Fat Diet group with unilateral ureteral obstruction (n=5)

Fig. 12

mRNA expression of GLUT-9, IL-6, COX-2 were measured with Real Time-PCR analysis.

C57bl/6J: C57bl/6J normal group (n=5)

HFD-CTL: High Fat Diet-Negative Control (n=5)

UUO_HFD-CTL: High Fat Diet group with unilateral ureteral obstruction (n=5)

Table 1

Food Intake, Body Weight gain, Food Efficiency Ratio in HFD-Fed Obese Mice, and -Renal Cortex of Each Study Group(UUO: Unilateral Ureteral Obstruction) Obese Mice.

Group	Food intakes	Bodyweight gain	Food Efficiency

	(g/day)	(g/day)	(FER, %)
C57bl/6-Nr	3.46	0.191±0.01	5.53±0.31
HFD-CTD	2.89	0.377±0.03	13.05±0.92
UUO_HFD-CTD	5.97	0.280±0.03	4.70±1.29