A study on the effect on obesity and lipid metabolism in liver hypofunction animal-experimental model induced by  injection

Junghwan Park; Yoonha Kim; Jinyoung Kwak; Seojin Hong; Jungmi Park; Taekwon Ahn; Park, Junghwan; Kim, Yoonha; Kwak, Jinyoung; Hong, Seojin; Park, Jungmi; Ahn, Taekwon

doi:10.13048/jkm.16034

JKM > Volume 37(3); 2016 > Article

Park, Kim, Kwak, Hong, Park, and Ahn: A study on the effect on obesity and lipid metabolism in liver hypofunction animal-experimental model induced by Acetaminophen(AAP) injection

Original Article

The Journal of Korean Medicine 2016; 37(3): 47-61.

Published online: September 30, 2016

DOI: https://doi.org/10.13048/jkm.16034

A study on the effect on obesity and lipid metabolism in liver hypofunction animal-experimental model induced by Acetaminophen(AAP) injection

Junghwan Park¹, Yoonha Kim¹, Jinyoung Kwak¹, Seojin Hong³, Jungmi Park², Taekwon Ahn¹

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

²Daejeon Univercity

³Dep. of Acupuncture & Moxibustion Medicine, College of Korean Medicine, Daejeon Univ.

Correspondence to: 안택원 (Taekwon Ahn) 충청남도 천안시 서북구 노태산로 4 대전대학교 천안한방병원 사상체질과 Tel: +82-41-521-7535, Fax: +8241-521-7007, E-mail: twahn@dju.kr

Received June 01, 2016 Revised September 21, 2016 Accepted September 28, 2016

Abstract

Objectives

The objective of this research is to develop new animal-experimental model for Sasang Constitutional Medicine, especially for partial Taeyangin(one of four constitution which has good pulmonary function and poor hepatic function) by AAP intraperitoneal injection, and to estimate from the viewpoint of obesity and lipid metabolism.

Methods

The C57bl/6J mice was divided into 4 groups; Normal group, AAP group, High-Fat-Diet(HFD) group, and HFD+AAP group. 200mg AAP was injected intraperitoneally to the AAP group twice a week for six weeks, and HFD group was fed with 60%-High-fat Diet for six weeks. HFD+AAP group got both AAP injection and 60%-High-fat Diet at the same time for the same period. In this period, We measured the weight and Food Efficiency Ratio(FER, %) once a week. After six weeks, We conducted the blood chemical test from the groups, and extracted the fat tissue to measure weight.

Results & conclusion

In the liver function test, two AAP groups had higher AST and ALP, and normal LDH. The blood level of creatinine from all groups were normal. The rate in weight was lesser by 7.8% in HFD+AAP group, and had lesser FER than HFD group. Also They had lesser Total cholesterol and LDL cholesterol, and had more HDL cholesterol than HFD group. HFD+AAP group hadmore glucose in serum and lesser Insulin-like Growth Factor 1(IGF-1) than HFD group.

Keywords: Taeyangin, High-fat Diet, Obesity, Hyperlipidemia

Fig. 1

Body weight change in AAP & HFD-induced obese mice

➀ Normal group (n=10)

➁ APAP: AAP군, acetaminophen (200mg/kg i.p, 2times/week) (n=10)

➂ HFD-CTL: HFD-CTL군, 60%HFD control (n=10)

➃ HFD-APAP: HFD-AAP군, 60%HFD+AAP (200mg/kg i.p, 2times/week)(n=10)

Fig. 2

Food Efficiency Ratio (FER, %) of AAP & HFD–induced obese mice

➀ C57bl/6j-vehicle: Normal group (n=10)

➁ APAP 200mg/kg: AAP군, acetaminophen (200mg/kg i.p, 2times/week) (n=10)

➂ HFD-CTL: HFD-CTL군, 60%HFD control (n=10)

➃ HFD-APAP 200mg/kg: HFD-AAP군, 60%HFD+AAP (200mg/kg i.p, 2times/week)(n=10)

Fig. 3

AST, ALT, and ALP level in serum of AAP & HFD-induced obese mice.

➀ C57bl/6j-vehicle: Normal group (n=10)

➁ APAP 200mg/kg: AAP군, acetaminophen (200mg/kg i.p, 2times/week) (n=10)

➂ HFD-CTL: HFD-CTL군, 60%HFD control (n=10)

➃ HFD-APAP 200mg/kg: HFD-AAP군, 60%HFD+AAP (200mg/kg i.p, 2times/week)(n=10)

Fig. 4

Total cholesterol, triglyceride, LDL cholesterol, HDL cholesterol level in serum of AAP & HFD-induced obese mice

➀ C57bl/6j-vehicle: Normal group (n=10)

➁ APAP 200mg/kg: AAP군, acetaminophen (200mg/kg i.p, 2times/week) (n=10)

➂ HFD-CTL: HFD-CTL군, 60%HFD control (n=10)

➃ HFD-APAP 200mg/kg: HFD-AAP군, 60%HFD+AAP (200mg/kg i.p, 2times/week)(n=10)

Fig. 5

Glucose, NEFA, LDH level in serum of AAP & HFD-induced obese mice

➀ C57bl/6j-vehicle: Normal group (n=10)

➁ APAP 200mg/kg: AAP군, acetaminophen (200mg/kg i.p, 2times/week) (n=10)

➂ HFD-CTL: HFD-CTL군, 60%HFD control (n=10)

➃ HFD-APAP 200mg/kg: HFD-AAP군, 60%HFD+AAP (200mg/kg i.p, 2times/week)(n=10)

Fig. 6

Creatinine and uric acid level in serum of AAP & HFD-induced obese mice

➀ C57bl/6j-vehicle: Normal group (n=10)

➁ APAP 200mg/kg: AAP군, acetaminophen (200mg/kg i.p, 2times/week) (n=10)

➂ HFD-CTL: HFD-CTL군, 60%HFD control (n=10)

➃ HFD-APAP 200mg/kg: HFD-AAP군, 60%HFD+AAP (200mg/kg i.p, 2times/week)(n=10)

Fig. 7

Leptin and IGF-1 production level in serum of AAP & HFD-induced obese mice

➀ C57bl/6j-vehicle: Normal group (n=10)

➁ APAP 200mg/kg: AAP군, acetaminophen (200mg/kg i.p, 2times/week) (n=10)

➂ HFD-CTL: HFD-CTL군, 60%HFD control (n=10)

➃ HFD-APAP 200mg/kg: HFD-AAP군, 60%HFD+AAP (200mg/kg i.p, 2times/week)(n=10)

Fig. 8

Fat and organ weight in body of AAP & HFD-induced obese mice

➀ C57bl/6j-vehicle: Normal group (n=10)

➁ APAP 200mg/kg: AAP군, acetaminophen (200mg/kg i.p, 2times/week) (n=10)

➂ HFD-CTL: HFD-CTL군, 60%HFD control (n=10)

➃ HFD-APAP 200mg/kg: HFD-AAP군, 60%HFD+AAP (200mg/kg i.p, 2times/week)(n=10)

Table 1

Food Intake, Body Weight gain, and Food Efficiency Ratio of 60% High Fat diet Fed C57bl/6 Mice with AAP.

Group	Food intakes	Body weight gain	Food Efficiency Ratio
	(g/day)	(g/day)	(%)
ND	2.68	0.157±0.010	5.86±0.355
AAP	2.36	0.145±0.014	6.14±0.607
HFD-CTL	2.44	0.374±0.020	15.3±0.825
HFD+AAP	2.36	0.312±0.016	13.2±0.681

Table 2

Blood Biochemistry Prameters in AAP & HFD-fed Obese Mice.

	Normal	AAP	HFD-CTL	HFD+AAP
T-cholesterol (mg/dL)	112.2±4.9	130.2±4.1	204.9±7.8	189.7±5.7
HDL-cholesterol (mg/dL)	61.9±1.6	69.6±1.7	91.4±1.3	91.7±1.6
LDL-cholesterol (mg/dL)	12.2±0.6	14.6±0.3	19.0±1.3	17.2±0.4
Triglyceride (mg/dL)	99.6±11.4	94.2±6.7	159.2±23.2	95.7±6.0
LDH (U/L)	621.2±107.9	516.4±78.5	786.0±177.8	397.0±55.8
Glucose (mg/dL)	212.8±2.1	205.8±4.8	237.3±7.8	260.7±16.9
AST (U/L)	68.4±8.8	148.4±7.6	100.8±10.0	155.2±7.5
ALT (U/L)	36.3±3.7	59.9±12.7	39.6±4.1	69.9±15.5
ALP (U/L)	86.2±3.5	107.5±4.5	56.4±6.1	114.8±14.9
Uric acid (mg/dL)	4.0±0.8	2.8±0.2	4.3±0.7	3.1±0.2
Creatine (mg/dL)	0.4	0.4	0.3	0.4
NEFA (mEq/L)	1.3	1.6±0.1	1.7±0.1	1.4±0.1
IGF-1 (pg/ml)	9101.0±647.0	8427.0±571.0	9851.0±461.0	8142.8±422.0
Leptin (pg/ml)	4252.0±978.5	2843.9±285.5	61791.5±5548.8	47805.8±5956.2

참고문헌

1. The Korean Society for the Study of Obesity. Clinical Bariatrics. 2nd rev. Seoul. Koryouihak;(2001). p. 19-22. p. 34-52. p. 93-96. p. 97-106. p. 113-122. p. 124-131. p. 146-147. p. 157-162.

2. Korea Minister of Health & welfare. National Health & Nutrition Examination survey. (2013.

3. Keum, S, Jin, SH, & Keum, TH. A Study on etiological factors, symproms of a disease, and treatments of obesity based on dong-Yi Bo Gam. J of Korean Medicine, (1998). 19(2), 125-136.

4. Kim, DL, & Baek, TH. A Clinical study on the correlation of Sasang Constitution and Obesity. J of Sasang Constitutional medicine, (1996). 8(1), 319-335.

5. Bae, JH, & Shin, HD. A Clinical Study on the ratio of Sasang Constitution in Obesity patients. J of Korean Rehabilitation Medicine, (1997). 7(2), 141-151.

6. Choi, AR, Lee, SW, & Koo, DM. A Study on the Serum Lipid, Digestive Enzymes and Thyroid Hormone in Sasang Constitutional Medicine. J of Sasang Constitutional medicine, (2010). 22(2), 60-69.

7. Lee, KS, Seok, JH, Kim, SH, Kim, YH, Lee, SK, & Lee, EJ, et al. A Case-Control study on risk factors of obese patients of Each Sasang Constitution. J of Sasang Constitutional medicine, (2007). 19(4), 94-112.

8. Kim, EY, & Kim, JW. A Clinical study on the Sasang Constitution and Obesity. J of Sasang Constitutional medicine, (2004). 16(1), 100-111.

9. Shin, SW, & Lee, JH. A Study on the Characteristics of Ordinary Symptoms in Overweight and Obesity Patients according to Sasang Constitution. J of Korean medicine for obesity research, (2013). 13(1), 33-45.

10. Dept of Sasang Constitutional Medicine. All colleges of Korean med in Korea(compilation). The revised and enlarged Sasang Constitutional Medicine. Seoul. Jipmoondang;(2012). p. 272-273. p. 300-305. p. 721-723.

11. Lee MJ. A study on the anti-obese effect of Choweseuncheung-tang and Mahwangbalpyo-tang on High-fat diet obese mice. Doc of Kyunghee Univ;2011.

12. Kim, KY. A study on the effect of Taeeumin, Soeumin and Soyangin medicine on obese mice by Gold thioglucose. J of Sasang Constitutional medicine, (1996). 8(1), 295-318.

13. Cho, SW, & Park, SS. Effects of Taeyeumjowee-tang on Loss in Body Weight, Plasma Lipids and UCPI Revelation of Fated White Rats. J of Korean medicine, (2004). 24(2), 87-97.

14. Kim, KS, Lee, DU, Kim, YL, Hwang, MJ, Kim, GW, & Koo, BS. Anti-obesity and Anti-hyperlipidemic Effects of Taeyeumjowee-tang and its modified prescription. J of Oriental Neuropsychiatry, (2007). 18(2), 57-74.

15. Chen, PJ, Pang, VF, Jeng, YM, Chen, TJ, Hu, FC, & Chi, WT, et al. Establishment of a Standardized Animal Model of Chronic Hepatotoxicity Using Acetaminophen-Induced Hepatotoxicity in the Evaluation of Hepatoprotective Effects of Health Food. Journal of Food and Drug Analysis, (2012). 20(1), 41-47.

16. Park, KS. Relation between Adiponectin and Metabolic Risk Factors. Endocrinology and metabolism, (2005). 20(5), 441-443.

17. Fasshauer, M, & Paschke, R. Regulation of adipocytokines and insulin resistance. Diabetologia, (2003). 46(12), 1594-1603.

18. Kim, JY, & Pham, DD. Sasang Constitutional Medicine as a Holistic Tailored Medicine. Evidence-based Complementary and Alternative Medicine, (2009). 6(S1), 11-19.

19. Kim NY. Relationship between Leptin to Adiponectin Ratio and Metabolic Syndrome according to Sasang Constitution. Doc. of Sangji univ;(2011.

20. Kwak, CK, Lee, EJ, Song, IB, & Kim, KS. A case report of the ordinary symptoms on a Taeyangin constitution. J of Sasang Constitutional medicine, (2002). 14(3), 146-152.

21. Kim, KS, Lee, SY, Jung, SM, & Cha, JD. A case report of the interior disease of Taeyangin. J of Sasang Constitutional medicine, (2002). 14(3), 181-187.

22. Jang, ES, Do, JH, Jang, JS, Ku, BC, Yoo, JH, & Choi, HS, et al. The Characteristics of Taeyangin on Body Shape, Face, Voice and Temperament. J of Sasang Constitutional medicine, (2013). 25(3), 145-157.

23. Corcoran, GB, Mitchell, JR, Vaishnav, YN, & Horning, EC. Evidence that acetaminophen and N-hydroxyacetaminophen form a common arylating intermediate, N-acetyl-p-benzoquinoneimine. Mol Pharmacol, (1980). 18, 536-542.

24. Lee, EK, Kim, YJ, Kim, J, Lee, SJ, Kim, MS, & Kim, JG. Studies on the serum Lactic Dehydrogenase and LDH Isoenzymes in the Hepato-biliary Disease. The Korean Journal of Gastroenterology, (1982). 14(2), 67-74.

25. Nam, SM, Ha, EH, Seo, YJ, Park, HS, Jang, MH, & Seo, JH, et al. Effect of Obesity and Blood Lipid Profiles on Hyperlipidemia in Adults Aged Over 40 Years. The Korean Journal of Obesity, (2008). 17(1), 20-28.

26. Holland, WL, Brozinick, JT, Wang, LP, Hawkins, ED, & Sargent, KM, et al. Inhibition of ceramide synthesis ameliorates glucocorticoid, saturated fat and obesity-induced insulin resistance. Cell Metabolism, (2007). 5(3), 167-179.

27. White, MF. Insulin signaling in health and disease. Science, (2003). 302, 1710-1711.

28. Tran, TT, & Kahn, CR. Transplantation of adipose tissue and stem cells: role in metabolism and disease. Nature Reviews Endocrinology, (2010). 6(4), 195-213.

29. Kim, JH, & Song, JM. A Study on the Theory of JangBu(臟腑) in Sasang Constitutional Medicine. J of Sasang Constitutional Medicine, (2004). 16(1), 20-36.

30. Hwang MW. The lecture of Sasang constitution. 2nd Edition. Seoul. Koonja;(2013). p. 33-45.

31. Park SS. Donguisoosebowon sasangchobon-kwon. Seoul. Jipmoondang;(2002). p. 138-144.

32. Jeong, WY. Oriental Medical study on the Pathology of Gan(hepatic system). Journal of Korean Medicine, (1984). 5(1), 141-144.