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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

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.

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)
jkm-37-3-47f1.gif
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)
jkm-37-3-47f2.gif
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)
jkm-37-3-47f3.gif
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)
jkm-37-3-47f4.gif
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)
jkm-37-3-47f5.gif
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)
jkm-37-3-47f6.gif
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)
jkm-37-3-47f7.gif
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)
jkm-37-3-47f8.gif
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.
crossref

17. Fasshauer M, Paschke R. Regulation of adipocytokines and insulin resistance. Diabetologia. 2003; 46:12. 1594–1603.
crossref

18. Kim JY, Pham DD. Sasang Constitutional Medicine as a Holistic Tailored Medicine. Evidence-based Complementary and Alternative Medicine. 2009; 6:S1. 11–19.
crossref

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.
crossref

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.
crossref

27. White MF. Insulin signaling in health and disease. Science. 2003; 302:1710–1711.
crossref

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.
crossref

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.


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