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

Article information

J Korean Med. 2016;37(3):47-61

Publication date (electronic) : 2016 September 30

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

Junghwan Park ¹, Yoonha Kim ¹, Jinyoung Kwak ¹, Seojin Hong ³, Jungmi Park ², Taekwon Ahn ¹^,

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 2016 June 01; Revised 2016 September 21; Accepted 2016 September 28.

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.

Table 2

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

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Article information Continued

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