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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

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