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Journal of Peking University (Health Sciences) ›› 2020, Vol. 52 ›› Issue (3): 557-563. doi: 10.19723/j.issn.1671-167X.2020.03.024

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Establishment of high-fat diet-induced obesity and insulin resistance model in rats

Xiao-yuan ZHANG,Cheng-cheng GUO,Ying-xiang YU,Lan XIE,Cui-qing CHANG()   

  1. Institute of Sports Medicine, Peking University Third Hospital, Beijing 100191, China
  • Received:2018-05-17 Online:2020-06-18 Published:2020-06-30
  • Contact: Cui-qing CHANG E-mail:changcuiqing@126.com
  • Supported by:
    National Key Research and Development Program(2016YFD0400603)

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Abstract:

Objective: To investigate the appropriate conditions and duration for establishing a high-fat diet-induced obesity and insulin resistance model in rats.Methods: Forty-five 6-week-old male Sprague-Dawley (SD) rats were randomly assigned into 2 groups: (1) control group (CON), (2) high-fat diet group (HFD). HFD was fed with a high-fat diet (45% kcal from fat) while CON with chow diet. After four-weeks of high-fat diet feeding, the rats of obesity resistance (OR) were eliminated according to body weight sorting, whereas obese (OB) rats were continued feeding a high-fat diet until 12 weeks. Body weight and food intake were recorded weekly. Glucose tolerance was evaluated by oral glucose tolerance test (OGTT) in 4 weeks, 8 weeks and 12 weeks. At the end of 12 weeks, insulin releasing test and visceral fat mass were measured and HE staining of the liver, adipose tissue and pancreatic tissue were conducted.Results: After 4 weeks of a high-fat diet, the body weight of HFD was 17.8% higher than that of CON (P=0.001), and the rate of obesity was 67.6%-78.4%. Glucose tolerance of OB rats was impaired with a higher blood glucose concentration at 120 min (P<0.001) and a higher area under the curve (AUC, P=0.037) in OGTT compared with CON. The rate of obesity and insulin-resistance rats was 79.3%. After 8 weeks of feeding, the body weight in OB was 30.4% higher than CON (P<0.001). In OGTT, blood glucose levels at 60 min and 120 min were 35.6% and 36.4% higher than those in CON (both P<0.001), and AUC was 21.7% (P<0.001) higher than that of CON. The rate of obesity and insulin-resistance rats was 100.0%. After 12 weeks of feeding, the body weight in OB was 36.9% higher than that in CON (P<0.001). In OGTT, the blood glucose levels at 60 min and 120 min were 24.8% (P=0.001) and 34.6% (P<0.001) higher than those in CON, and AUC was 16.1% (P=0.019) higher than that of CON. The rate of obesity and insulin-resistance rats was 93.3%. The insulin releasing test showed that serum insulin concentration at each time point (0, 30, 60, 120 min) was higher than that in CON, with a 6.3-times higher than that in CON at 120 min (P=0.008). Pathological changes were observed in islets and liver in the OB rats.Conclusion: After 4 weeks of a high-fat diet (45% kcal from fat) feeding in six-weeks SD rats, the rats of OR were eliminated. Impaired glucose tolerance was found in OB rats after 4 weeks of feeding, and the rate was higher after 8-12 weeks of high-fat diet feeding.

Key words: Insulin resistance, Obesity, Diet, high-fat, Models, animal

CLC Number: 

  • R-332

Figure 1

Changes in body weight of rats *P<0.05, **P<0.01, OB compared with CON. Only week 1 to week 4 of OR is shown. CON, control; OB, obesity; OR, obesity resis-tance."

Figure 2

OGTT of rats with high-fat diet feeding *P<0.05, OB compared with CON. CON, control; OB, obesity; OR, obesity resistance; OGTT, oral glucose tolerance test; AUC, area under the curve; W4, week 4; W8, week 8; W12, week 12."

Figure 3

Insulin releasing test with high-fat diet feeding for 12 weeks in rats *P<0.05, OB compared with CON. CON, control; OB, obesity."

Table 1

The pathological changes of high-fat diet on adipose tissue, liver and islets in SD rats [median (P25, P75)]"

Items CON (n=8) OB (n=8)
Adipocyte area/μm2 8 282.6 (6 610.8, 8 715.9) 14 509.4 (12 534.4, 14 892.9)*
Degree of inflammatory infiltration of adipocyte 0.0 (0.0, 0.8) 2.0 (1.0, 2.0)**
Degree of hepatocyte steatosis 0.0 (0.0, 0.0) 1.0 (0.0, 2.8)*
Islet area/μm2 17 202.7 (5 302.5, 38 872.1) 151 020.5 (17 262.6, 431 886.1)*
Number of islets in ten fields of 10×vision 14.0 (12.3, 17.5) 18.0 (14.8, 23.8)

Figure 4

Pathological section and hematoxylin and eosin stain Arrow in B, infiltration of foam cells in adipocytes; Arrow in D, hepatocyte steatosis; Arrow in F, hyperplasia of pancreatic islet with irregular shape. CON, control; OB, obesity."

Table 2

The effect of high-fat diet on Lee’s index and organ weight"

Group n Body weight/g Visceral fat
weight/g		 Percentage
of visceral fat		 Lee’s index Liver weight/g Liver index Kidney weight/g Kidney index
CON 8 498.88±29.28 16.70±5.65 3.32%±0.97% 26.93±0.50 14.63±1.20 2.94±0.27 3.16±0.29 0.63±0.04
OB 8 680.86±64.19* 61.46±17.66* 8.90%±1.72%* 29.20±0.71* 16.07±1.02* 2.37±0.20* 3.41±0.15 0.50±0.04*
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