Establishment of a New Hyperglycemic Obesity Cardiac Dysfunction Mouse Model with Triacsin C

doi:10.12300/j.issn.1674-5817.2024.078

Abstract

Abstract:

Objective This study aims to establish a novel hyperglycemic obesity mouse model by utilizing Triacsin C, an inhibitor of acyl-CoA synthetase long-chain family member 1 (ACSL1), combined with a high-fat diet, to simulate the changes in adipose tissue and cardiac function observed in patients with obesity-related type 2 diabetes. Methods Twenty adult SPF-grade male C57BL/6J mice were randomly divided into two groups: the Control group (injected intraperitoneally with citric acid-sodium citrate buffer, Con group) and the TC group (injected intraperitoneally with Triacsin C, TC group). After four consecutive weeks of intraperitoneal injections, both groups were fed high-fat diets. Body weight and glucose tolerance of the mice were assessed every eight weeks. The models were considered successful if fasting blood glucose exceeded 8 mmol/L or blood glucose was above 15 mmol/L two hours after glucose injection. Cardiac function, including ventricular end-diastolic diameter (LVEDD), left ventricular end systolic diameter (LVESD), end-diastolic interventricular septal thickness (EDIVS), left ventricular ejection fraction (LVEF), and left ventricular short-axis fractional shortening (FS), was measured by echocardiography. HE staining was used to detect the changes in epididymal white adipose tissue (WAT) and brown adipose tissue (BAT). Immunofluorescence technology was used to analyze changes in CD31 and UCP1 in BAT. ACSL1 expression in myocardial tissue was tested by Western blotting. Results The fasting blood glucose levels were (8.14±1.43) mmol/L in the Con group and (8.18±0.85) mmol/L in the TC group (P>0.05) , and the 2-hour postprandial blood glucose levels were (19.8±4.01) mmol/L in the Con group and (22.60±3.97) mmol/L in the TC group (P<0.05). This indicated that both groups of diabetic mouse models were successfully established. Compared to the Con group, the TC group showed poor glucose tolerance; significant decreases in LVEDD, LVEF and FS (P<0.05); significant increases in WAT and BAT areas (P<0.05); significant decreases in CD31 and UCP1 expression (P<0.05); and a significant decrease in the expression of ACSL1 in myocardial tissues (P<0.05). Conclusion Compared with the high-fat diet-induced type 2 diabetes model, the new hyperglycemic obesity and cardiac dysfunction mouse model, created by the combination of Triacsin C and a high-fat diet, is feasible and allows for easier observation of brown adipose tissue whitening, insulin resistance and cardiac dysfunction.

Key words: Animal model, Acyl-CoA synthetase long-chain family member 1, Brown adipose tissue, Cardiac dysfunction, Mice

CLC Number:

R-332

ZHAO Xiaona,WANG Peng,YE Maoqing,et al. Establishment of a New Hyperglycemic Obesity Cardiac Dysfunction Mouse Model with Triacsin C[J]. Laboratory Animal and Comparative Medicine, 2024, 44(6): 605-612. DOI: 10.12300/j.issn.1674-5817.2024.078.

Figures/Tables 5

Figure 1 Changes in mouse weight and glucose tolerance after high-fat dietNote：Con is the control group；TC is the experimental group， i.e.， the Triacsin C intraperitoneal injection group. A， Changes in body weight of the Con and TC groups at 0， 8，and 16 weeks of high-fat diet （n=6）； B-C， Changes in the glucose tolerance of the Con and TC groups at 8 weeks （B） and 16 weeks （C） of high-fat diet， respectively （n=6）. Compared to the control group，*P<0.05，**P<0.01.

Figure 2 Changes in ACSL1 expression in cardiac tissues of the different group of miceNote： Con is the control group； TC is the experimental group， i.e. the Triacsin C intraperitoneal injection group. A， Western blotting image of ACSL1 in cardiac tissue； B， Quantitative analysis of ACSL1 in cardiac tissue （n=6）. Compared to the control group， *P<0.05.

Table 1 Indexes of cardiac function in each group of mice measured by echocardiography

参数 Parameters	对照组 Con group	实验组 TC group
LVEDD/mm	3.59±0.12	3.06±0.36*
LVESD/mm	2.25±0.26	2.47±0.71
EDIVS/mm	0.93±0.15	1.02±0.14
LVEF/%	70.87±8.71	54.79±10.27*
FS/%	42.71±2.89	34.26±5.96*
E/A	1.32±0.20	1.62±0.36

Figure 3 Pathological changes in adipose tissues in each group of mice after 16 weeks of high-fat dietNote：Con is the control group； TC is the experimental group， i.e. the Triacsin C intraperitoneal injection group. A-B， HE staining of epididymal white adipose tissue （WAT） after 16 weeks of high-fat diet （n=6， ×100）； C， Area of epididymal WAT of mice after 16 weeks of high-fat diet； D-E， HE staining of BAT after 16 weeks of high-fat diet （n=6， ×100）； F， Area of BAT after 16 weeks of high-fat diet. Scale bar is 200 μm. Compared to the control group， *P<0.05.

Figure 4 Expression of CD31 and UCP1 in brown adipose tissues of different groups of miceNote： Con is the control group； TC is the experimental group， i.e.， the Triacsin C intraperitoneal injection group. A， Staining of brown adipose tissue marker UCP1 （green， n=6， ×200）， and vascular endothelial cell marker CD31 （red， n=6， ×200）， with the cell nucleus stained blue （Scale bar is 100 μm）； B， Analysis of CD31 and UCP1 marked area. Compared with the control group， *P<0.05.

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