Table 3.
Cell lines and animal models of lipotoxicity.
| Representative Model | Characteristics | Representative Treatments | Cardiac Phenotype Reported |
|---|---|---|---|
| Primary cardiomyocytes | Neonatal primary cardiomyocytes from one- to three-day-old wild type mice | Treated with palmitate for 24 h | Developed hypertrophy, inflammatory cytokines up-regulation, and oxidative stress [130] |
| AC16 cells | Human adult ventricular cardiomyocytes | Treated with palmitate for 16 h | Apoptosis [131] |
| HL-1 cells | Murine HL-1 cardiomyocytes | Treated with fatty acids for various time periods | Developed apoptosis and necrosis [132] |
| H9c2 cells | Cell line derived from an embryonic rat heart ventricle | Treated with palmitate for 24 h | Exhibited hypertrophy, up-regulation of inflammatory cytokines, and increased oxidative stress [130] |
| C57BL/6J mice | Susceptible to diet-induced obesity, T2D, and atherosclerosis. Deletion in nicotinamide nucleotide transhydrogenase (Nnt) exons 7–11 | Sixteen weeks with a high-fat/high-carbohydrate diet consisted of 60% kcal from fat food and drinking water with 42 g/L of carbohydrates (55% fructose and 45% sucrose) | Male mice exhibited systemic insulin resistance, myocardial steatosis with inflammatory foci, hypertrophy, and fibrosis [59] |
| CD1 mice | Albino mice | Eight weeks with a Western diet with 42% total fat, 12.8% saturated fat, and 30% sucrose | Male mice showed impaired cardiac systolic and diastolic function, myocardial inflammation, and fibrosis [133] |
| C57BL6J db/db mice | The db/db mouse has a point mutation in the leptin receptor gene. | Exhibited rapid weight gain when fed a regular chow diet, analyzed at 6 and 12 months of age | Female mice exhibited an increase in blood pressure, both male and female developed hyperglycemia, hypertrophic ventricular remodeling, and diastolic dysfunction with HFpEF, cardiomyocyte hypertrophy, and interstitial fibrosis [134] |
| Wistar rats | Its longevity and high rate of spontaneous tumors make it an ideal choice for aging studies. | Six weeks with HFD: 33.5% fat | Male rats showed cardiac hypertrophy; cardiac weight, cardiac fibrosis, and inflammatory markers were increased [135] |
| Sprague-Dawley rats | Albino rats | Forty-eight weeks with fructose and fat: 60 kcal/100 kcal saturated fat with 10% fructose | Male rats developed severe obesity, symptoms of metabolic syndrome, systemic insulin resistance, intramyocardial lipid accumulation, and cardiac hypertrophy [136] |
| ZDF rats | Rats develop obesity and insulin resistance at a young age | Maintained on RMH-B rat chow | Male rats showed an increase in cardiomyocyte size, LV performance, also developed perivascular fibrosis and cardiac hypertrophy [137] |
| ZSF1 rats | Two different leptin mutations (fa and facp) | They become hyperphagic and develop obesity. Analyzed at 26 weeks of age. | Female and male rats showed severe dyslipidemia without hyperglycemia, also displayed diastolic dysfunction, cardiac hypertrophy, and fibrosis [138] |
| Spontaneously hypertensive rats (SHRs) |
Hypertension starts to develop at five to six weeks of age | Twelve weeks with HFD: 60% fat, 20% carbohydrate, and 20% protein | Male rats showed hyperglycemia, dyslipidemia, showed a constellation of LV diastolic dysfunction, and myocardial fibrosis [139] |
| Hamsters | Normal Hamsters | Six weeks with HFD: Sucrose (162.58 g/kg), Soybean oil(162.58 g/kg), among others | Male hamsters developed cardiac fibrosis [140] |
| New Zealand White rabbits | Rabbits have a genetic deviation called albinism | Twelve weeks with standard rabbit chow with 10% added fat (6.7% corn oil and 3.3% lard) |
Female showed elevated LV weight, interstitial and perivascular collagen, fibrosis in coronary vessels, as well as accumulation of collagen in the cardiac interstitium [141] |
| Sheeps | Healthy obese Sheeps | Four months with high-energy soybean oil (2.2%), molasses, fortified grain, and maintenance hay | Sheeps exhibited increased LA volume, inflammatory infiltrates, and fibrosis [142] |
| Lee-Sung minipigs | Healthy obese minipigs | Six months with HFD (3786 Kcal/ kg, metabolic energy) |
Males and females showed augmented heart weight, interstitial and perivascular fibrosis, cardiac lipid accumulation and increased oxidative stress [143] |
| Bama miniature pigs | They have metabolic similarities to humans: lack of brown fat, and proportional organ sizes and cardiovascular systems | 23 months fed with a high-fat, high-sucrose diet (37% sucrose, 53% control diet, and 10% pork lard) | Pigs developed symptoms of metabolic syndrome and showed cardiac steatosis and hypertrophy. Insulin levels and heart weight were increased [127] |
| Mongrel dogs | Healthy dogs | Six weeks with a standard diet supplemented with 6 g/kg of rendered pork fat; 21,025 kJ/day (27% carbohydrate, 19% protein, and 53% fat) | Male dogs showed increased fasting insulin and markedly reduced insulin sensitivity, including a reduction in left ventricular function [144] |
AC16: cardiomyocyte cell line, HL-1: cardiac muscle cell line, H9C2: rat cardiomyoblast cell line, C57BL/6J: commonly called Black 6 mouse, T2D: type 2 diabetes, HFpEF: preserved ejection fraction, HFD: high-fat diet, ZDF: Zucker diabetic fatty, RMH-B: standard rat diet chow, LV: left ventricle.