Efeito do consumo da dieta ocidental sobre o metabolismo energético cardíaco em camundongos Swiss

Abstract

Obesity, a disease resulting from excessive accumulation of body fat, is a risk factor for type 2 diabetes, dyslipidemia and cardiovascular diseases, which are of high prevalence worldwide. Nutritional transition, a process associated with urbanization, has contributed to growing obesity, mainly by changing eating habits of the population, with broad inclusion of industrial products high in saturated fat, salt and sugar, called Western diet. The mechanisms by which diet-induced obesity leads to cardiovascular disease are not completely understood, but it is known that obesity leads to impairment of energy metabolism and cardiac function, increasing morbidity and mortality. In most obesity studies, the related cellular energy metabolism is compromised associated with mitochondrial dysfunction. In this context, it becomes important to investigate the effect of Western diet induced obesity in cardiac energy metabolism. In the present study, we evaluated the Western diet effect in Swiss mice for 1, 2, 6, 10 and 16 weeks from weaning. We analyzed biometric parameters, food intake, plasma biochemistry, glucose tolerance, mitochondrial oxygen consumption of cardiac fibers by carbohydrates (CHO) and fatty acids (AG) substrates, cardiac ATP content, the content of proteins involved in energy metabolism: CPT1, UCP2, PGC-1α, GLUT1, GLUT4, IRβ, PI3K, IRS-1, AMPK, pAMPK, FABPpm, CD36 and the mitochondrial complexes (I-V), in addition to the mRNA expression of proteins CPT1, UCP2, UCP3, GLUT4, PPAR-α and MHC-β, cardiac and liver histology. The differences between groups were analyzed by Two-way ANOVA, significance level p<0.05. Over 1 week the GO showed reduced CHO oxidation and RCR with increased CPT-1 mRNA. After 2 weeks we observed reduced AG oxidation and RCR, lower cardiac ATP content, IRS-1 and UCP2/UCP3 mRNA, increased fasting glucose, HOMA-IR, total cholesterol, CPT-1 and FABPpm contents. The GO fed for 6 weeks showed increased food intake (Kcal), epididymal fat, fasting glucose, HOMA-IR and the MHC-β mRNA. Reduced glucose tolerance, GLUT4 FM, IRS-1 and PI3K contents. 10 and 16 weeks of diet consumption caused increase in body mass, epididymal and retroperitoneal fat, liver weight and liver/body weight ratio, left ventricular weight and left ventricular weight/tibia length ratio, total cholesterol and triglycerides, glucose and fasted insulin, HOMA-IR and the MHC-β mRNA. Reduced oxidation and RCR of CHO and AG, cardiac ATP content, glucose tolerance, GLUT4 FM, IRS-1, PI3K and FABPpm contents, and PPAR-α, UCP2/UCP3 mRNA. Ectopic fat accumulation in the liver, disorganization and fibrosis of cardiomyocytes was observed in GO after 2 weeks. Increased pAMPK/AMPK ratio was demonstrated only with 10 weeks. Increased Lee index and lower content of PGC-1α, CD36 and GLUT4 mRNA, only after 16 weeks of diet. According to the results, we suggest that short-term Western diet consumption leads to cardiac energy metabolism impairment, resulting in the long-term the obesity establishment.