Human apoCIII transgenic mice with epicardial adipose tissue inflammation and PRESERVATION of the cardiac plexus.

Hypertriglyceridemia is a result of the increase in the serum levels of lipoproteins, which are responsible for the transport of triglycerides and can be caused by genetic and/or metabolic factors. Animal models which either express or lack genes related to changes in the lipoproteins profile are useful to understand lipid metabolism. Apolipoprotein CIII (apoCIII) is an important modulator of hepatic production and peripheral removal of triglycerides. Mice that overexpress the apoCIII gene become hypertriglyceridemic, showing high concentrations of free fatty acids in the blood. Since hypertriglyceridemia is related to atherosclerosis, and the latter refers to cardiac alterations, this study aimed at evaluating the morphological, morphometric and quantitative profiles of the cardiac plexus, as well as the morphometric and histopathological aspects of the epicardial adipose tissue in human apoCIII transgenic mice. Therefore, 8-12-month-old male C57BL/6 mice that overexpressed human apoCIII (CIII) and their respective controls were used. Our results showed that overexpression of human apoCIII did not modify morphological or quantitative parameters of cardiac plexus neurons; however, age increased both, the area and the number of such cells. Furthermore, there was a direct correlation of this dyslipidemia to the thickening of periganglionar type 1 collagens. On the other hand, this overexpression caused epicardial adipose tissue inflammation and an increase in the area of the adipocytes, thus, favoring the recruitment of inflammatory cells in this tissue. In conclusion, this overexpression is harmful since it is related to an increase in cardiac adiposity, as well as to a predisposition to an inflammatory environment in the epicardial fat and to the incidence of cardiovascular diseases.

Chronic Exercise Reduces CETP and Mesterolone Treatment Counteracts Exercise Benefits on Plasma Lipoproteins Profile: Studies in Transgenic Mice.

Regular exercise and anabolic androgenic steroids have opposing effects on the plasma lipoprotein profile and risk of cardio-metabolic diseases in humans. Studies in humans and animal models show conflicting results. Here, we used a mice model genetically modified to mimic human lipoprotein profile and metabolism. They under-express the endogenous LDL receptor gene (R1) and express a human transgene encoding the cholesteryl ester transfer protein (CETP), normally absent in mice. The present study was designed to evaluate the independent and interactive effects of testosterone supplementation, exercise training and CETP expression on the plasma lipoprotein profile and CETP activity. CETP/R1 and R1 mice were submitted to a 6-week swimming training and mesterolone (MEST) supplementation in the last 3 weeks. MEST treatment increased markedly LDL levels (40%) in sedentary CETP/R1 mice and reduced HDL levels in exercised R1 mice (18%). A multifactorial ANOVA revealed the independent effects of each factor, as follows. CETP expression reduced HDL (21%) and increased non-HDL (15%) fractions. MEST treatment increased the VLDL concentrations (42%) regardless of other interventions. Exercise training reduced triacylglycerol (25%) and free fatty acids (20%), increased both LDL and HDL (25-33%), and reduced CETP (19%) plasma levels. Significant factor interactions showed that the increase in HDL induced by exercise is explained by reducing CETP activity and that MEST blunted the exercise-induced elevation of HDL-cholesterol. These results reinforce the positive metabolic effects of exercise, resolved a controversy about CETP response to exercise and evidenced MEST potency to counteract specific exercise benefits.