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

Author(s)

Casquero, Andrea Camargo ^{[1, 2]} ; Berti, Jairo Augusto ^{[1, 3]} ; Sampaio Teixeira, Laura Lauand ^[1] ; Franco de Oliveira, Helena Coutinho ^[1]

Affiliation

^[1] Univ Estadual Campinas, Inst Biol, Dept Struct & Funct Biol, BR-13083862 Campinas, SP - Brazil

^[2] Ctr Univ Araraquara, BR-14801340 Araraquara, SP - Brazil

^[3] Univ Estadual Maringa, Dept Ciencias Morfofisiol, BR-87020900 Maringa, PR - Brazil

• Document type: Journal article
• Source: LIPIDS; v. 52, n. 12, p. 981-990, DEC 2017.
• Web of Science Citations: 3

Abstract

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. (AU)

• FAPESP's process: 11/50400-0 - Mitochondrial energy metabolism, redox state and functionality in cell death and cardiometabolic and neurodegenerative disorders
• Grantee: Aníbal Eugênio Vercesi
• Support Opportunities: Research Projects - Thematic Grants