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...

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Bibliographic Details
Published in:Lipids 2017-12, Vol.52 (12), p.981-990
Main Authors: Casquero, Andrea Camargo, Berti, Jairo Augusto, Teixeira, Laura Lauand Sampaio, de Oliveira, Helena Coutinho Franco
Format: Article
Language:English
Subjects:
Anabolic Agents - administration & dosage
Anabolic Agents - pharmacology
Animal models
Animals
Biomedical and Life Sciences
CETP
Cholesterol
Cholesterol Ester Transfer Proteins - blood
Cholesterol Ester Transfer Proteins - genetics
Cholesteryl ester transfer protein
Down-Regulation
Exercise
Fatty acids
Fitness training programs
Gene expression
Genetic modification
Health risks
High density lipoprotein
Humans
Life Sciences
Lipid metabolism
Lipidology
Lipoproteins
Lipoproteins (very low density)
Lipoproteins - blood
Lipoproteins - drug effects
Low density lipoprotein
Medical Biochemistry
Medicinal Chemistry
Mesterolone - administration & dosage
Mesterolone - pharmacology
Metabolic disorders
Metabolism
Mice
Mice, Transgenic
Microbial Genetics and Genomics
Models, Animal
Neurochemistry
Nutrition
Original Article
Physical training
Plasma levels
Receptors, LDL - genetics
Rodents
Sedentary Behavior
Steroid hormones
Steroids
Supplements
Swimming
Swimming - physiology
Testosterone
Training
Transgenic mice
Variance analysis
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Summary: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.
ISSN:0024-4201
1558-9307
DOI:10.1007/s11745-017-4299-1