HDL biology
Exercise raises HDL in CETP-transgenic mice by lowering CETP activity 19%, and an anabolic steroid specifically blunts that effect (Lipids 2017)
Original title: 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 lipoprotein profiles, but human and animal studies have given conflicting results. This study used mice engineered to under-express the LDL receptor and express a human CETP transgene (CETP/R1), alongside R1-only controls, subjected to 6 weeks of swimming training with mesterolone supplementation in the final 3 weeks. Mesterolone raised LDL by 40% in sedentary CETP/R1 mice and cut HDL by 18% in exercised R1 mice. Independently, CETP expression lowered HDL by 21% and raised non-HDL by 15%; mesterolone raised VLDL by 42% regardless of other factors; and exercise training cut triglycerides by 25% and free fatty acids by 20%, raised LDL and HDL by 25 to 33%, and lowered CETP levels by 19%. Factor interactions showed the exercise-induced HDL rise was explained by exercise reducing CETP activity, and that mesterolone blunted this exercise-induced HDL increase. The authors present this as resolving a prior controversy over how exercise affects CETP, and demonstrating the capacity of mesterolone to counteract specific exercise benefits.
Original 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.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.