Sex- and endurance training-mediated cardiovascular protection through lipids during exercise

Abstract

Premenopausal women and endurance-trained individuals of either sex have reduced cardiovascular disease (CVD) risk. Endurance training shifts fuel selection towards fats to spare carbohydrates; interestingly, women prioritize fats as an energy resource more than men do during exercise. Relying on fats during exercise drives whole-body lipolysis and promotes lipid uptake and oxidation capacity in skeletal muscles. These metabolic adaptations during exercise result in protection against diet-induced obesity, a healthy body fat distribution, and reduced plasma triacylglycerol (TG) concentrations. Here, we analyze how sex differences and endurance training mediate changes in skeletal muscles, including exercise-induced lipolysis, lipid uptake and β-oxidation, intramuscular TG storage, and postexercise lipid metabolism, and discuss how regulating this processes affects CVD risk.

Keywords: CVD risk; endurance training; intramyocellular triacylglycerol (IMTG); muscle fiber types; post-exercise recovery; sex differences in fuel selection.

Figure 1.. Fatty acid oxidation (FAO) rates are higher in females than males and higher in endurance-trained individuals than untrained counterparts.

A. FAO rates for healthy sedentary people maximize at 45–65% of V̇O₂max, and females exhibit higher FAO rates than males. B. FAO rates are increased in endurance-trained individuals compared to untrained people in A; the sex difference in FAO rates is diminished in endurance-trained individuals. FFM: fat-free mass.

Figure 2.. Regulatory enzymes in lipid uptake, transportation, hydrolysis, and oxidation in skeletal muscles during exercise.

Enzymes that are increased in females are in dark red, such as peroxisome proliferate-activated receptors α and γ (PPARα/γ), Acyl-CoA dehydrogenase (ACAD), trifunctional protein (TFP), and citrate synthase (CS). Enzymes that are increased in females and endurance-trained individuals are shown in blue, such as lipoprotein lipase (LPL), CD36, hormone-sensitive lipase (HSL), and PPARγ-coactivator-1α (PGC1α). ACS: acyl-CoA synthase; ANP: atrial natriuretic peptides; ATGL: adipose triacylglycerol lipase; CPT1: carnitine palmitoyl transferase 1; CACT: carnitine acyl-CoA translocase; FABPpm: plasma membrane fatty acid binding protein; TRL: triacylglycerol-rich lipoprotein. Figure created using BioRender.