Sexual Dimorphism in Human Lipid Metabolism

Abstract

The existing work demonstrates that striking differences exist between men and women in lipid kinetics. These differences cannot be explained simply by the presence and action of sex hormones and are not always due to secondary, phenotypic traits that characterize men and women (e.g., body-composition, regional fat distribution). In fact, some of these secondary traits may even be the result of sexual dimorphism in metabolism, and being of female or male genotype also determines intermediary metabolism. This review provides an overview of the currently available information regarding sexual dimorphism in human lipid metabolism but does not provide an in-depth account of current knowledge (due to limited space); it will be a broad introduction to those interested in the field and will, hopefully, stimulate further efforts to unravel the secrets of male and female metabolism. What has been discovered so far regarding differences in lipid metabolism between men and women is likely only the tip of the iceberg; clearly, more work is necessary to fully understand human substrate metabolism and the implications the presence of sexual dimorphism in the control of substrate kinetics has on the prevention and treatment of disease. J. Nutr. 135: 681-686, 2005.Within the past decade, a great deal of effort has been dedicated to uncovering the relevant physiologic differences between the sexes that may affect the prevention, diagnosis, and treatment of disease. For example, there are differences between the sexes in the lipid profile that may have clinical implications. In women, high plasma triglyceride (TG) 3 concentrations are independent and better predictors of cardiovascular disease risk than total or LDL cholesterol (1,2). Treatment of hypertriglyceridemia may, therefore, be of greater importance in women than in men. Also, differences in hepatic handling of fatty acids between men and women are likely responsible for the greater susceptibility of women to fatty liver disease and the more severe liver injury as a result of it (3). A better understanding of the control of lipid metabolism by a person's sex will therefore not only increase our knowledge of human intermediary and macronutrient metabolism, but may also be useful for the development of novel approaches for the treatment and prevention of disease.There are 2 general approaches when evaluating differences in metabolism between the sexes. One (clinically probably the most relevant) is to accept the differences in phenotype between men and women (e.g., body composition, regional fat distribution, aerobic fitness, all of which affect substrate metabolism in persons of the same sex) and acknowledge that the observed differences in lipid metabolism may be secondary to those characteristics. The other strives to eliminate as many potential confounding variables as practically feasible to determine whether sex per se represents an underlying factor in the control of metabolism.A simple view concerning the underlying cause for sexual dimorphism in metabolis...

Pathways Leading to Atherosclerosis

“…The relatively large effect of fat mass on ASP in 21 This induces higher levels of fatty acids, and consequently, the effect of FFA on TG might mask the relatively small direct effect of fat mass on TG in the female model. The sexual dimorphism in effects of serum lipid levels on cIMT is likely to be affected by sex hormones as well.…”

Sex-specific interaction between APOE genotype and carbohydrate intake affects plasma HDL-C levels: the Strong Heart Family Study

“…The issue of sex-specific variation as a factor in the response of plasma lipids to variation in dietary macronutrients appears consistently in many studies, however [16,40,58]. We hypothesize that a genetic predisposition and sexual dimorphism may explain some of the variation in response of HDL-C levels to dietary carbohydrate intake [47,51].…”

“…Kataoka et al [32] study examining the relationship of APOE polymorphisms to plasma lipids in the original Strong Heart Study individuals (n = 4,410), reported sexspecific variation associated with APOE polymorphisms. Genotype was not significantly associated with HDL-C variation in males (ages [45][46][47][48][49][50][51][52][53][54][55][56][57][58][59][60][61][62][63][64], however, in females, a significant trend for HDL-C levels was noted in all female subgroups studied: normal and diabetic, premenopausal and menopausal. HDL-C was higher in females carrying an e2 and lower in individuals carrying an e4 than for females with e3/3 genotypes.…”

“…The first might be explained through sexual dimorphism noted in lipid metabolism, with females showing a greater sensitivity to insulin's antilipolytic effects, and suppression of postprandial plasma fatty acid concentrations to compensate for their higher basal fatty acid flux [47]. The second issue may be connected to e4 as an effective ligand for triglyceride-rich lipoproteins (TRL), and high levels of APOE in HDL-C appearing to accelerate the lipoprotein's catabolism [29].…”

“…Our adjustment for body fat cannot account for variation in levels of adipokines [82] or the HDL scavenger receptor class B type I (SR-BI) which is highly expressed in adipose tissue [6]. Furthermore, sexual dimorphism has been widely documented in both adipose tissue levels and patterns, its hormones leptin and adiponectin [81,82], and energy homeostasis [79] all of which are influenced by nutritional status and affect energy balance, carbohydrate and lipid metabolism and insulin resistance [23,47].…”