In vivo triglyceride synthesis in subcutaneous adipose tissue of humans correlates with plasma HDL parameters

Abstract

a b s t r a c tBackgrounds and aims: Low concentrations of plasma HDL-C are associated with the development of atherosclerotic cardiovascular diseases and type 2 diabetes. Here we aimed to explore the relationship between the in vivo fractional synthesis of triglycerides (f TG ) in subcutaneous (s.q.) abdominal adipose tissue (AT), HDL-C concentrations and HDL particle size composition in non-diabetic humans. Conclusions: Our study demonstrated an in vivo association between subcutaneous abdominal adipose tissue lipid dynamics and HDL parameters in humans, but this was true for women not men. Positive association with L-HDL and negative with I-HDL suggest that subcutaneous abdominal adipose tissue lipid dynamics may play an important role in production of mature functional HDL particles. Further studies evaluating the mechanism responsible for these associations and the observed gender differences are important and warranted to identify potential novel targets of intervention to increase the production of atheroprotective subclasses of HDL-Cs and thus decreasing the risks of development of atherosclerotic conditions.

Sex‐dependent difference in the relationship between adipose‐tissue cholesterol efflux and estradiol concentrations in young healthy humans

“…The current results from our pilot study demonstrate that the estradiol levels in serum are significantly associated with subcutaneous abdominal AT cholesterol efflux. Although, we have studied a small number of men and women, the current data in conjunction with our previous work (Tuvdendorj et al, 2016) strongly suggests that this association is sex‐dependent. The role of AT in preventing the development of T2D, and atherosclerotic CVD in humans is well accepted (Tuvdendorj et al, 2013; Iqbal et al, 2017); however, the mechanisms underlying the sex‐dependent variabilities are not well understood.…”

“…Male patients with dementia have lower HDL‐C and higher TC levels than females (Ancelin et al, 2013; Ancelin et al, 2014; Hazzard and Applebaum‐Bowden, 1990), and men are known to have a higher occurrence of vascular dementia and subsequent cognitive decline. However, our current and previously published (Tuvdendorj et al, 2016) data suggest that if estrogen is the main determinant of AT health in women, this is likely not the case for men (Fig. 1C).…”

“…Our group and others have demonstrated that HDL‐C metabolism is strongly associated with adipose tissue (AT) health (Chung et al, 2011; Le Lay et al, 2003; Verghese et al, 2007; Zhang et al, 2010; Tuvdendorj et al, 2016). We have also demonstrated that in humans this association is sex‐dependent (Tuvdendorj et al, 2016). Therefore, here we aimed to determine if AT lipid kinetics, estimated as subcutaneous abdominal AT cholesterol efflux, associates with serum concentration of sex hormone estradiol, which is one of the active forms of estrogen.…”

Racial differences in in vivo adipose lipid kinetics in humans

“…Previous analyses demonstrated that f TG was associated with facets of the metabolic syndrome, including insulin resistance and lipid profile measures (10,39). Notably, our study included only women who were metabolically healthy.…”

Current and future therapies for addressing the effects of inflammation on HDL cholesterol metabolism

“…Our results demonstrated that f TG is inversely associated with the markers of insulin sensitivity (Tuvdendorj et al ., ). Furthermore, f TG is associated with the total concentration of HDL‐C and the fractional contribution of large HDL‐C particles (Tuvdendorj et al ., ). Based on the principles of the stable isotope tracer labelling approach (synthesis‐breakdown/lipolysis = net balance; Turner et al ., ; Wolfe and Chinkes, ; Tuvdendorj et al ., , ) and the reports that AT TG efflux directly correlates with the efflux of cholesterol (Le Lay et al ., ; Verghese et al, ), we assumed that the f TG represented AT cholesterol efflux in these individuals.…”