Abstract
Reduced white adipose tissue (WAT) LPL activity delays plasma clearance of TG-rich lipoproteins (TRLs). We reported the secretion of apoC-I, an LPL inhibitor, from WAT ex vivo in women. Therefore we hypothesized that WAT-secreted apoC-I associates with reduced WAT LPL activity and TRL clearance. WAT apoC-I secretion averaged 86.9 ± 31.4 pmol/g/4 h and 74.1 ± 36.6 pmol/g/4 h in 28 women and 11 men with BMI ≥27 kg/m(2), respectively, with no sex differences. Following the ingestion of a (13)C-triolein-labeled high-fat meal, subjects with high WAT apoC-I secretion (above median) had delayed postprandial plasma clearance of dietary TRLs, assessed from plasma (13)C-triolein-labeled TGs and apoB48. They also had reduced hydrolysis and storage of synthetic (3)H-triolein-labeled ((3)H)-TRLs in WAT ex vivo (i.e., in situ LPL activity). Adjusting for WAT in situ LPL activity eliminated group differences in chylomicron clearance; while adjusting for plasma apoC-I, (3)H-NEFA uptake by WAT, or body composition did not. apoC-I inhibited in situ LPL activity in adipocytes in both a concentration- and time-dependent manner. There was no change in postprandial WAT apoC-I secretion. WAT apoC-I secretion may inhibit WAT LPL activity and promote delayed chylomicron clearance in overweight and obese subjects. We propose that reducing WAT apoC-I secretion ameliorates postprandial TRL clearance in humans.
Highlights
Reduced white adipose tissue (WAT) LPL activity delays plasma clearance of TG-rich lipoproteins (TRLs)
The cardiometabolic risk associated with reduced HDL cholesterol (HDL-C) and/or elevated LDL cholesterol (LDL-C) has been well-established, the cardiometabolic risk associated with elevated TG-rich lipoproteins (TRLs) has not
There were no associations between several markers of adiposity with total apoC-I, WAT apoC-I, postprandial fat clearance, WAT in situ LPL activity (WAT 3H-lipids and medium 3H-trioleinlabeled NEFA (3H-NEFA) generated from the hydrolysis of 3H-triolein-labeled TG-rich lipoproteins (3H-TRL) substrate), or 3H-NEFA uptake
Summary
Reduced white adipose tissue (WAT) LPL activity delays plasma clearance of TG-rich lipoproteins (TRLs). Following the ingestion of a 13C-trioleinlabeled high-fat meal, subjects with high WAT apoC-I secretion (above median) had delayed postprandial plasma clearance of dietary TRLs, assessed from plasma 13C-trioleinlabeled TGs and apoB48. They had reduced hydrolysis and storage of synthetic 3H-triolein-labeled (3H)-TRLs in WAT ex vivo (i.e., in situ LPL activity). Dysfunctional WAT has reduced metabolic flexibility and is unable to switch promptly from fasting (catabolic) to postprandial (anabolic) state This leads to delayed TRL clearance, impaired remodeling of circulating lipoproteins, and increased TRL flux to peripheral tissues; thereby increasing cardiometabolic risks [11, 12]. The underlying mechanisms promoting WAT dysfunction and delayed TRL clearance are not fully understood
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
