White Adipose Tissue Apolipoprotein C-I Secretion in Relation to Delayed Plasma Clearance of Dietary Fat in Humans

Abstract

Objective-White adipose tissue (WAT) dysfunction is characterized by delayed clearance of dietary triglyceride-rich lipoproteins (TRL). We reported that apolipoprotein (apo) C-I, a transferable apolipoprotein that inhibits lipoprotein lipase activity when bound to TRL, was produced by a human adipocyte model. Thus, we aimed to determine whether increased WAT apoC-I secretion is related to delayed dietary fat clearance in humans. Methods and Results-After the ingestion of a 13 C-triolein-labeled high-fat meal, postmenopausal obese women with highfasting WAT apoC-I secretion (median >0.81 μmol/L per g/4 hours, n=9) had delayed postprandial plasma clearance of 13 C-triglyceride and 13 C-nonesterified fatty acids over 6 hours compared with controls. WAT apoC-I secretion over 4 hours correlated with fasting total and non-high-density lipoprotein apoC-I but not with high-density lipoprotein apoC-I and was the primary predictor of 4-hour postprandial increases in TRL apoC-I. Correction for TRL apoC-I eliminated the association of WAT apoC-I with 6-hour area under the curve of plasma 13 C-triglyceride; correction for insulin sensitivity or inflammation did not. Finally, in addition to apoC-I, WAT secreted considerable amount of apoC-II, apoC-III, and apoE over 24 hours; however, only WAT apoC-I secretion was associated with 6-hour area under the curve of plasma 13 C-triglyceride. Conclusion-Increased

WAT apoC-I secretion: role in delayed chylomicron clearance in vivo and ex vivo in WAT in obese subjects

“…Body composition was measured by dual energy X-ray absorptiometry (General Electric Lunar Corp., version 6.10.019), plasma glucose by an automated analyzer (YSI 2300 Stat Plus), serum insulin and C-peptide by radioimmunoassay kits (Millipore Corp.), plasma lipids and apoB by an automated analyzer COBAS Integra 400 (Roche Diagnostics), plasma chylomicron concentration by an ELISA kit against human apoB48 (Biovendor), and plasma apoC-I by an in-house ELISA, as previously reported (14,31). Homeostatic model assessment of insulin resistance (HOMA-IR) was calculated according to Matthews et al (32).…”

“…Homeostatic model assessment of insulin resistance (HOMA-IR) was calculated according to Matthews et al (32). Lipoprotein cholesterol content and LDL diameter were measured by a polyacrylamide gel electrophoresis system (FDA-approved, Lipoprint system; Quantimetrix) (14,29).…”

“…Postprandial dietary fat metabolism was assessed as previously reported (14,29). In brief, subjects consumed a high-fat meal labeled with 13 C-triolein [glycerol tri(oleate-1- C-NEFA were measured over 0, 1, 2, 4, and 6 h using isotope ratio mass spectrometry (14,29).…”

“…In brief, subjects consumed a high-fat meal labeled with 13 C-triolein [glycerol tri(oleate-1- C-NEFA were measured over 0, 1, 2, 4, and 6 h using isotope ratio mass spectrometry (14,29). The postprandial clearance rates of plasma total TG, 13 C-TG, and 13 C-NEFA were calculated as the area under the 6 h curve of the incremental increase above baseline levels of plasma lipids (iAUC 6hrs ).…”

“…Subjects' fasting WAT samples were collected by needle biopsy from the right hip (gynoid) area under local anesthesia (Xylocaine, 20 mg/ml; AstraZeneca) as previously described (14,29). WAT samples were cleaned and preincubated in 1 ml HBSS for 30 min to wash out products of cellular damage induced by the biopsy.…”