Plasma concentrations of apolipoproteins C3 and C2 do not explain differences in insulin-stimulated endothelial-bound lipoprotein lipase activity in insulin resistant humans

Abstract

Elevated circulating triglycerides (i.e., dyslipidemia) is a hallmark of insulin resistance and is generally caused by decrease in lipoprotein lipase (LPL) activity. LPL hydrolyzes triglycerides (TG) into free fatty acids in plasma for use and/or storage in tissues (i.e., adipose, skeletal muscle). Plasma apolipoproteins (Apos) C3 and C2 interact with LPL to modulate its function by activating or inhibiting LPL. Previous research shows, in the metabolic environment of insulin resistance, the concentration of ApoC3 is increased in plasma while that of ApoC2 is decreased. Thus, Apos are considered key factors in regulating plasma lipid metabolism via modulation of LPL function. The purpose of this study was to investigate the concentrations of ApoC3 and ApoC2 in plasma and along endothelial-bound LPL activity in insulin resistant and healthy/non-insulin resistant individuals. We evaluated insulin resistance (IR)/insulin sensitivity (IS) using an oral glucose tolerance test (i.e., Matsuda index calculation) in subjects between ages 19 and 45 years old. Subjects were placed in the following two groups: 1) IR, if Matsuda index <4.0 (N=6; 4 males, 2 females; BMI: 23-45 kg/m2), or 2) IS, if Matsuda index >7.0 (N=11, 9 males, 2 females; BMI: 18-26 kg/m2). Subjects received an intravenous insulin infusion (0.5 mU/kg/min) for 30 minutes to resemble increased postprandial plasma insulin response. To release whole-body endothelial-bound LPL, subjects received an injection of intravenous heparin (75 UI/kg). Plasma samples were collected 10 minutes after the heparin infusion and analyzed for LPL concentration and activity, and ApoC3 and ApoC2 concentrations using ELISA. Differences between IS and IR subjects were determined using a t-test, and the P value was set at P < 0.05. Plasma LPL concentrations were not different between groups (IR = 457 ± 17 ng/ml, IS = 453 ± 27 ng/ml, P > 0.05), but plasma LPL activity was higher in the IR subjects (IR = 665 ± 113 nmol/min/ml, IS = 365 ± 59 nmol/min/ml, P = 0.02). IR subjects had higher concentrations of plasma ApoC3 (IR = 3.6 ± 0.5 mg/dl, IS = 2.7 ± 0.2 mg/dl, P=0.03) but ApoC2 was not different between groups (IR = 0.15 ± 0.03 mg/dl, IS = 0.11 ± 0.01 mg/dl, P = 0.11). The ratio of circulating LPL to circulating ApoC3 (IR = 145 ± 22, IS = 176 ± 15) or circulating ApocC2 (IR = 4104 ± 844, IS = 4391 ± 483) were not different between groups (P > 0.05). We conclude that interactions of LPL with APOC3 and ApoC2 may not be main determinants regulating differential whole-body plasma LPL activity under plasma insulin-stimulated conditions in insulin resistant humans. American Diabetes Association Grant #7-12-CT-40 This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.