title: Dietary modulation of plasma angiopoietin-like protein 4 concentrations in healthy volunteers and in patients with type 2 diabetes.
abstract: BACKGROUND
  Angiopoietin-like protein 4 (ANGPTL4) has been identified as an inhibitor of lipoprotein lipase. Preliminary data suggest that plasma nonesterified fatty acids (NEFAs) raise plasma ANGPTL4 concentrations in humans.
  
  
  OBJECTIVE
  The objective was to assess plasma ANGPTL4 concentrations after various nutritional interventions that increase NEFA concentrations in healthy subjects and in patients with type 2 diabetes mellitus.
  
  
  METHODS
  We studied 4 groups, both at baseline and after 3 d of either fasting (n = 22 healthy men), a very-low-calorie diet (VLCD; n = 10 healthy men and n = 10 patients with diabetes), or a high-fat, high-energy diet (HFED; n = 15 healthy men). Plasma ANGPTL4, NEFA, and triglyceride concentrations were measured.
  
  
  RESULTS
  In healthy men, a VLCD increased ANGPTL4 from 13.2 (IQR: 8.1-24.2) at baseline to 18.2 (16.7-33.4) ng/mL (P < 0.05), fasting increased ANGPTL4 from 10.6 (7.6-17.6) to 28.0 (23.1-35.0) ng/mL (P < 0.05), and an HFED increased ANGPTL4 from 13.9 (8.2-22.0) to 17.2 (11.2-23.6) ng/mL (P < 0.05). In men with diabetes, a VLCD also increased ANGPTL4, from 10.9 ± 2.4 to 19.2 ± 3.2 ng/mL (P < 0.05). All interventions significantly increased plasma NEFAs in both healthy men and patients with diabetes. The change in ANGPTL4 positively correlated with the change in NEFA concentrations (β = 0.048, P < 0.001) and negatively correlated with the change in plasma triglycerides (β = -0.051, P = 0.01).
  
  
  CONCLUSIONS
  Three days of either fasting, a VLCD, or an HFED increased plasma ANGPTL4 concentrations in healthy men, concomitantly with increased plasma NEFA concentrations. Similarly, a VLCD in patients with diabetes increased ANGPTL4 concentrations, concomitantly with increased NEFA concentrations.
authors.affiliation: Departments of Endocrinology and Metabolic Diseases, Leiden University Medical Center, Leiden, Netherlands.
authors.forename: Jacqueline T
authors.initials: JT
authors.lastname: Jonker
authors.forename: Johannes W A
authors.initials: JW
authors.lastname: Smit
authors.forename: Sebastiaan
authors.initials: S
authors.lastname: Hammer
authors.forename: Marieke
authors.initials: M
authors.lastname: Snel
authors.forename: Rutger W
authors.initials: RW
authors.lastname: van der Meer
authors.forename: Hildo J
authors.initials: HJ
authors.lastname: Lamb
authors.forename: Frits
authors.initials: F
authors.lastname: Mattijssen
authors.forename: Karin
authors.initials: K
authors.lastname: Mudde
authors.forename: Ingrid M
authors.initials: IM
authors.lastname: Jazet
authors.forename: Olaf M
authors.initials: OM
authors.lastname: Dekkers
authors.forename: Albert
authors.initials: A
authors.lastname: de Roos
authors.forename: Johannes A
authors.initials: JA
authors.lastname: Romijn
authors.forename: Sander
authors.initials: S
authors.lastname: Kersten
authors.forename: Patrick C N
authors.initials: PC
authors.lastname: Rensen
mesh_terms: D000328:Adult; D000075803:Angiopoietin-Like Protein 4; D042682:Angiopoietins / Q000097:blood*; D031204:Caloric Restriction; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000178:diet therapy*; D059305:Diet, High-Fat / Q000009:adverse effects; D002149:Energy Intake; D004797:Enzyme-Linked Immunosorbent Assay; D005215:Fasting / Q000009:adverse effects; D005230:Fatty Acids, Nonesterified / Q000097:blood*; D006801:Humans; D008297:Male; D008875:Middle Aged; D014280:Triglycerides / Q000097:blood; D015854:Up-Regulation; D055815:Young Adult
chemical_list: C474772:ANGPTL4 protein, human; D000075803:Angiopoietin-Like Protein 4; D042682:Angiopoietins; D005230:Fatty Acids, Nonesterified; D014280:Triglycerides