Eight weeks of daily cottonseed oil intake attenuates postprandial angiopoietin-like proteins 3 and 4 responses compared to olive oil in adults with hypercholesterolemia: A secondary analysis of a randomized clinical trial.

Angiopoietin-like proteins (ANGPTLs) -3, -4, and -8 are regulators of lipid metabolism and have been shown to respond to changes in dietary fats. It is unknown how ANGPTLs respond to cottonseed oil (CSO) and olive oil (OO) consumption in a population with hypercholesterolemia. The purpose of this study was to determine the impact of CSO vs. OO consumption on fasting and postprandial ANGPTL responses in adults with hypercholesterolemia. We hypothesized that CSO would have lower fasting and postprandial ANGPTL responses compared with OO. Forty-two adults with high cholesterol completed a single-blind, randomized trial comparing CSO (n = 21) vs. OO (n = 21) diet enrichment. An 8-week partial outpatient feeding intervention provided ∼60% of the volunteers' total energy expenditure (∼30% of total energy expenditure as CSO or OO). The remaining 40% was not controlled. Fasting blood draws were taken at pre-, mid-, and postintervention visits. Volunteers consumed a high saturated fat meal followed by 5 hours of blood draws pre- and postvisits. Fasting ANGPTL3 had a marginally significant treatment by visit interaction (P = .06) showing an increase from pre- to postintervention in CSO vs. OO (CSO: 385.1 ± 27.7 to 440.3 ± 33.9 ng/mL; OO: 468.2 ± 38.3 to 449.2 ± 49.5 ng/mL). Both postprandial ANGPTL3 (P = .02) and ANGPTL4 (P < .01) had treatment by visit interactions suggesting increases from pre- to postintervention in OO vs. CSO with no differences between groups in ANGPTL8. These data show a worsening (increase) of postprandial ANGPTLs after the OO, but not CSO, intervention. This aligns with previously reported data in which postprandial triglycerides were protected from increases compared with OO. ANGPTLs may mediate protective effects of CSO consumption on lipid control. This trial was registered at clinicaltrials.gov (NCT04397055).

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Declaration of Competing Interest The authors have no conflicts of interest to declare.