A COMPREHENSIVE DOSE-RESPONSE STUDY OF THE EFFECTS OF PISTACHIOS ON CARDIOVASCULAR DISEASE RISK FACTORS: A TRANSLATIONAL RESEARCH APPROACH INTEGRATING CLINICAL NUTRITION AND MOLECULAR BIOLOGY

Open Access
Author:
Gebauer, Sarah K
Graduate Program:
Integrative Biosciences
Degree:
Doctor of Philosophy
Document Type:
Dissertation
Date of Defense:
March 05, 2008
Committee Members:
  • Penny Margaret Kris Etherton, Committee Chair
  • John Patrick Vanden Heuvel, Committee Member
  • Sheila Grace West, Committee Member
  • David Theodore Mauger, Committee Member
Keywords:
  • peripheral blood mononuclear cells
  • cholesteryl ester transfer protein
  • cardiovascular disease risk
  • pistachios
  • lipids and lipoproteins
  • translational research
Abstract:
Nut consumption reduces risk for cardiovascular disease (CVD). Few studies have evaluated the effects of pistachios on CVD risk factors and they have not evaluated dose-response relationships or lipid-lowering mechanisms. Nutrition studies with a translational research approach integrate clinical nutrition and molecular biology, allowing for the investigation of clinical responses and underlying cellular mechanisms. The present study utilized a translational research approach to comprehensively evaluate the effects of pistachios on CVD. We employed a randomized crossover controlled-feeding study to evaluate the effects of two doses of pistachios, added to a lower-fat diet, on lipids and lipoproteins, apolipoprotein-defined lipoprotein subclasses, and plasma fatty acids. To investigate mechanisms of action, we measured serum cholesteryl ester transfer protein (CETP), indices of plasma stearoyl-CoA desaturase activity (SCD), and gene expression in isolated peripheral blood mononuclear cells (PBMCs). Total cholesterol (TC), LDL-C, non-HDL-C, apoB, and apoB/apoA-I decreased after both pistachio diets; and triacylglycerol and plasma SCD activity decreased after the 3.0 ounce pistachio diet (P < 0.05). Pistachios elicited a dose-dependent lowering of TC/HDL-C, LDL-C/HDL-C, and non-HDL-C/HDL-C (P < 0.01). We evaluated the effects of pistachios on expression of genes related to inflammation and lipid metabolism (TNFá, IL-1â, IL-6, ICAM, VCAM, CETP, and LCAT) in PBMCs. Furthermore, we investigated the relationship between diet-induced change in CETP expression and change in serum CETP and plasma lipids/lipoproteins. The pistachio-rich diets significantly decreased IL-1â expression compared to baseline (P < 0.05). Change in CETP expression in PBMCs predicted change in LDL-C, NONHDL-C, TC/HDL-C, and NONHDL-C/HDL-C in individuals who were diet-responsive with regards to serum CETP. In conclusion, this study demonstrates that pistachios elicit beneficial effects on traditional and emerging CVD risk factors at the protein level in serum/plasma and the transcription level in PBMCs.