Baseline Insulin Resistance Is a Determinant of the Small, Dense Low-Density Lipoprotein Response to Diets Differing in Saturated Fat, Protein, and Carbohydrate Contents.

Xiuzhi Wu,Penny M Kris-Etherton,Alison M Hill,Michael A Roussell,Rosemary L Walzem

doi:10.3390/nu13124328

Xiuzhi Wu, Penny M Kris-Etherton + Show 3 more

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https://doi.org/10.3390/nu13124328

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Journal: Nutrients	Publication Date: Nov 30, 2021
Citations: 5	License type: CC BY 4.0

Affiliation: Pennsylvania State University, Texas A&M University

Abstract

Individual responses to diet vary but causes other than genetics are poorly understood. This study sought to determine whether baseline values of homeostasis model assessment (HOMA-IR) was related to changes in small, dense low-density lipoprotein (sdLDL, i.e., LDL4, d = 1.044–1.063 g/mL) amounts quantified by isopycnic density profiling, in mildly hypercholesterolemic subjects (n = 27) consuming one of three low saturated fatty acid (SFA) diets: Dietary Approaches to Stop Hypertension (DASH), Beef in an Optimal Lean Diet (BOLD) and BOLD plus extra protein (BOLD+) when compared to a higher-SFA healthy American diet (HAD). The diets were consumed in random order for 5 wk, with 1 wk between diets. BOLD+ reduced fractional abundance (%) LDL4 (p < 0.05) relative to HAD, DASH and BOLD, and reductions in % LDL4 correlated with reductions in triglycerides (p = 0.044), total cholesterol (p = 0.014), LDL cholesterol (p = 0.004) and apolipoprotein B (p < 0.001). Responses to the four diets were similar (~12% decrease in % LDL4, p = 0.890) in the lower (<2.73 median) HOMA-IR subgroup but differed across diet conditions in the higher HOMA-IR subgroup (p = 0.013), in which % LDL4 was reduced with BOLD+ (−11%), was unchanged in BOLD and increased with the HAD (8%) and DASH (6%) diets (p < 0.05 for BOLD+ vs. HAD). Individual responses to diet interventions are influenced by presence and degree of insulin resistance as measured by HOMA-IR.

Highlights

Low-density lipoprotein (LDL) particles are highly heterogeneous, and likely vary in atherogenicity due to differences in size, composition, and physiochemical properties.Compared with larger LDL particles, small dense LDL particles have a higher propensity to penetrate the artery wall and bind to proteoglycans [1], increased susceptibility to oxidation [2] and reduced affinity for the LDL receptor [3]
No differences were observed for TG, HDL cholesterol (HDL-C), CRP and HOMA-IR between men and women
We show that cholesterol decrement was associated with a 9.2% decrease in the small dense LDL (sdLDL) (i.e., LDL4 ) species that is thought to be the most atherogenic, consistent with a shift toward a less atherogenic distribution of LDL

Summary

Introduction

Low-density lipoprotein (LDL) particles are highly heterogeneous, and likely vary in atherogenicity due to differences in size, composition, and physiochemical properties.Compared with larger LDL particles, small dense LDL (sdLDL) particles have a higher propensity to penetrate the artery wall and bind to proteoglycans [1], increased susceptibility to oxidation [2] and reduced affinity for the LDL receptor [3]. A higher level of sdLDL particles is associated with increased risk for ischemic heart disease [4]. Lifestyle change to alter modifiable risk factors is often the first strategy to reduce ischemic heart disease, with reductions in total and LDL cholesterol (LDL-C) being key targets for reduction. Compared with an isocaloric high-fat diet, low fat/high carbohydrate diets are associated with either no change or a decrease in LDL particle diameter (i.e., a shift toward sdLDL) [5,6,7,8,9]. Replacement of carbohydrate by protein (from plant or animal sources) in moderate- or high-fat eucaloric diets is generally associated with an improved LDL density profile, with a shift away from sdLDL toward larger, more buoyant LDL subfractions [8,10,11]

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