Elevated LDL-C, high blood pressure, and low peak [Formula: see text] O2 associate with platelet mitochondria function in children-The Arkansas Active Kids Study

Eva C Diaz; Sean H Adams; Judith L Weber; Matthew Cotter; Elisabet Børsheim

doi:10.3389/fmolb.2023.1136975

Elevated LDL-C, high blood pressure, and low peak $\dot{V}$ O₂ associate with platelet mitochondria function in children-The Arkansas Active Kids Study

Front Mol Biosci. 2023 Mar 22:10:1136975. doi: 10.3389/fmolb.2023.1136975. eCollection 2023.

Authors

Eva C Diaz^{1

2

3}, Sean H Adams⁴, Judith L Weber^{2

5}, Matthew Cotter¹, Elisabet Børsheim^{1

2

3}

Affiliations

¹ Arkansas Children's Nutrition Center, Little Rock, AR, United States.
² Arkansas Children's Research Institute, Little Rock, AR, United States.
³ Department of Pediatrics, College of Medicine, University of Arkansas for Medical Sciences, Little Rock, AR, United States.
⁴ Department of Surgery, and Center for Alimentary and Metabolic Science, University of California, Davis, School of Medicine, Sacramento, CA, United States.
⁵ Department of Nursing Science, College of Nursing, University of Arkansas for Medical Sciences, Little Rock, AR, United States.

Abstract

Purpose: To evaluate the association of platelet (PL) mitochondria respiration with markers of cardiovascular health in children ages 7-10 years. Methods: PL mitochondrial respiration (n = 91) was assessed by high resolution respirometry (HRR): Routine (R) respiration, complex (C) I linked respiration (CI), and maximal uncoupled electron transport capacity of CII (CII_E) were measured. The respiratory control ratio (RCR) was calculated as the ratio of maximal oxidative phosphorylation capacity of CI and CI leak respiration (P_CI/L_CI). Peak $\dot{V}$ O₂ (incremental bike test) and body composition (dual-energy X-ray absorptiometry) were measured. Multiple generalized linear regression analysis was used to model the association of measures by HRR with variables of interest: adiposity, low-density lipoprotein (LDL-C) and triglyceride (TG) status (normal vs. elevated) HOMA2-IR, blood pressure status (normal vs. high), and demographics. Results: R and CI-linked respiration positively associated with adiposity, high blood pressure (HBP), and peak $\dot{V}$ O₂. R and CI-linked respiration had inverse association with age and elevated LDL-C. CII_E was higher in children with elevated LDL-C (log-β = -0.54, p = 0.010). HBP and peak $\dot{V}$ O₂ interacted in relation to RCR (log-β = -0.01, p = 0.028). Specifically, RCR was lowest among children with HBP and low aerobic capacity (i.e., mean peak $\dot{V}$ O₂ -1SD). HOMA2-IR did not associate with measures of PL mitochondria respiration. Conclusion: In PL, R and CI-linked mitochondrial respiration directly associate with adiposity, peak $\dot{V}$ O₂ and HBP. Elevated LDL-C associates with lower CI-linked respiration which is compensated by increasing CII respiration. PL bioenergetics phenotypes in children associate with whole-body metabolic health status.

Keywords: aerobic capacity; blood platelets; body composition; cardiometabolic risk (factors); mitochondria.

Grants and funding

This work was funded by USDA-ARS Projects 3092-51000-056- 04A and 6026-51000-012-06S. ED, EB, MC, and JW are partially supported by NIH-NIGMS award 5P20GM109096.