AUTHOR=Diaz Eva C. , Adams Sean H. , Weber Judith L. , Cotter Matthew , Børsheim Elisabet 

TITLE=Elevated LDL-C, high blood pressure, and low peak V̇O2 associate with platelet mitochondria function in children—The Arkansas Active Kids Study

JOURNAL=Frontiers in Molecular Biosciences

VOLUME=10

YEAR=2023

URL=https://www.frontiersin.org/journals/molecular-biosciences/articles/10.3389/fmolb.2023.1136975

DOI=10.3389/fmolb.2023.1136975

ISSN=2296-889X

ABSTRACT=<p><bold>Purpose:</bold> To evaluate the association of platelet (PL) mitochondria respiration with markers of cardiovascular health in children ages 7–10 years.</p><p><bold>Methods:</bold> 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<sub>E</sub>) were measured. The respiratory control ratio (RCR) was calculated as the ratio of maximal oxidative phosphorylation capacity of CI and CI leak respiration (P<sub>CI</sub>/L<sub>CI</sub>). Peak <inline-formula id="inf2"><mml:math id="m2" xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mrow><mml:mover accent="true"><mml:mi mathvariant="normal">V</mml:mi><mml:mo>̇</mml:mo></mml:mover></mml:mrow></mml:math></inline-formula>O<sub>2</sub> (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.</p><p><bold>Results:</bold> R and CI-linked respiration positively associated with adiposity, high blood pressure (HBP), and peak <inline-formula id="inf3"><mml:math id="m3" xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mrow><mml:mover accent="true"><mml:mi mathvariant="normal">V</mml:mi><mml:mo>̇</mml:mo></mml:mover></mml:mrow></mml:math></inline-formula>O<sub>2</sub>. R and CI-linked respiration had inverse association with age and elevated LDL-C. CII<sub>E</sub> was higher in children with elevated LDL-C (log-β = −0.54, <italic>p</italic> = 0.010). HBP and peak <inline-formula id="inf4"><mml:math id="m4" xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mrow><mml:mover accent="true"><mml:mi mathvariant="normal">V</mml:mi><mml:mo>̇</mml:mo></mml:mover></mml:mrow></mml:math></inline-formula>O<sub>2</sub> interacted in relation to RCR (log-β = −0.01, <italic>p</italic> = 0.028). Specifically, RCR was lowest among children with HBP and low aerobic capacity (i.e., mean peak <inline-formula id="inf5"><mml:math id="m5" xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mrow><mml:mover accent="true"><mml:mi mathvariant="normal">V</mml:mi><mml:mo>̇</mml:mo></mml:mover></mml:mrow></mml:math></inline-formula>O<sub>2</sub> -1SD). HOMA2-IR did not associate with measures of PL mitochondria respiration.</p><p><bold>Conclusion:</bold> In PL, R and CI-linked mitochondrial respiration directly associate with adiposity, peak <inline-formula id="inf6"><mml:math id="m6" xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mrow><mml:mover accent="true"><mml:mi mathvariant="normal">V</mml:mi><mml:mo>̇</mml:mo></mml:mover></mml:mrow></mml:math></inline-formula>O<sub>2</sub> 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.</p>