Mitochondrial oxidative capacity is decreased in peripheral blood mononuclear cells after chronic amino acid supplementation in older adults with hypertriacylglycerolaemia
Authors: Carvalho Eugenia , Rose Shannon , Hurren Nicholas M , Cotter Matthew , Azhar Gohar , Schutzler Scott , Frye Richard , Borsheim Elisabet 
Published: November 2023

Background

Several studies have reported that skeletal muscle mitochondrial respiratory capacity is lower in older adults than in young adults, suggesting that mitochondrial dysfunction may occur as a consequence of the aging process. In addition, blood‐cell bioenergetics has been suggested as an indicator of systemic mitochondrial health. We have shown that supplementation with essential amino acids (EAAs) plus arginine decreases plasma and liver triacylglycerols in older adults (1). However, no studies to date have reported the impact of such supplementation on mitochondrial respiration within circulating cells. The purpose of this study was to assess the effect of eight weeks of EAA + arginine supplementation on circulating cell bioenergetics in older adults with hypertriacylglycerolaemia.

Methods

Six (two men) older adults (age: 68.8±2.0 years) underwent testing before and after 8 weeks of supplementation with EAA + arginine (11 g of AAs ingested twice daily). Specifically, a skeletal muscle biopsy, peripheral blood mononuclear cells (PBMCs; n=4), and platelets (n=4) were collected pre‐ and post‐supplementation, in order to measure mitochondrial function by high‐resolution respirometry using the Oroboros and the Seahorse, respectively. Mitochondrial respiration was determined in permeabilized myofibers from the m. vastus lateralis after the addition of substrates, oligomycin, and FCCP. Thereafter, mitochondrial coupling control was calculated.

Results

Maximal coupled respiration (respiration linked to ATP production) in muscle was not significantly changed by 8 weeks of AA supplementation. On the other hand, ATP‐linked respiration (31.55±4.43 vs. 18.93±2.89 pmol/min, p=0.05), maximal respiration (127±25 vs. 60±9 pmol/min, p=0.05) and the reserve capacity (94.2±21.7 vs. 40.1±6.2, pmol/min, p=0.05) were decreased in isolated PBMCs following 8 weeks of supplementation. While no significant differences in mitochondrial respiration were observed for platelets, the glycolytic capacity of platelets was decreased (70.3±0.8 vs. 55.3±2.6 mpH/min, p=0.03) after AA supplementation. No significant alterations in glycolysis were observed in PBMCs.

Conclusions

These results indicate that EAA supplementation may lower respiration rates in PBMCs. The mechanisms underlying this may be that lowering lipids as previously observed decreases stress on cells and therefore lowers ATP demand, or that the substrate pool is altered and thus metabolism shifted. Future studies are needed in order to elucidate mechanisms and understand the implications of these novel findings.

Support or Funding Information

Funding: NIH R01‐AG033761, NIH P30‐AG028718, Arkansas Biosciences Institute the major research component of the Arkansas Tobacco Settlement Proceeds Act of 2000, FEDER funds through the Operational Programme Competitiveness Factors ‐ COMPETE and UID/NEU/04539/2013