Table Info

Table 1.

Metrics of PBMCs mitochondrial function in MASLD

MASLD outcome	Mitochondrial function metric	Key findings	Reference
MASLD (non-biopsed, diagnosed by ultrasound)	Live mitochondria-specific energy changes in PBMCs, determined by Seahorse XFp analyzer.	The real-time assessment showed reduced mitochondrial respiration capacity in PBMCs from MASLD patients.	Garrafa E, 2023 [39]
MASLD (simple steatosis, estimated by using the FLI score)	Mitochondrial OXPHOS capacity, determined by proteomics analysis.	Increased OXPHOS capacity with complex I + II-linked substrates in PBMCs from MASLD.	Shirakawa R, 2023 [42]
MASLD (diagnosed by biopsy)	Measurement of serum mitochondrial respirometry and hepatic bioenergetic profiles.	Co-presence of loss-of-function polymorphisms in PNPLA3, TM6SF2, and MBOAT7 significantly predisposes individuals to MASLD progression.	Paolini E, 2024 [63]
MASLD (diagnosed by biopsy)	Maximal respiratory capacity.		Paolini E, 2024 [63]
MASLD [clinical diagnosis with at least 2 criteria (diabetes, biopsy, hypertriglyceridemia or under treatment, or CT or MRI imaging)]	Gene expression analysis related to inflammatory and metabolic pathways, determined by RNA sequencing.	The identified gene signatures showed enrichment in inflammation and metabolism pathways, suggesting their potential as diagnostic biomarkers for liver diseases.	Listopad S, 2022 [55]
MASLD/hepatic fibrosis (diagnosed by biopsy)	Live mitochondria-specific energy changes, determined by Seahorse XFp analyzer.	Significant reduction in mitochondrial energy consumption in PBMCs.	Ajaz S, 2021 [62]
MASH [diagnosed by biopsy (n = 43) or ultrasound]	mtDNA copy number as a proxy for mitochondrial mass, determined by transcriptomic analysis.	Reduced mtDNA copy number in PBMCs from MASLD patients compared to healthy subjects.	Lee AH, 2022 [41]
MASH (diagnosed by biopsy)	OPA1 (mitochondrial fusion marker), DRP1 (mitochondrial fission marker), and OPA1/DRP1 ratio (mitochondrial fusion/fission balance), determined by protein expression analysis by western blot.	Higher levels of OPA1 protein in MASH patients with significant fibrosis compared to those without fibrosis. Additionally, the OPA1/DRP1 ratio, indicating the balance between mitochondrial fusion and fission, was also higher in these patients.	Kunlayawutipong T, 2024 [59]

DRP1: dynamin-related protein 1; FLI: fatty liver disease; MASH: metabolic dysfunction-associated steatohepatitis; MASLD: metabolic dysfunction-associated steatotic liver disease; MBOAT7: membrane bound o-acyltransferase domain-containing 7; mtDNA: mitochondrial DNA; OPA1: optic atrophy 1; OXPHOS: oxidative phosphorylation; PBMCs: peripheral blood mononuclear cells; PNPLA3: patatin-like phospholipase domain-containing 3; RNA: ribonucleic acid; TM6SF2: transmembrane 6 superfamily member 2

Declarations

Author contributions

JNN, JR, MIRL, E Moreira, E Mateus, and EMR: Writing—original draft, Writing—review & editing. AJRA, BRM, and LOM: Writing—original draft, Writing—review & editing, Funding acquisition. MG: Conceptualization, Writing—original draft, Writing—review & editing. JJ: Conceptualization, Writing—original draft, Writing—review & editing, Funding acquisition. All authors read and approved the manuscript.

Conflicts of interest

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Ethical approval

Not applicable.

Consent to participate

Not applicable.

Consent to publication

Not applicable.

Availability of data and materials

Not applicable.

Funding

This research was supported by Consorcio Centro de Investigación Biomédica en Red – CIBER- de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM) (group [CB15/00071], leading group) and CIBER de Enfermedades Cardiovasculares (CIVERCV) [CB16/11/00257], Ministerio de Ciencia e Innovación Instituto de Salud Carlos III (ISCIII), Spain. MIRL holds a predoctoral grant from Pla Estratègic de Recerca i Innovació en Salut (PERIS) 2021-2024 of Generalitat de Catalunya [SLT017/20/000107]. JJ has received financial support from Agencia Estatal de Investigación (MCIN/AEI/10.13039/501100011033 and European Union “NextGeneration EU”/PRTR) within the action “Consolidación Investigadora 2022” [CNS2022-135559], and from Ministerio de Sanidad y Consumo, ISCIII [PI21/00770, PI24/00156], and Fondo Europeo de Desarrollo Regional (FEDER) “Una manera de hacer Europa”. BRM is supported by the “Miguel Servet” program, ISCIII, Spain; co-funded by the FEDER [CP19/00098]. AJRA was funded by Biomedical Research Institute of Murcia [IMIB/CI/09]. LOM has received funding from the IHU HealthAge [ANR-23-IAHU-0011]. Institut de Recerca de l’Hospital de la Santa Creu i Sant Pau (Institut de Recerca SANT PAU) is accredited by the Generalitat de Catalunya as Centre de Recerca de Catalunya (CERCA). JJ also belongs to the XARTEC Salut network, and is part of the coordinated consolidated group AGAUR [2021 SGR 00857, and 2021 SGR 01211]. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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