Paternal obesity decreases infant MSC mitochondrial functional capacity.
Am J Physiol Endocrinol Metab
; 327(4): E441-E448, 2024 Oct 01.
Article
en En
| MEDLINE
| ID: mdl-39140975
ABSTRACT
Besides the well-recognized influence of maternal health on fetal in utero development, recent epidemiological studies appoint paternal preconception metabolic health as a significant factor in shaping fetal metabolic programming and subsequently offspring metabolic health; however, mechanisms behind these adaptations remain confined to animal models. To elucidate the effects of paternal obesity (P-OB) on infant metabolism in humans, we examined mesenchymal stem cells (MSCs), which give rise to infant tissue, remain involved in mature tissue maintenance, and resemble the phenotype of the offspring donor. Here, we assessed mitochondrial functional capacity, content, and insulin action in MSC from infants of fathers with overweight [body mass index (BMI 25-30 kg/m2); paternal overweight (P-OW)] or obesity (BMI ≥ 30 kg/m2; P-OB) while controlling for maternal intrauterine environment. Compared with P-OW, infant MSCs in the P-OB group had lower intact cell respiration, OXPHOS, and electron transport system capacity, independent of any changes in mitochondrial content. Furthermore, glucose handling, insulin action, lipid content, and oxidation were similar between groups. Importantly, infants in the P-OB group had a greater weight-to-length ratio, which could be in part due to changes in MSC metabolic functioning, which precedes and, therefore, influences infant growth trajectories. These data suggest that P-OB negatively influences infant MSC mitochondria. ClinicalTrials.gov Identifier NCT03838146.NEW & NOTEWORTHY Paternal obesity decreases infant mesenchymal stem cell (MSC) basal and maximal respiration. Lower OXPHOS and electron transport system capacity could be explained by lower complex I and IV respiratory capacity but not changes in OXPHOS expression in infant MSC from fathers with obesity. Paternal obesity and altered MSC mitochondrial functional capacity are associated with a greater infant weight-to-length ratio at birth.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Padre
/
Células Madre Mesenquimatosas
/
Mitocondrias
/
Obesidad
Límite:
Adult
/
Female
/
Humans
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Infant
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Male
/
Newborn
/
Pregnancy
Idioma:
En
Revista:
Am J Physiol Endocrinol Metab
Asunto de la revista:
ENDOCRINOLOGIA
/
FISIOLOGIA
/
METABOLISMO
Año:
2024
Tipo del documento:
Article
País de afiliación:
Estados Unidos
Pais de publicación:
Estados Unidos