Key result
Maternal Western diet reduces macaque hepatic mitochondrial respiration by ~50% independent of postweaning diet.
Why the study?
Children born to mothers with obesity are more likely to develop MASLD, and this study investigates how maternal Western diet exposure alters hepatic mitochondria in nonhuman primate offspring.
Does maternal Western diet exposure alter hepatic mitochondrial function and organization in juvenile macaque offspring?
Does maternal Western diet exposure alter hepatic mitochondrial function and organization in juvenile macaque offspring?
Maternal Western diet exposure programs hepatic mitochondrial dysfunction and oxidative stress in offspring, contributing to MASLD risk independent of the offspring's own diet.
Maternal Western diet may program offspring mitochondrial dysfunction independent of postnatal diet; leaves open relevance to human MASLD risk.
Introduction and Objective: Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common chronic liver disease in children and adults. Children born to mothers with obesity are more likely to develop MASLD. Mitochondrial dysfunction is common in offspring exposed to maternal Western diet (mWD, high fat/sugar) during gestation and lactation. This study investigates how mWD exposure alters hepatic mitochondria in the context of MASLD in 3 y.o. nonhuman primate offspring. Methods: Japanese macaques born to chow-fed (mCD) or mWD-fed dams were weaned onto chow diet (CD) or WD from ~7 m.o. until necropsy 2.5 y later: CD/CD (n=6), CD/WD (n=4), WD/CD (n=7), and WD/WD (n=9). Triglyceride (TG) content, TBARS, and collagen were measured in offspring liver. Hepatic mitochondria were enriched from frozen liver to assay function (Seahorse) and organization (BN-PAGE) of key respiratory complexes: CI, CIV, and CV. Results: CI-linked respiration was ~35% lower in groups weaned to WD, and ~50% in WD/WD relative to CD/CD offspring. CIV-linked respiration was reduced in mWD groups regardless of postweaning diet. Respiratory complexes organized into supercomplexes (SCs) containing CI, CIV and CV, which improves efficiency and prevents oxidative damage, were measured. CI- and CIV-SCs were decreased in WD animals, particularly those exposed to mWD. CV-SCs content was unchanged. Linear regression revealed relationships between: CI-SCs and fibrosis; CIV-SCs and TBARS; CV-SCs and TGs. mWD resulted in decreased stress responders like SOD2 in offspring liver. Conclusion: Losses in mitochondrial SC function and organization associate with features of MASLD in juvenile nonhuman primates exposed to mWD. mWD programming aligns with CIV dysfunction, less antioxidant capacity, and higher redox stress independent of offspring diet. Together, these discoveries emphasize the importance of specific mitochondrial shifts and MASLD risk. Disclosure K.T. Greyslak: None. M.J. Nash: None. R. Janssen: None. S.R. Wesolowski: None. J. Friedman: None. Funding NIH R24-DK090964 (J.E.F.), NIH R01-DK128416 (J.E.F.), NIH F30-DK122672 (M.J.N.), NIH R01-DK108910 (S.R.W.), NIH P30-DK048520 (J.E.F.)
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Greyslak et al. (2026) studied Metabolic dysfunction-associated steatotic liver disease (MASLD) (n=26). Maternal Western diet (mWD) vs. Maternal chow diet (mCD) was evaluated on Hepatic mitochondrial function and supercomplex organization. Maternal Western diet exposure in juvenile macaques reduced CI-linked respiration by up to 50% and decreased mitochondrial supercomplex organization, independent of the offspring's postweaning diet.
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