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Neonatal overfeeding accelerates age-related sarcopenia and metabolic disorders through lifelong gut mucosa and microbiota programming

ABSTRACT: Early-life nutrition shapes lifelong health, yet the long-term consequences of childhood overnutrition, particularly on musculoskeletal aging, remain unclear. To address this gap, we employed an established neonatal overfeeding model by reducing litter size, assigning litters to either 4 pups per dam (Overfed group) or 8 pups per dam (Normal-fed control group). To directly examine whether microbiota alterations mediate neonatal overnutrition-induced acceleration of sarcopenia, we performed fecal microbiota transplantation (FMT) experiments. We transplanted microbiota from either aged normal-fed or overfed donor mice into adult recipients (rNormal and rOver groups) maintained on a high-fat diet (HFD) for 20 weeks to accelerate the onset of metabolic and muscular dysfunction. These findings reveal a developmental origin of age-related sarcopenia and define a gut-muscle axis linking childhood overnutrition to muscle aging.

ORGANISM(S): Mus musculus

PROVIDER: GSE305875 | GEO | 2026/08/27

REPOSITORIES: GEO

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Project description:Myelin is a natural and dynamic multilamellar membrane structure that continues to be of significant biological and neurological interest, especially with respect to its biosynthesis and assembly during its normal formation and maintenance, and pathological breakdown. To explore the usefulness of neutron diffraction in the structural analysis of myelin, we investigated the use of in vivo labeling by metabolically incorporating non-toxic levels of deuterium (2H; D) via drinking water into a pregnant dam (D-dam) and her developing embryos. All of the mice were sacrificed when the pups (D-pups) were 55 days old. Myelinated sciatic nerves were dissected, fixed in glutaraldehyde and examined by neutron diffraction. Parallel samples that were unfixed (trigeminal nerves) were frozen for mass spectrometry (MS). The diffraction patterns of the nerves from deuterium-fed mice (D-mice) versus the controls (H-mice) had major differences in the intensities of the Bragg peaks but no appreciable differences in myelin periodicity. Neutron scattering density profiles showed an appreciable increase in density at the center of the lipid-rich membrane bilayer This increase was greater in D-pups than in D-dam, and its localization was consistent with deuteration of lipid hydrocarbon, which predominates over transmembrane protein in myelin. MS analysis of the lipids isolated from the trigeminal nerves demonstrated that in the pups the percentage of lipids that had one or more deuterium atoms was uniformly high across lipid species (97.6% ± 2.0%), whereas in the mother the lipids were substantially less deuterated (60.6% ± 26.4%) with the levels varying among lipid species and subspecies. The mass distribution pattern of deuterium-containing isotopologues indicated the fraction (in %) of each lipid (sub-)species having one or more deuteriums incorporated: in the D-pups, the pattern was always bell-shaped, and the average number of D atoms ranged from a low of ~4 in fatty acid to a high of ~9 in cerebroside. By contrast, in D-dam most lipids had more complex, overlapping distributions that were weighted toward a lower average number of deuteriums, which ranged from a low of ~3–4 in fatty acid and in one species of sulfatide to a high of 6–7 in cerebroside and sphingomyelin. The consistently high level of deuteration in D-pups can be attributed to their de novo lipogenesis during gestation and rapid, postnatal myelination. The widely varying levels of deuteration in D-dam, by contrast, likely depends on the relative metabolic stability of the particular lipid species during myelin maintenance. Our current findings demonstrate that stably-incorporated D label can be detected and localized using neutron diffraction in a complex tissue such as myelin; and moreover, that MS can be used to screen a broad range of deuterated lipid species to monitor differential rates of lipid turnover. In addition to helping to develop a comprehensive understanding of the de novo synthesis and turnover of specific lipids in normal and abnormal myelin, our results also suggest application to studies on myelin proteins (which constitute only 20–30% by dry mass of the myelin, versus 70–80% for lipid), as well as more broadly to the molecular constituents of other biological tissues.

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Neonatal overfeeding accelerates age-related sarcopenia and metabolic disorders through lifelong gut mucosa and microbiota programming

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