Transient postnatal overfeeding causes liver stress-induced premature senescence in adult mice View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2017-12

AUTHORS

Catherine Yzydorczyk, Na Li, Hassib Chehade, Dolores Mosig, Mickael Bidho, Basile Keshavjee, Jean Baptiste Armengaud, Katya Nardou, Benazir Siddeek, Mohamed Benahmed, Catherine Vergely, Umberto Simeoni

ABSTRACT

Unbalanced nutrition early in life is increasingly recognized as an important factor in the development of chronic, non-communicable diseases at adulthood, including metabolic diseases. We aimed to determine whether transient postnatal overfeeding (OF) leads to liver stress-induced premature senescence (SIPS) of hepatocytes in association with liver structure and hepatic function alterations. Litters sizes of male C57BL/6 mice were adjusted to 9 pups (normal feeding, NF) or reduced to 3 pups during the lactation period to induce transient postnatal OF. Compared to the NF group, seven-month-old adult mice transiently overfed during the postnatal period were overweight and developed glucose intolerance and insulin resistance. Their livers showed microsteatosis and fibrosis, while hepatic insulin signaling and glucose transporter protein expressions were altered. Increased hepatic oxidative stress (OS) was observed, with increased superoxide anion production, glucose-6-phosphate dehydrogenase protein expression, oxidative DNA damage and decreased levels of antioxidant defense markers, such as superoxide dismutase and catalase proteins. Hepatocyte senescence was characterized by increased p21WAF, p53, Acp53, p16INK4a and decreased pRb/Rb and Sirtuin-1 (SIRT-1) protein expression levels. Transient postnatal OF induces liver OS at adulthood, associated with hepatocyte SIPS and alterations in liver structure and hepatic functions, which could be mediated by a SIRT-1 deficiency. More... »

PAGES

12911

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/s41598-017-11756-2

DOI

http://dx.doi.org/10.1038/s41598-017-11756-2

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1092092317

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/29018245


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