Aging Cell

High-fat diet effects persist in lab-grown rat liver structures

Experiments using liver structures grown from high-fat-fed male rats found persistent changes resembling senescence, a state in which cells stop dividing.

Graphical abstract from Aging Cell
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Graphical abstract. Yamazaki et al.
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In experiments in male rats, researchers tested whether a high-fat diet left lasting changes in cells involved in liver regeneration. High-fat-fed rats developed liver fat accumulation, inflammation and changes associated with senescence. After chemically induced liver injury, they showed reduced cell division.

The team then grew liver organoids, three-dimensional cell structures, from high-fat-fed and control rats. Those from high-fat-fed rats formed less efficiently and had a reduced ability to keep growing through repeated transfers outside their original metabolic environment. Senescence-associated changes persisted through the third passage, a transfer to continue growth. These organoids also showed dysfunction in mitochondria, the cells’ energy-producing structures. MitoQ, an antioxidant that targets mitochondria, reduced the release of inflammatory substances and partly restored organoid formation.

Why it matters

Chronic metabolic stress is linked to aging-like tissue dysfunction. This work examined whether its consequences extend to the cells involved in liver maintenance and repair.

Caveats

Persistence outside the original metabolic environment was tested in lab-grown organoids, not intact animals. The study used male rats and did not establish whether the same changes occur in people.