Epigenetic germline inheritance of diet-induced obesity and insulin resistance

The “gamete” is the mature haploid germ cell that is either male (sperm) or female (oocyte).  There is considerable controversy regarding epigenetic inheritance in mammalian gametes. Using ex vivo fertilization to ensure exclusive inheritance via the gametes, authors [see attached] showed that a parental high-fat diet renders offspring more susceptible to developing obesity and diabetes in a sex-specific, and parent-of-origin–specific mode. These data provide strong evidence that the epigenetic inheritance of acquired metabolic disorders most likely contributes to the current obesity and diabetes pandemic that we see in Western societies.

How maternal diet influences offspring metabolism has been unclear, because it is difficult to distinguish between the effects of the in utero environment, versus the effects of epigenetic factors contributed by the oocyte.  In this mouse model of high-fat diet [below], this convincing study dissects these mechanisms by using ex vivo fertilization and shows that susceptibility of offspring to diet-induced obesity and insulin resistance can most likely be attributed to epigenetic inheritance via the oocyte.

Nat Genet May 2o16; 48: 497–499;   and editorial, pp 478–479

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