Grandpaternal exposure to altered food availability during the slow growth period is associated with a greater risk for obesity and cardiovascular disease in grandchildren, while parental diabetes at conception is associated with altered birth weight and increased risk of diabetes in the offspring. When phenotypic changes in the first generation are similar to or the same as the inducing stressor, this can, in turn, program the phenotype of the second generation by a process known as serial programming. While adipose tissue is one of the major sites of paternal high caloric intake-induced transgenerational reprogramming, less is known regarding the impact of parental diet on skeletal muscle physiology and metabolism.
Alm, de Castro Barbosa et al. determined the transgenerational response of paternal diet-induced obesity on the skeletal muscle transcriptome and lipidome. Transcriptomic analysis revealed that grand-offspring of diet-induced obese founders present altered unfolded protein response in skeletal muscle, possibly triggered by the activation of the stress-sensor Activating transcription factor 6, irrespective of changes in the lipidomic profile. These transgenerational epigenetic effects may be mitigated or aggravated by the diet composition in offspring. These findings advance the notion that paternal exposure to environmental factors program whole-body and tissue-specific features, affecting the development and health of successive generations.Full Text