Maternal high-fat diet promotes body length increases and insulin insensitivity in second-generation mice.
Maternal obesity and diet consumption during pregnancy have been linked to offspring adiposity, cardiovascular disease, and impaired glucose metabolism. Furthermore, nutrition during development is clearly linked to somatic growth. However, few studies have examined whether phenotypes derived from maternal high-fat diet exposure can be passed to subsequent generations and by what mechanisms this may occur. Here we report the novel finding of a significant body length increase that persisted across at least two generations of offspring in response to maternal high-fat diet exposure. This phenotype is not attributable to altered intrauterine conditions or maternal feeding behavior because maternal and paternal lineages were able to transmit the effect, supporting a true epigenetic manner of inheritance. We also detected a heritable feature of reduced insulin sensitivity across two generations. Alterations in the GH secretagogue receptor (GHSR), the GHSR transcriptional repressor AF5q31, plasma IGF-I concentrations, and IGF-binding protein-3 (IGFBP3) suggest a contribution of the GH axis. These studies provide evidence that the heritability of body length and glucose homeostasis are modulated by maternal diet across multiple generations, providing a mechanism where length can increase rapidly in concert with caloric availability.
Dunn
Gregory A
GA
University of Pennsylvania, Department of Animal Biology, 201E Vet, 6046, 3800 Spruce Street, Philadelphia, Pennsylvania 19104-6046, USA.
Bale
Tracy L
TL
D050154:Adiposity; D000818:Animals; D001786:Blood Glucose; D001827:Body Height; D001835:Body Weight; D019175:DNA Methylation; D004041:Dietary Fats / Q000009:adverse effects*; D005260:Female; D006801:Humans; D007333:Insulin Resistance; D008297:Male; D039382:Maternal Nutritional Physiological Phenomena; D051379:Mice; D008810:Mice, Inbred C57BL; D023421:Models, Animal; D009765:Obesity / Q000209:etiology / Q000235:genetics / Q000378:metabolism*; D010375:Pedigree; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D054440:Receptors, Ghrelin / Q000235:genetics / Q000378:metabolism
D001786:Blood Glucose; D004041:Dietary Fats; D054440:Receptors, Ghrelin