Oral Presentation Australian & New Zealand Obesity Society 2015 Annual Scientific Meeting

Grand-paternal obesity affects female grand-offspring metabolic pathways (#40)

Virginie Lecomte 1 , Chris A Maloney 1 , Margaret J Morris 1
  1. School of Medical Sciences, UNSW Australia, Sydney, NSW, Australia

Parental obesity is a major predictor of child obesity. Moreover, emerging evidence in humans associates nutrition of the grand-parents with metabolic and cardiovascular diseases in grand-offspring1. Our lab developed a robust model of paternal obesity and showed that female offspring from obese fathers developed glucose intolerance and insulin secretion impairment2. To model human transgenerational transmission of metabolic risk, we extended our investigation to determine whether metabolic defects could be passed on from grandfather to female grand-offspring.

High fat (HFD) and control (CD) diet fed F0 male rats were mated after 12 weeks of diet with control fed females. F1 male offspring were weaned onto CD and mated with control fed females at 14 weeks of age. The resulting F2 female offspring were weaned either onto HFD or CD.

F2 female offspring from HFD F0 developed glucose intolerance at 12 weeks of age when fed a HFD. Liver and Tibialis Anterioris muscle samples were collected from 14 week old female F2 for gene expression analysis using Life Technologies Open Array platform. Expression of 168 metabolism regulating genes was assayed. Having a HFD fed grandfather significantly changed the expression of 22 genes in liver and 15 genes in muscle of F2 female grand-offspring. Pathway analysis using DAVID gene functional classification and ConsensusPathDB interaction analysis revealed that the main pathways influenced by grand-paternal nutrition in the liver were glucose metabolism and insulin signalling. In muscle, fatty acid synthesis and metabolism were the main pathways influenced by F0 status.

These data show, for the first time in a rodent model of diet-induced obesity, a direct effect of grand-paternal obesity on regulation of metabolic pathways in grand-offspring.