Chronic high-fat diet in fathers programs β-cell dysfunction in female rat offspring

By Sheau-Fang Ng, R. C. Lin, D. R. Laybutt, R. Barrès, J. Owens, M. Morris. Nature, 2010

1,325 citations recorded by the source corpus.

The global prevalence of obesity is increasing across most ages in both sexes. This is contributing to the early emergence of type 2 diabetes and its related epidemic. Having either parent obese is an independent risk factor for childhood obesity. Although the detrimental impacts of diet-induced maternal obesity on adiposity and metabolism in offspring are well established, the extent of any contribution of obese fathers is unclear, particularly the role of non-genetic factors in the causal pathway. Here we show that paternal high-fat-diet (HFD) exposure programs β-cell ‘dysfunction’ in rat F1 female offspring. Chronic HFD consumption in Sprague–Dawley fathers induced increased body weight, adiposity, impaired glucose tolerance and insulin sensitivity. Relative to controls, their female offspring had an early onset of impaired insulin secretion and glucose tolerance that worsened with time, and normal adiposity. Paternal HFD altered the expression of 642 pancreatic islet genes in adult female offspring (P < 0.01); genes belonged to 13 functional clusters, including cation and ATP binding, cytoskeleton and intracellular transport. Broader pathway analysis of 2,492 genes differentially expressed (P < 0.05) demonstrated involvement of calcium-, MAPK- and Wnt-signalling pathways, apoptosis and the cell cycle. Hypomethylation of the Il13ra2 gene, which showed the highest fold difference in expression (1.76-fold increase), was demonstrated. This is the first report in mammals of non-genetic, intergenerational transmission of metabolic sequelae of a HFD from father to offspring.

Subfields: Pediatrics, Perinatology and Child Health, Physiology, Surgery

View Paper: https://www.semanticscholar.org/paper/731e85b35b62acaa2d203592bb3610dc74ed94f1

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In Pediatrics, Perinatology and Child Health

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Citations in the corpus

Paternally-induced transgenerational environmental reprogramming of metabolic gene expression in mammals (2010, background): “, 2006), and chronic exposure of male rats to high-fat diet affects pancreatic islet biology in offspring (Ng et al., 2010).”
Paternal stress exposure alters sperm microRNA content and reprograms offspring HPA stress axis regulation (2013, background): “Research from rodent models of male exposure to dietary challenge, drugs of abuse, or social defeat support the transmission of paternal experiences to offspring through epigenetic marks in sperm (Carone et al., 2010; Guerrero-Bosagna et al., 2010; Ng et al., 2010; Dietz et al., 2011; Vassoler et al”
Epigenetics in Human Obesity and Type 2 Diabetes (2019, background): “There are also examples of paternal transmission of epigenetic information, where offspring to male mice on a high-fat diet display altered metabolic phenotypes, including obesity and b cell dysfunction, and gene expression in the pancreatic islet (Ng et al., 2010).”
The nature of nutrition: a unifying framework (2011, background): “Obesity in fathers can, it seems, also affect metabolic function in offspring (Ng et al. 2010).”
The Dynamics of Genome-wide DNA Methylation Reprogramming in Mouse Primordial Germ Cells (2012, background): “These CGIs may be candidates for short-term transgenerational inheritance in mammals, which seems variable in its persistence and hence heritability (Jimenez-Chillaron et al., 2009; Carone et al., 2010; Ng et al., 2010; Daxinger and Whitelaw, 2012).”
Understanding transgenerational epigenetic inheritance via the gametes in mammals (2012, background): “A recent study in rats has shown that when sires are fed a high-fat diet, female offspring show a subtle pancreatic phenotype as well as concomitant changes in the expression of some genes involved in insulin regulation and in glucose metabolism compared with those that are sired by males fed a norm”