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Chronic high-fat diet in fathers programs β-cell dysfunction in female rat offspring
Sheau-Fang Ng1, Ruby C Y Lin, D Ross Laybutt
1Department of Pharmacology, School of Medical Sciences, University of New South Wales, New South Wales, Sydney 2052, Australia.
Nature
|October 22, 2010
Summary
Paternal high-fat diet exposure in rats programs metabolic dysfunction in female offspring, impacting insulin secretion and glucose tolerance. This study reveals non-genetic intergenerational effects from fathers to offspring.
Area of Science:
- Metabolic Research
- Reproductive Biology
- Genetics and Epigenetics
Background:
- Global obesity rates are rising, contributing to type 2 diabetes. Parental obesity is a risk factor for childhood obesity.
- Maternal obesity's impact on offspring is known, but paternal effects, especially non-genetic ones, are less understood.
- Investigating paternal diet's role in intergenerational metabolic programming is crucial for understanding obesity and diabetes transmission.
Purpose of the Study:
- To investigate the non-genetic effects of paternal high-fat diet (HFD) exposure on the metabolic health of offspring.
- To determine if paternal HFD can induce metabolic dysfunction, specifically β-cell dysfunction, in female offspring.
- To explore the molecular mechanisms, including gene expression and epigenetic changes, underlying paternal HFD-induced metabolic programming in offspring.
Main Methods:
- Sprague-Dawley rats were fed a high-fat diet (HFD) or control diet. Paternal HFD exposure was maintained chronically before mating.
- Female offspring (F1 generation) were assessed for metabolic parameters including body weight, adiposity, glucose tolerance, and insulin sensitivity.
- Pancreatic islet gene expression, broader gene pathways, and specific gene methylation (Il13ra2) were analyzed in adult female offspring.
Main Results:
- Paternal HFD induced obesity, impaired glucose tolerance, and insulin resistance in fathers.
- Female offspring exhibited early-onset impaired insulin secretion and glucose tolerance, worsening over time, despite normal adiposity.
- Paternal HFD altered expression of 642 pancreatic islet genes and 2,492 broader genes in offspring, involving signaling pathways (calcium, MAPK, Wnt) and epigenetic changes like Il13ra2 hypomethylation.
Conclusions:
- Paternal HFD exposure can program β-cell dysfunction and metabolic disturbances in female offspring through non-genetic, intergenerational transmission.
- This study provides the first evidence in mammals of metabolic consequences of paternal HFD being passed to offspring without genetic changes.
- Findings highlight the critical role of paternal metabolic health and diet in offspring's long-term metabolic programming and disease risk.
