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

Sheau-Fang Ng; Ruby C Y Lin; D Ross Laybutt; Romain Barres; Julie A Owens; Margaret J Morris

doi:10.1038/nature09491

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

Sheau-Fang Ng, Ruby C Y Lin, D Ross Laybutt, Romain Barres, Julie A Owens, Margaret J Morris

915 Citations (Scopus)

Abstract

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 2-cell "dysfunction" in rat F 1 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.

Original language	English
Journal	Nature
Volume	467
Issue number	7318
Pages (from-to)	963-6
Number of pages	4
DOIs	https://doi.org/10.1038/nature09491
Publication status	Published - 21 Oct 2010

Keywords

Adenosine Triphosphate
Adiposity
Aging
Animals
Apoptosis
Body Weight
Cations
Cell Cycle
Cytoskeleton
DNA Methylation
Diabetes Mellitus, Type 2
Diet
Dietary Fats
Epigenesis, Genetic
Fathers
Female
Gene Expression Profiling
Gene Expression Regulation
Glucose
Glucose Intolerance
Glucose Tolerance Test
Homeostasis
Insulin
Insulin-Secreting Cells
Litter Size
Male
Obesity
Paternal Exposure
Rats
Rats, Sprague-Dawley
Signal Transduction

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1038/nature09491

Cite this

@article{9cb973840d054ce79ba462b841868e26,

title = "Chronic high-fat diet in fathers programs {\ss}-cell dysfunction in female rat offspring",

abstract = "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 2-cell {"}dysfunction{"} in rat F 1 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.",

keywords = "Adenosine Triphosphate, Adiposity, Aging, Animals, Apoptosis, Body Weight, Cations, Cell Cycle, Cytoskeleton, DNA Methylation, Diabetes Mellitus, Type 2, Diet, Dietary Fats, Epigenesis, Genetic, Fathers, Female, Gene Expression Profiling, Gene Expression Regulation, Glucose, Glucose Intolerance, Glucose Tolerance Test, Homeostasis, Insulin, Insulin-Secreting Cells, Litter Size, Male, Obesity, Paternal Exposure, Rats, Rats, Sprague-Dawley, Signal Transduction",

author = "Sheau-Fang Ng and Lin, {Ruby C Y} and Laybutt, {D Ross} and Romain Barres and Owens, {Julie A} and Morris, {Margaret J}",

year = "2010",

month = oct,

day = "21",

doi = "10.1038/nature09491",

language = "English",

volume = "467",

pages = "963--6",

journal = "Nature",

issn = "1476-4687",

publisher = "nature publishing group",

number = "7318",

}

TY - JOUR

T1 - Chronic high-fat diet in fathers programs ß-cell dysfunction in female rat offspring

AU - Ng, Sheau-Fang

AU - Lin, Ruby C Y

AU - Laybutt, D Ross

AU - Barres, Romain

AU - Owens, Julie A

AU - Morris, Margaret J

PY - 2010/10/21

Y1 - 2010/10/21

N2 - 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 2-cell "dysfunction" in rat F 1 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.

AB - 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 2-cell "dysfunction" in rat F 1 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.

KW - Adenosine Triphosphate

KW - Adiposity

KW - Aging

KW - Animals

KW - Apoptosis

KW - Body Weight

KW - Cations

KW - Cell Cycle

KW - Cytoskeleton

KW - DNA Methylation

KW - Diabetes Mellitus, Type 2

KW - Diet

KW - Dietary Fats

KW - Epigenesis, Genetic

KW - Fathers

KW - Female

KW - Gene Expression Profiling

KW - Gene Expression Regulation

KW - Glucose

KW - Glucose Intolerance

KW - Glucose Tolerance Test

KW - Homeostasis

KW - Insulin

KW - Insulin-Secreting Cells

KW - Litter Size

KW - Male

KW - Obesity

KW - Paternal Exposure

KW - Rats

KW - Rats, Sprague-Dawley

KW - Signal Transduction

U2 - 10.1038/nature09491

DO - 10.1038/nature09491

M3 - Journal article

C2 - 20962845

SN - 1476-4687

VL - 467

SP - 963

EP - 966

JO - Nature

JF - Nature

IS - 7318

ER -

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

Abstract

Keywords

UN SDGs

Access to Document

Fingerprint

Cite this