Chronic high-fat diet in fathers programs β-cell dysfunction in female rat offspring
Paternal diet linked to glucose intolerance in daughters Childhood obesity and diabetes are closely related to these conditions in either parent, but how the father contributes is unclear. A study in rats shows that normal females mated with obese, glucose-intolerant fathers on a high-fat diet produ...
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| creator | Ng, Sheau-Fang Lin, Ruby C. Y. Laybutt, D. Ross Barres, Romain Owens, Julie A. Morris, Margaret J. |
| description | Paternal diet linked to glucose intolerance in daughters
Childhood obesity and diabetes are closely related to these conditions in either parent, but how the father contributes is unclear. A study in rats shows that normal females mated with obese, glucose-intolerant fathers on a high-fat diet produce female offspring who develop glucose intolerance due to impaired insulin secretion and pancreatic function. This is the first report in any species that a father's diet can initiate progression to diabetes in his offspring. The work highlights a novel role for environmentally induced paternal factors in influencing metabolic disease in offspring and in the growing epidemics of obesity and diabetes.
Here it is shown that the consumption of a high-fat diet by male rats has an intergenerational effect: it leads to the dysfunction of pancreatic β-cells in female offspring. Relative to controls, these offspring showed an early onset of impaired insulin secretion and glucose tolerance, which worsened with time. The results add to our understanding of the complex genetic and environmental factors that are leading to the global epidemic of obesity and type 2 diabetes.
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
1
,
2
. Having either parent obese is an independent risk factor for childhood obesity
3
. Although the detrimental impacts of diet-induced maternal obesity on adiposity and metabolism in offspring are well established
4
, 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 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
|
| doi_str_mv | 10.1038/nature09491 |
| format | Article |
| fullrecord | <record><control><sourceid>gale_proqu</sourceid><recordid>TN_cdi_proquest_miscellaneous_856767807</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A240579786</galeid><sourcerecordid>A240579786</sourcerecordid><originalsourceid>FETCH-LOGICAL-c483t-f84e15f2db28fcc242b8f93fa1baee18761bcb40394fad25ab39606191a78dac3</originalsourceid><addsrcrecordid>eNpt0l-L1DAQAPAgireePvkuxUNEtGfSpkn6eCz-OTgQ1HsO03TSzdGme0kL3tfyg_iZzNpVb2HJQ0L4zWTIDCHPGT1ntFTvPUxzQFrzmj0gK8alyLlQ8iFZUVqonKpSnJAnMd5QSism-WNyUtBaFIpXK3K93oTRO5NtXLfJLUxZ63DKnM_SeYMhZtswdgGGmP36mRvs-6y9i3b2ZnKj_-NwgB6zkEJHa-M2ON89JY8s9BGf7fdTcv3xw_f15_zqy6fL9cVVbrgqp9wqjqyyRdsUyhpT8KJRti4tsAYQmZKCNabhtKy5hbaooClrQQWrGUjVgilPyeslbyrydsY46cHFXZHgcZyjVpWQQioqkzxbZJeK1c7bcQpgdlpfFJxWspZKJJUfUR16DNCPHq1L1wf-5RFvtu5W30fnR1BaLQ7OHM365iAgmQl_TB3MMerLb18P7dvFmjDGGNDq1IABwp1mVO_GQ98bj6Rf7P9rbgZs_9m_85DAqz2AaKC3Abxx8b8rS5ZWndy7xS39xqBvxjn41Ouj7_4G3vLQMw</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>856767807</pqid></control><display><type>article</type><title>Chronic high-fat diet in fathers programs β-cell dysfunction in female rat offspring</title><source>MEDLINE</source><source>Springer Nature - Complete Springer Journals</source><source>Nature Journals Online</source><creator>Ng, Sheau-Fang ; Lin, Ruby C. Y. ; Laybutt, D. Ross ; Barres, Romain ; Owens, Julie A. ; Morris, Margaret J.</creator><creatorcontrib>Ng, Sheau-Fang ; Lin, Ruby C. Y. ; Laybutt, D. Ross ; Barres, Romain ; Owens, Julie A. ; Morris, Margaret J.</creatorcontrib><description>Paternal diet linked to glucose intolerance in daughters
Childhood obesity and diabetes are closely related to these conditions in either parent, but how the father contributes is unclear. A study in rats shows that normal females mated with obese, glucose-intolerant fathers on a high-fat diet produce female offspring who develop glucose intolerance due to impaired insulin secretion and pancreatic function. This is the first report in any species that a father's diet can initiate progression to diabetes in his offspring. The work highlights a novel role for environmentally induced paternal factors in influencing metabolic disease in offspring and in the growing epidemics of obesity and diabetes.
Here it is shown that the consumption of a high-fat diet by male rats has an intergenerational effect: it leads to the dysfunction of pancreatic β-cells in female offspring. Relative to controls, these offspring showed an early onset of impaired insulin secretion and glucose tolerance, which worsened with time. The results add to our understanding of the complex genetic and environmental factors that are leading to the global epidemic of obesity and type 2 diabetes.
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
1
,
2
. Having either parent obese is an independent risk factor for childhood obesity
3
. Although the detrimental impacts of diet-induced maternal obesity on adiposity and metabolism in offspring are well established
4
, 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 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.</description><identifier>ISSN: 0028-0836</identifier><identifier>EISSN: 1476-4687</identifier><identifier>DOI: 10.1038/nature09491</identifier><identifier>PMID: 20962845</identifier><identifier>CODEN: NATUAS</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>631/136 ; 631/443/319/1642/137/773 ; 631/443/319/1642/393 ; Abnormalities ; Adenosine Triphosphate - metabolism ; Adiposity - drug effects ; Aging - genetics ; Animals ; Apoptosis - genetics ; Biological and medical sciences ; Body Weight - drug effects ; Care and treatment ; Cations - metabolism ; Cell Cycle - genetics ; Cytoskeleton - metabolism ; Diabetes Mellitus, Type 2 - etiology ; Diabetes Mellitus, Type 2 - pathology ; Diabetes Mellitus, Type 2 - physiopathology ; Diabetes. Impaired glucose tolerance ; Diet - adverse effects ; Dietary Fats - administration & dosage ; Dietary Fats - adverse effects ; DNA Methylation - drug effects ; Endocrine pancreas. Apud cells (diseases) ; Endocrinopathies ; Epigenesis, Genetic - drug effects ; Etiopathogenesis. Screening. Investigations. Target tissue resistance ; Fathers ; Female ; Gene Expression Profiling ; Gene Expression Regulation ; Glucose - pharmacology ; Glucose Intolerance - etiology ; Glucose Intolerance - pathology ; Glucose Intolerance - physiopathology ; Glucose Tolerance Test ; Health aspects ; Homeostasis - drug effects ; Humanities and Social Sciences ; Insulin - metabolism ; Insulin Secretion ; Insulin-Secreting Cells - metabolism ; Insulin-Secreting Cells - pathology ; letter ; Litter Size ; Male ; Medical sciences ; Metabolic diseases ; multidisciplinary ; Obesity ; Obesity - etiology ; Obesity - pathology ; Obesity - physiopathology ; Obesity in children ; Pancreatic beta cells ; Paternal Exposure - adverse effects ; Physiological aspects ; Rats ; Rats, Sprague-Dawley ; Risk factors ; Science ; Science (multidisciplinary) ; Signal Transduction - genetics</subject><ispartof>Nature (London), 2010-10, Vol.467 (7318), p.963-966</ispartof><rights>Springer Nature Limited 2010</rights><rights>2015 INIST-CNRS</rights><rights>COPYRIGHT 2010 Nature Publishing Group</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c483t-f84e15f2db28fcc242b8f93fa1baee18761bcb40394fad25ab39606191a78dac3</citedby><cites>FETCH-LOGICAL-c483t-f84e15f2db28fcc242b8f93fa1baee18761bcb40394fad25ab39606191a78dac3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1038/nature09491$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1038/nature09491$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,778,782,27913,27914,41477,42546,51308</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=23313139$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/20962845$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ng, Sheau-Fang</creatorcontrib><creatorcontrib>Lin, Ruby C. Y.</creatorcontrib><creatorcontrib>Laybutt, D. Ross</creatorcontrib><creatorcontrib>Barres, Romain</creatorcontrib><creatorcontrib>Owens, Julie A.</creatorcontrib><creatorcontrib>Morris, Margaret J.</creatorcontrib><title>Chronic high-fat diet in fathers programs β-cell dysfunction in female rat offspring</title><title>Nature (London)</title><addtitle>Nature</addtitle><addtitle>Nature</addtitle><description>Paternal diet linked to glucose intolerance in daughters
Childhood obesity and diabetes are closely related to these conditions in either parent, but how the father contributes is unclear. A study in rats shows that normal females mated with obese, glucose-intolerant fathers on a high-fat diet produce female offspring who develop glucose intolerance due to impaired insulin secretion and pancreatic function. This is the first report in any species that a father's diet can initiate progression to diabetes in his offspring. The work highlights a novel role for environmentally induced paternal factors in influencing metabolic disease in offspring and in the growing epidemics of obesity and diabetes.
Here it is shown that the consumption of a high-fat diet by male rats has an intergenerational effect: it leads to the dysfunction of pancreatic β-cells in female offspring. Relative to controls, these offspring showed an early onset of impaired insulin secretion and glucose tolerance, which worsened with time. The results add to our understanding of the complex genetic and environmental factors that are leading to the global epidemic of obesity and type 2 diabetes.
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
1
,
2
. Having either parent obese is an independent risk factor for childhood obesity
3
. Although the detrimental impacts of diet-induced maternal obesity on adiposity and metabolism in offspring are well established
4
, 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 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.</description><subject>631/136</subject><subject>631/443/319/1642/137/773</subject><subject>631/443/319/1642/393</subject><subject>Abnormalities</subject><subject>Adenosine Triphosphate - metabolism</subject><subject>Adiposity - drug effects</subject><subject>Aging - genetics</subject><subject>Animals</subject><subject>Apoptosis - genetics</subject><subject>Biological and medical sciences</subject><subject>Body Weight - drug effects</subject><subject>Care and treatment</subject><subject>Cations - metabolism</subject><subject>Cell Cycle - genetics</subject><subject>Cytoskeleton - metabolism</subject><subject>Diabetes Mellitus, Type 2 - etiology</subject><subject>Diabetes Mellitus, Type 2 - pathology</subject><subject>Diabetes Mellitus, Type 2 - physiopathology</subject><subject>Diabetes. Impaired glucose tolerance</subject><subject>Diet - adverse effects</subject><subject>Dietary Fats - administration & dosage</subject><subject>Dietary Fats - adverse effects</subject><subject>DNA Methylation - drug effects</subject><subject>Endocrine pancreas. Apud cells (diseases)</subject><subject>Endocrinopathies</subject><subject>Epigenesis, Genetic - drug effects</subject><subject>Etiopathogenesis. Screening. Investigations. Target tissue resistance</subject><subject>Fathers</subject><subject>Female</subject><subject>Gene Expression Profiling</subject><subject>Gene Expression Regulation</subject><subject>Glucose - pharmacology</subject><subject>Glucose Intolerance - etiology</subject><subject>Glucose Intolerance - pathology</subject><subject>Glucose Intolerance - physiopathology</subject><subject>Glucose Tolerance Test</subject><subject>Health aspects</subject><subject>Homeostasis - drug effects</subject><subject>Humanities and Social Sciences</subject><subject>Insulin - metabolism</subject><subject>Insulin Secretion</subject><subject>Insulin-Secreting Cells - metabolism</subject><subject>Insulin-Secreting Cells - pathology</subject><subject>letter</subject><subject>Litter Size</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Metabolic diseases</subject><subject>multidisciplinary</subject><subject>Obesity</subject><subject>Obesity - etiology</subject><subject>Obesity - pathology</subject><subject>Obesity - physiopathology</subject><subject>Obesity in children</subject><subject>Pancreatic beta cells</subject><subject>Paternal Exposure - adverse effects</subject><subject>Physiological aspects</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Risk factors</subject><subject>Science</subject><subject>Science (multidisciplinary)</subject><subject>Signal Transduction - genetics</subject><issn>0028-0836</issn><issn>1476-4687</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpt0l-L1DAQAPAgireePvkuxUNEtGfSpkn6eCz-OTgQ1HsO03TSzdGme0kL3tfyg_iZzNpVb2HJQ0L4zWTIDCHPGT1ntFTvPUxzQFrzmj0gK8alyLlQ8iFZUVqonKpSnJAnMd5QSism-WNyUtBaFIpXK3K93oTRO5NtXLfJLUxZ63DKnM_SeYMhZtswdgGGmP36mRvs-6y9i3b2ZnKj_-NwgB6zkEJHa-M2ON89JY8s9BGf7fdTcv3xw_f15_zqy6fL9cVVbrgqp9wqjqyyRdsUyhpT8KJRti4tsAYQmZKCNabhtKy5hbaooClrQQWrGUjVgilPyeslbyrydsY46cHFXZHgcZyjVpWQQioqkzxbZJeK1c7bcQpgdlpfFJxWspZKJJUfUR16DNCPHq1L1wf-5RFvtu5W30fnR1BaLQ7OHM365iAgmQl_TB3MMerLb18P7dvFmjDGGNDq1IABwp1mVO_GQ98bj6Rf7P9rbgZs_9m_85DAqz2AaKC3Abxx8b8rS5ZWndy7xS39xqBvxjn41Ouj7_4G3vLQMw</recordid><startdate>20101021</startdate><enddate>20101021</enddate><creator>Ng, Sheau-Fang</creator><creator>Lin, Ruby C. Y.</creator><creator>Laybutt, D. Ross</creator><creator>Barres, Romain</creator><creator>Owens, Julie A.</creator><creator>Morris, Margaret J.</creator><general>Nature Publishing Group UK</general><general>Nature Publishing Group</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QH</scope><scope>7UA</scope><scope>C1K</scope></search><sort><creationdate>20101021</creationdate><title>Chronic high-fat diet in fathers programs β-cell dysfunction in female rat offspring</title><author>Ng, Sheau-Fang ; Lin, Ruby C. Y. ; Laybutt, D. Ross ; Barres, Romain ; Owens, Julie A. ; Morris, Margaret J.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c483t-f84e15f2db28fcc242b8f93fa1baee18761bcb40394fad25ab39606191a78dac3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2010</creationdate><topic>631/136</topic><topic>631/443/319/1642/137/773</topic><topic>631/443/319/1642/393</topic><topic>Abnormalities</topic><topic>Adenosine Triphosphate - metabolism</topic><topic>Adiposity - drug effects</topic><topic>Aging - genetics</topic><topic>Animals</topic><topic>Apoptosis - genetics</topic><topic>Biological and medical sciences</topic><topic>Body Weight - drug effects</topic><topic>Care and treatment</topic><topic>Cations - metabolism</topic><topic>Cell Cycle - genetics</topic><topic>Cytoskeleton - metabolism</topic><topic>Diabetes Mellitus, Type 2 - etiology</topic><topic>Diabetes Mellitus, Type 2 - pathology</topic><topic>Diabetes Mellitus, Type 2 - physiopathology</topic><topic>Diabetes. Impaired glucose tolerance</topic><topic>Diet - adverse effects</topic><topic>Dietary Fats - administration & dosage</topic><topic>Dietary Fats - adverse effects</topic><topic>DNA Methylation - drug effects</topic><topic>Endocrine pancreas. Apud cells (diseases)</topic><topic>Endocrinopathies</topic><topic>Epigenesis, Genetic - drug effects</topic><topic>Etiopathogenesis. Screening. Investigations. Target tissue resistance</topic><topic>Fathers</topic><topic>Female</topic><topic>Gene Expression Profiling</topic><topic>Gene Expression Regulation</topic><topic>Glucose - pharmacology</topic><topic>Glucose Intolerance - etiology</topic><topic>Glucose Intolerance - pathology</topic><topic>Glucose Intolerance - physiopathology</topic><topic>Glucose Tolerance Test</topic><topic>Health aspects</topic><topic>Homeostasis - drug effects</topic><topic>Humanities and Social Sciences</topic><topic>Insulin - metabolism</topic><topic>Insulin Secretion</topic><topic>Insulin-Secreting Cells - metabolism</topic><topic>Insulin-Secreting Cells - pathology</topic><topic>letter</topic><topic>Litter Size</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Metabolic diseases</topic><topic>multidisciplinary</topic><topic>Obesity</topic><topic>Obesity - etiology</topic><topic>Obesity - pathology</topic><topic>Obesity - physiopathology</topic><topic>Obesity in children</topic><topic>Pancreatic beta cells</topic><topic>Paternal Exposure - adverse effects</topic><topic>Physiological aspects</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>Risk factors</topic><topic>Science</topic><topic>Science (multidisciplinary)</topic><topic>Signal Transduction - genetics</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ng, Sheau-Fang</creatorcontrib><creatorcontrib>Lin, Ruby C. Y.</creatorcontrib><creatorcontrib>Laybutt, D. Ross</creatorcontrib><creatorcontrib>Barres, Romain</creatorcontrib><creatorcontrib>Owens, Julie A.</creatorcontrib><creatorcontrib>Morris, Margaret J.</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Aqualine</collection><collection>Water Resources Abstracts</collection><collection>Environmental Sciences and Pollution Management</collection><jtitle>Nature (London)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ng, Sheau-Fang</au><au>Lin, Ruby C. Y.</au><au>Laybutt, D. Ross</au><au>Barres, Romain</au><au>Owens, Julie A.</au><au>Morris, Margaret J.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Chronic high-fat diet in fathers programs β-cell dysfunction in female rat offspring</atitle><jtitle>Nature (London)</jtitle><stitle>Nature</stitle><addtitle>Nature</addtitle><date>2010-10-21</date><risdate>2010</risdate><volume>467</volume><issue>7318</issue><spage>963</spage><epage>966</epage><pages>963-966</pages><issn>0028-0836</issn><eissn>1476-4687</eissn><coden>NATUAS</coden><abstract>Paternal diet linked to glucose intolerance in daughters
Childhood obesity and diabetes are closely related to these conditions in either parent, but how the father contributes is unclear. A study in rats shows that normal females mated with obese, glucose-intolerant fathers on a high-fat diet produce female offspring who develop glucose intolerance due to impaired insulin secretion and pancreatic function. This is the first report in any species that a father's diet can initiate progression to diabetes in his offspring. The work highlights a novel role for environmentally induced paternal factors in influencing metabolic disease in offspring and in the growing epidemics of obesity and diabetes.
Here it is shown that the consumption of a high-fat diet by male rats has an intergenerational effect: it leads to the dysfunction of pancreatic β-cells in female offspring. Relative to controls, these offspring showed an early onset of impaired insulin secretion and glucose tolerance, which worsened with time. The results add to our understanding of the complex genetic and environmental factors that are leading to the global epidemic of obesity and type 2 diabetes.
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
1
,
2
. Having either parent obese is an independent risk factor for childhood obesity
3
. Although the detrimental impacts of diet-induced maternal obesity on adiposity and metabolism in offspring are well established
4
, 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 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.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>20962845</pmid><doi>10.1038/nature09491</doi><tpages>4</tpages></addata></record> |
| fulltext | fulltext |
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| ispartof | Nature (London), 2010-10, Vol.467 (7318), p.963-966 |
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| source | MEDLINE; Springer Nature - Complete Springer Journals; Nature Journals Online |
| subjects | 631/136 631/443/319/1642/137/773 631/443/319/1642/393 Abnormalities Adenosine Triphosphate - metabolism Adiposity - drug effects Aging - genetics Animals Apoptosis - genetics Biological and medical sciences Body Weight - drug effects Care and treatment Cations - metabolism Cell Cycle - genetics Cytoskeleton - metabolism Diabetes Mellitus, Type 2 - etiology Diabetes Mellitus, Type 2 - pathology Diabetes Mellitus, Type 2 - physiopathology Diabetes. Impaired glucose tolerance Diet - adverse effects Dietary Fats - administration & dosage Dietary Fats - adverse effects DNA Methylation - drug effects Endocrine pancreas. Apud cells (diseases) Endocrinopathies Epigenesis, Genetic - drug effects Etiopathogenesis. Screening. Investigations. Target tissue resistance Fathers Female Gene Expression Profiling Gene Expression Regulation Glucose - pharmacology Glucose Intolerance - etiology Glucose Intolerance - pathology Glucose Intolerance - physiopathology Glucose Tolerance Test Health aspects Homeostasis - drug effects Humanities and Social Sciences Insulin - metabolism Insulin Secretion Insulin-Secreting Cells - metabolism Insulin-Secreting Cells - pathology letter Litter Size Male Medical sciences Metabolic diseases multidisciplinary Obesity Obesity - etiology Obesity - pathology Obesity - physiopathology Obesity in children Pancreatic beta cells Paternal Exposure - adverse effects Physiological aspects Rats Rats, Sprague-Dawley Risk factors Science Science (multidisciplinary) Signal Transduction - genetics |
| title | Chronic high-fat diet in fathers programs β-cell dysfunction in female rat offspring |
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