Epigenetic Germline Inheritance of Diet-Induced Obesity and Insulin Resistance

Huypens, Peter; Sass, Steffen; Wu, Moya; Dyckhoff, Daniela; Tschöp, Matthias H.; Tc, Fabian; Marschall, Susan; Angelis, Martin Hrabé de; Beckers, Johannes

doi:10.1097/01.ogx.0000511202.23878.e3

Cited by 28 publications

(42 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…However, Masuyama et al reported no difference in body weight from 4 to 16 weeks of age, followed by increased body weight and homeostatic model assessment of insulin resistance at 24 weeks of age in male offspring from fathers fed a 62% fat diet . Moreover, using in vitro fertilization, Huypens et al found that sperm isolated from F0 mice fed a 60% fat diet did not induce changes in body weight or glucose tolerance in male offspring at 14 weeks of age . In our study, using a mouse model of paternal obesity induced by a 60% fat diet, we also found no differences in body weight or blood metabolic parameters in male offspring at 8 weeks of age.…”

Section: Discussionsupporting

confidence: 59%

“…However, there are differential effects of paternal obesity on offspring phenotype across different mouse models. For example, Fullston et al showed that paternal exposure to a 40% fat diet increased body weight and impaired glucose tolerance in male offspring from 8 weeks of age onward (33 (35). In our study, using a mouse model of paternal obesity induced by a 60% fat diet, we also found no differences in body weight or blood metabolic parameters in male offspring at 8 weeks of age.…”

Section: Discussionsupporting

confidence: 55%

See 1 more Smart Citation

Diet‐Induced Paternal Obesity Impairs Cognitive Function in Offspring by Mediating Epigenetic Modifications in Spermatozoa

Zhou

Zhu

et al. 2018

Obesity

View full text Add to dashboard Cite

Objective This study aimed to determine the effects of diet‐induced paternal obesity on cognitive function in mice offspring. Methods Male mice (F0) were randomized to receive either a control diet (10 kcal% fat) or a high‐fat diet (HFD; 60 kcal% fat) for 10 weeks before being mated with normal females to generate F1 offspring. Male F1 offspring were mated with normal females to generate F2 offspring. Behavioral tests were used to assess cognitive functions in F1 and F2 offspring. Reduced representation bisulfite sequencing was used to the explore mechanisms of epigenetic inheritance. Results HFD‐induced paternal obesity resulted in cognitive impairments in F1 offspring, potentially due, at least in part, to increased methylation of the BDNF gene promoter, which was inherited from F0 spermatozoa. BDNF/tyrosine receptor kinase B signaling was associated with cognitive impairments in HFD‐fed F1 offspring. However, there were no significant changes in F2 offspring. Conclusions The findings provide evidence of intergenerational effects of paternal obesity on cognitive function in offspring occurring via epigenetic spermatozoan modifications.

show abstract

Section: Discussionsupporting

confidence: 59%

Section: Discussionsupporting

confidence: 55%

Diet‐Induced Paternal Obesity Impairs Cognitive Function in Offspring by Mediating Epigenetic Modifications in Spermatozoa

Zhou

Zhu

et al. 2018

Obesity

View full text Add to dashboard Cite

show abstract

“…Unfortunately, it found no association between paternal obesity and risk of CP in children . However, recent studies have found that a parental high‐fat diet mouse model renders offspring more susceptible to developing diabetes and obesity in a sex and parent of origin–specific mode by using in vitro fertilization to ensure exclusive inheritance via the gametes . Therefore, paternal obesity should be an important confounding factor for the risk of CP in children with obese mothers.…”

Section: Discussionmentioning

confidence: 99%

Maternal obesity and risk of cerebral palsy in children: a systematic review and meta‐analysis

Zhang

Peng

Chang

et al. 2018

Develop Med Child Neuro

View full text Add to dashboard Cite

show abstract

“…We previously found specific perturbations relating to fertilization, blastocyst formation, and implantation using our published mouse model of paternal obesity, which was achieved through diet‐induced obesity in males (Bakos, Mitchell, Setchell, & Lane, ; Mitchell, Bakos, & Lane, ; Binder, Mitchell, & Gardner, ; McPherson, Bakos, Owens, Setchell, & Lane, ). Importantly, our mouse model transmitted aberrant glucose metabolism as well as adiposity to the F1 and F2 generations (Fullston et al, , ); this generation‐spanning phenotype was recently confirmed in a mouse model using in vitro fertilization (Huypens et al, ). These data together support the hypothesis that aberrant regulation of factors controlling gene expression—including epigenetic deregulation—is initiated during spermatogenesis.…”

Section: Introductionmentioning

confidence: 54%

Gene expression and epigenetic aberrations in F1‐placentas fathered by obese males

Mitchell

Strick

Strissel

et al. 2017

Molecular Reproduction Devel

View full text Add to dashboard Cite

Gene expression and/or epigenetic deregulation may have consequences for sperm and blastocysts, as well as for the placenta, together potentially contributing to problems observed in offspring. We previously demonstrated specific perturbations of fertilization, blastocyst formation, implantation, as well as aberrant glucose metabolism and adiposity in offspring using a mouse model of paternal obesity. The current investigation analyzed gene expression and methylation of specific CpG residues in F1 placentas of pregnancies fathered by obese and normal-weight male mice, using real-time PCR and bisulfite pyrosequencing. Our aim was to determine if paternal obesity deregulated placental gene expression and DNA methylation when compared to normal-weight males. Gene methylation of sperm DNA was analyzed and compared to placentas to address epigenetic transmission. Of the 10 paternally expressed genes (Pegs), 11 genes important for development and transport of nutrients, and the long-terminal repeat Intracisternal A particle (IAP) elements, derived from a member of the class II endogenous retroviral gene family, we observed a significant effect of paternal diet-induced obesity on deregulated expression of Peg3, Peg9, Peg10, and the nutrient transporter gene Slc38a2, and aberrant DNA methylation of the Peg9 promoter in F1 placental tissue. Epigenetic changes in Peg9 were also found in sperm from obese fathers. We therefore propose that paternal obesity renders changes in gene expression and/or methylation throughout the placental genome, which could contribute to the reproductive problems related to fertility and to the metabolic, long-term health impact on offspring.

show abstract

Epigenetic Germline Inheritance of Diet-Induced Obesity and Insulin Resistance

Abstract: (Abstracted from Nat Genet 2016;48:497–499) Several genetic risk factors for diabetes and obesity have been identified. In addition to genetic risk factors, it has been proposed that epigenetic alterations in gametes are another potential mechanism of disease risk inheritance.

Cited by 28 publications

References 0 publications

Diet‐Induced Paternal Obesity Impairs Cognitive Function in Offspring by Mediating Epigenetic Modifications in Spermatozoa

Diet‐Induced Paternal Obesity Impairs Cognitive Function in Offspring by Mediating Epigenetic Modifications in Spermatozoa

Maternal obesity and risk of cerebral palsy in children: a systematic review and meta‐analysis

Gene expression and epigenetic aberrations in F1‐placentas fathered by obese males

Contact Info

Product

Resources

About