Journal ArticleDOI
Paternal obesity initiates metabolic disturbances in two generations of mice with incomplete penetrance to the F2 generation and alters the transcriptional profile of testis and sperm microRNA content
Tod Fullston,E. Maria C. Ohlsson Teague,Nicole O. Palmer,Miles J. DeBlasio,Megan Mitchell,Mark A. Corbett,Cristin G. Print,Julie A. Owens,Michelle Lane +8 more
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TLDR
Diet‐induced paternal obesity modulates sperm microRNA content and germ cell methylation status, which are potential signals that program offspring health and initiate the transmission of obesity and impaired metabolic health to future generations.Abstract:
Obesity is highly prevalent, and its incidence is increasing. The previous study showing a major effect of paternal obesity on metabolic health of offspring is confounded by comorbidity with diabetes. Therefore, we investigated the effect of diet-induced paternal obesity, in the absence of diabetes, on the metabolic health of two resultant generations and the molecular profiles of the testes and sperm. Founder (F0) male C57BL6 mice were fed either a high-fat diet (HFD) or a control diet (CD); n = 10/diet for a period of 10 wk. Testis expression of mRNA/microRNAs was analyzed by microarray and qPCR and sperm microRNA abundance by qPCR. Two subsequent generations were generated by mating F0 and then F1 mice to CD mice, and their metabolic health was investigated. All mice, other than F0 males, were maintained on a CD. HFD feeding induced paternal obesity with a 21% increase in adiposity, but not overt diabetes, and initiated intergenerational transmission of obesity and insulin resistance in two generations of offspring. This distinct phenotypic constellation is either partially or fully transmitted to both female and male F1 offspring and further transmitted through both parental lineages to the F2 generation, with a heightened effect on female F1 offspring (+67% in adiposity) and their F2 sons (+24% in adiposity). Founder male obesity altered the testes expression of 414 mRNAs by microarray and 11 microRNAs by qPCR, concomitant with alterations in sperm microRNA content and a 25% reduction in global methylation of germ cell DNA. Diet-induced paternal obesity modulates sperm microRNA content and germ cell methylation status, which are potential signals that program offspring health and initiate the transmission of obesity and impaired metabolic health to future generations. This study implicates paternal obesity in the transgenerational amplification of obesity and type 2 diabetes in humans.read more
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Journal ArticleDOI
Sperm tsRNAs contribute to intergenerational inheritance of an acquired metabolic disorder
Qi Chen,Qi Chen,Menghong Yan,Zhonghong Cao,Xin Li,Yunfang Zhang,Junchao Shi,Guihai Feng,Hongying Peng,Hongying Peng,Xudong Zhang,Ying Zhang,Jingjing Qian,Enkui Duan,Qiwei Zhai,Qi Zhou +15 more
TL;DR: In a paternal mouse model given a high-fat diet, a subset of sperm transfer RNA–derived small RNAs (tsRNAs), mainly from 5′ transfer RNA halves and ranging in size from 30 to 34 nucleotides, exhibited changes in expression profiles and RNA modifications.
Journal ArticleDOI
Origins of lifetime health around the time of conception: causes and consequences.
Tom P. Fleming,Adam J. Watkins,Miguel A. Velazquez,John C. Mathers,Andrew M. Prentice,Judith Stephenson,Mary Barker,Mary Barker,Richard Saffery,Chittaranjan S. Yajnik,Judith J. Eckert,Mark A. Hanson,Mark A. Hanson,Terrence Forrester,Peter D. Gluckman,Peter D. Gluckman,Keith M. Godfrey,Keith M. Godfrey +17 more
TL;DR: It is proposed that the evidence for periconceptional effects on lifetime health is now so compelling that it calls for new guidance on parental preparation for pregnancy, beginning before conception, to protect the health of offspring.
Journal ArticleDOI
Transgenerational epigenetic programming via sperm microRNA recapitulates effects of paternal stress
TL;DR: Sperm miRs function to reduce maternal mRNA stores in early zygotes, ultimately reprogramming gene expression in the offspring hypothalamus and recapitulating the offspring stress dysregulation phenotype, demonstrating a clear mechanistic role in the transgenerational transmission of paternal lifetime experiences.
Journal ArticleDOI
Animal models of obesity and diabetes mellitus
Maximilian Kleinert,Christoffer Clemmensen,Susanna M. Hofmann,Mary Courtney Moore,Simone Renner,Stephen C. Woods,Peter Huypens,Johannes Beckers,Martin Hrabé de Angelis,Annette Schürmann,Mostafa Bakhti,Martin Klingenspor,Mark L. Heiman,Alan D. Cherrington,Michael Ristow,Heiko Lickert,Eckhard Wolf,Peter J. Havel,Timo D. Müller,Matthias H. Tschöp +19 more
TL;DR: This Review consolidates the key information on the currently available animal models of obesity and diabetes and highlights the advantages, limitations and important caveats of each of these models.
Journal ArticleDOI
Obesity Pathogenesis: An Endocrine Society Scientific Statement
Michael W. Schwartz,Randy J. Seeley,Lori M. Zeltser,Adam Drewnowski,Eric Ravussin,Leanne M. Redman,Rudolph L. Leibel +6 more
TL;DR: The scientific goal is to elucidate obesity pathogenesis so as to better inform treatment, public policy, advocacy, and awareness of obesity in ways that ultimately diminish its public health and economic consequences.
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