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Pregnancy Timeline by SemestersDevelopmental TimelineFertilizationFirst TrimesterSecond TrimesterThird TrimesterFirst Thin Layer of Skin AppearsEnd of Embryonic PeriodEnd of Embryonic PeriodFemale Reproductive SystemBeginning Cerebral HemispheresA Four Chambered HeartFirst Detectable Brain WavesThe Appearance of SomitesBasic Brain Structure in PlaceHeartbeat can be detectedHeartbeat can be detectedFinger and toe prints appearFinger and toe prints appearFetal sexual organs visibleBrown fat surrounds lymphatic systemBone marrow starts making blood cellsBone marrow starts making blood cellsInner Ear Bones HardenSensory brain waves begin to activateSensory brain waves begin to activateFetal liver is producing blood cellsBrain convolutions beginBrain convolutions beginImmune system beginningWhite fat begins to be madeHead may position into pelvisWhite fat begins to be madePeriod of rapid brain growthFull TermHead may position into pelvisImmune system beginningLungs begin to produce surfactant
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Developmental biology - Genes

Dangerous Fat Comes From Dad - Good Fat From Mom

The gene H19 protects against overweight and could affect diabetes and cardiovascular disease...


A new function has been discovered for the gene H19. It turns out to have a unique protective effect against becoming overweight and could affect the onset of excess weight associated with cardiovascular diseases and diabetes.

Making a groundbreaking discovery in obesity research are a team led by Jan-Wilhelm Kornfeld PhD, from the Department of Biochemistry and Molecular Biology, at the University of Southern Denmark; Elena Schmidt from the Max Planck Institute for Metabolism Research, Cologne, Germany; and Martin Bilban from the Medial University in Vienna, Austria.
H19 belongs to the one percent of our genes, which we inherit exclusively from either our mother or father, our monoallelic genes.

After extensive study, researchers found H19 monoallelic genes derived from our father primarily lead to the development of white fat tissue, most often found on our stomach, thighs and backside, which can lead to metabolic diseases.

Likewise, it appears H19 monoallelic genes from our mother primarily lead to the development of brown fat tissue, characterized as having a protective effect against obesity.

Professors Jan-Wilhelm Kornfeld and Martin Bilban are delighted to have these results as they constitute a first step towards development of better treatments for obesity.

Using mouse models, the team identified how overexpression of H19 controls brown fat cells, protecting against obesity and insulin resistance. They also detected similar patterns of H19 gene control in obese humans. Professor Jan-Wilhelm Kornfeld hopes these results will be the first steps to developing new and improved treatments for obesity-related diseases.

The work is published in the journal Nature Communications.

Abstract
Increasing brown adipose tissue (BAT) thermogenesis in mice and humans improves metabolic health and understanding BAT function is of interest for novel approaches to counteract obesity. The role of long noncoding RNAs (lncRNAs) in these processes remains elusive. We observed maternally expressed, imprinted lncRNA H19 increased upon cold-activation and decreased in obesity in BAT. Inverse correlations of H19 with BMI were also observed in humans. H19 overexpression promoted, while silencing of H19 impaired adipogenesis, oxidative metabolism and mitochondrial respiration in brown but not white adipocytes. In vivo, H19 overexpression protected against DIO, improved insulin sensitivity and mitochondrial biogenesis, whereas fat H19 loss sensitized towards HFD weight gains. Strikingly, paternally expressed genes (PEG) were largely absent from BAT and we demonstrated that H19 recruits PEG-inactivating H19-MBD1 complexes and acts as BAT-selective PEG gatekeeper. This has implications for our understanding how monoallelic gene expression affects metabolism in rodents and, potentially, humans.

Authors
Elena Schmidt, Ines Dhaouadi, Isabella Gaziano, Matteo Oliverio, Paul Klemm, Motoharu Awazawa, Gerfried Mitterer, Eduardo Fernandez-Rebollo, Marta Pradas-Juni, Wolfgang Wagner, Philipp Hammerschmidt, Rute Loureiro, Christoph Kiefer, Nils R. Hansmeier, Sajjad Khani, Matteo Bergami, Markus Heine, Evgenia Ntini, Peter Frommolt, Peter Zentis, Ulf Andersson Ørom, Jörg Heeren, Matthias Blüher, Martin Bilban and Jan-Wilhelm Kornfeld.


Funding
Jan-Wilhelm Kornfeld's research is supported by the Danish Diabetes Academy, founded by the Novo Nordisk Foundation.

We thank Christiane Schäfer and Pia Scholl for HE stainings and Beatrix Martiny for electron microscopy and Julia Husa and Markus Jeitler for help with cell culture and RNA-Seq. We acknowledge Jens Alber for technical assistance. Jenny Blommer determined TG and total cholesterole levels. Linheng Li from the Stowers Institute provided H19-DMRflDMR/flDMR mice. We thank Christian Frese, Brigitte Kisters-Woike, and Corinna Klein from CECAD Proteomics Core Facility. J.W.K., E.S., I.G., N.H., S.K., and M.O. are supported by the Emmy-Noether Program of the Deutsche Forschungsgemeinschaft (DFG; KO4728/1.1). J-W.K. receives funding from University of Southern Denmark (SDU) and Danish Diabetes Academy (DDA), which is funded by Novo Nordisk Fonden (NNF). M.P.J is grateful for support by CECAD. R.L., E.F-R., M.P.J., and P.K. receive support from the European Research Council (ERC) Starting Grant TransGenRNA (No. 675014). E.S. is supported by Evangelisches Studienwerk Villigst. S.K appreciates support from DAAD. N.R.H. received a stipend from the Cologne Graduate School for Ageing (CGA). E.N. was supported by an Alexander-von-Humboldt postdoctoral fellowship. This work was supported by the DFG, Obesity Mechanisms (SFB 1052, B01) to M.B.


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Sep 10, 2018   Fetal Timeline   Maternal Timeline   News   News Archive

A father's contribution to body fat is on the stomach, thighs and backside. While the mother
contributes brown fat and an ongoing metabolic fight against obesity. Photo: public domain.


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