biostudies-literatureCimino Ithe Medical Research CouncilBritish Heart FoundationBHF programme grantMetabolic Disease UnitMedical Research CouncilNational Institute for Health Research (NIHR)Wellcome Trust17571https://www.ebi.ac.uk/biostudies/studies/S-EPMC8413370biostudies-literatureUnknown11(1)Neuronatin (Nnat) has previously been reported to be part of a network of imprinted genes downstream of the chromatin regulator Trim28. Disruption of Trim28 or of members of this network, including neuronatin, results in an unusual phenotype of a bimodal body weight. To better characterise this variability, we examined the key contributors to energy balance in Nnat^+/-p mice that carry a paternal null allele and do not express Nnat. Consistent with our previous studies, Nnat deficient mice on chow diet displayed a bimodal body weight phenotype with more than 30% of Nnat^+/-p mice developing obesity. In response to both a 45% high fat diet and exposure to thermoneutrality (30 °C) Nnat deficient mice maintained the hypervariable body weight phenotype. Within a calorimetryScientific reportsMurine neuronatin deficiency is associated with a hypervariable food intake and bimodal obesity.PMC8413370MC_UU_00014/1NF-SI-0616-10065RG/12/13/29853220271/Z/20/ZRG_18_7_33636MRC_MC_UU_00014/5G0400192MC_UU_12012/5MC_UU_12012/3G0802051MC_UU_12012/2MC_UU_12012/1MC_UU_12012/5/B207462/Z/17/ZRG/18/7/33636MC_UU_00014/5MC_G0802535MC_UU_00014/3208363/Z/17/ZMC_UU_00014/2100574/Z/12/ZGribble FMLarraufie PVidal-Puig ALawler KLam BYHMa MKLReimann FSaudek VVirtue SPospisilik JAColl APTung YCLYeo GSHRimmington DZvetkova ICimino IFagnocchi LFarooqi ISKay RGO'Rahilly SfalseMurine neuronatin deficiency is associated with a hypervariable food intake and bimodal obesity.Neuronatin (Nnat) has previously been reported to be part of a network of imprinted genes downstream of the chromatin regulator Trim28. Disruption of Trim28 or of members of this network, including neuronatin, results in an unusual phenotype of a bimodal body weight. To better characterise this variability, we examined the key contributors to energy balance in Nnat^+/-p mice that carry a paternal null allele and do not express Nnat. Consistent with our previous studies, Nnat deficient mice on chow diet displayed a bimodal body weight phenotype with more than 30% of Nnat^+/-p mice developing obesity. In response to both a 45% high fat diet and exposure to thermoneutrality (30 °C) Nnat deficient mice maintained the hypervariable body weight phenotype. Within a calorimetry2021-01-01T00:00:00Z2021 Sep2026-05-08T10:09:45.229Z2022-02-11T10:17:35.525ZS-EPMC84133703447543210.1038/s41598-021-96278-8