Maternal dietary fat during lactation shapes single nucleus transcriptomic profile of postnatal offspring hypothalamus in a sexually dimorphic manner in mice.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
16 Mar 2024
16 Mar 2024
Historique:
received:
28
09
2023
accepted:
01
03
2024
medline:
18
3
2024
pubmed:
17
3
2024
entrez:
17
3
2024
Statut:
epublish
Résumé
Maternal overnutrition during lactation predisposes offspring to develop metabolic diseases and exacerbates the relevant syndromes in males more than females in later life. The hypothalamus is a heterogenous brain region that regulates energy balance. Here we combined metabolic trait quantification of mother and offspring mice under low and high fat diet (HFD) feeding during lactation, with single nucleus transcriptomic profiling of their offspring hypothalamus at peak lacation to understand the cellular and molecular alterations in response to maternal dietary pertubation. We found significant expansion in neuronal subpopulations including histaminergic (Hdc), arginine vasopressin/retinoic acid receptor-related orphan receptor β (Avp/Rorb) and agouti-related peptide/neuropeptide Y (AgRP/Npy) in male offspring when their mothers were fed HFD, and increased Npy-astrocyte interactions in offspring responding to maternal overnutrition. Our study provides a comprehensive offspring hypothalamus map at the peak lactation and reveals how the cellular subpopulations respond to maternal dietary fat in a sex-specific manner during development.
Identifiants
pubmed: 38493217
doi: 10.1038/s41467-024-46589-x
pii: 10.1038/s41467-024-46589-x
doi:
Substances chimiques
Dietary Fats
0
Neuropeptide Y
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
2382Subventions
Organisme : National Natural Science Foundation of China (National Science Foundation of China)
ID : 32371195
Informations de copyright
© 2024. The Author(s).
Références
World Health Organization. Obesity and overweight. https://www.who.int/news-room/fact-sheets/detail/obesity-and-overweight (2024).
Du, Q. et al. Postnatal weight gain induced by overfeeding pups and maternal high-fat diet during the lactation period modulates glucose metabolism and the production of pancreatic and gastrointestinal peptides. Peptides 70, 23–31 (2015).
pubmed: 26022984
doi: 10.1016/j.peptides.2015.05.003
Gorski, J. N. et al. Postnatal environment overrides genetic and prenatal factors influencing offspring obesity and insulin resistance. Am. J. Physiol. Regul. Integr. Comp. Physiol. 291, R768–R778 (2006).
pubmed: 16614055
doi: 10.1152/ajpregu.00138.2006
Guillaumin, M. C. C. et al. Maternal over- and malnutrition and increased risk for addictive and eating disorders in the offspring. Nutrients 15, 1095 (2023).
pubmed: 36904093
pmcid: 10004806
doi: 10.3390/nu15051095
Li, C. et al. Amylin receptor insensitivity impairs hypothalamic POMC neuron differentiation in the male offspring of maternal high-fat diet-fed mice. Mol. Metab. 44, 101135 (2021).
pubmed: 33279727
doi: 10.1016/j.molmet.2020.101135
Sun, B. et al. Maternal high-fat diet during gestation or suckling differentially affects offspring leptin sensitivity and obesity. Diabetes 61, 2833–2841 (2012).
pubmed: 22751689
pmcid: 3478561
doi: 10.2337/db11-0957
Vithayathil, M. A. et al. Exposure to maternal cafeteria diets during the suckling period has greater effects on fat deposition and Sterol Regulatory Element Binding Protein-1c (SREBP-1c) gene expression in rodent offspring compared to exposure before birth. Nutr. Metab. 15, 17 (2018).
doi: 10.1186/s12986-018-0253-3
Vogt, M. C. et al. Neonatal insulin action impairs hypothalamic neurocircuit formation in response to maternal high-fat feeding. Cell 156, 495–509 (2014).
pubmed: 24462248
pmcid: 4101521
doi: 10.1016/j.cell.2014.01.008
Andreas, N. J. et al. Human breast milk: a review on its composition and bioactivity. Early Hum. Dev. 91, 629–635 (2015).
pubmed: 26375355
doi: 10.1016/j.earlhumdev.2015.08.013
Eisha, S. et al. Non-nutritive bioactive components in maternal milk and offspring development: a scoping review. J. Dev. Orig. Health Dis. 13, 665–673 (2022).
pubmed: 35387707
doi: 10.1017/S2040174422000149
Chang, G. Q. et al. Maternal high-fat diet and fetal programming: increased proliferation of hypothalamic peptide-producing neurons that increase risk for overeating and obesity. J. Neurosci. 28, 12107–12119 (2008).
pubmed: 19005075
pmcid: 2752048
doi: 10.1523/JNEUROSCI.2642-08.2008
de Paula Simino, L. A. et al. Lipid overload during gestation and lactation can independently alter lipid homeostasis in offspring and promote metabolic impairment after new challenge to high-fat diet. Nutr. Metab. 14, 16 (2017).
doi: 10.1186/s12986-017-0168-4
Gregorio, B. M. et al. Maternal high-fat intake predisposes nonalcoholic fatty liver disease in C57BL/6 offspring. Am. J. Obstet. Gynecol. 203, 495 e491–495.e498 (2010).
doi: 10.1016/j.ajog.2010.06.042
Kruse, M. et al. High-fat intake during pregnancy and lactation exacerbates high-fat diet-induced complications in male offspring in mice. Endocrinology 154, 3565–3576 (2013).
pubmed: 23861375
pmcid: 3776861
doi: 10.1210/en.2012-1877
Samuelsson, A. M. et al. Diet-induced obesity in female mice leads to offspring hyperphagia, adiposity, hypertension, and insulin resistance: a novel murine model of developmental programming. Hypertension 51, 383–392 (2008).
pubmed: 18086952
doi: 10.1161/HYPERTENSIONAHA.107.101477
Tain, Y. L. et al. Maternal high fructose intake increases the vulnerability to post-weaning high-fat diet-induced programmed hypertension in male offspring. Nutrients 10, 56 (2018).
pubmed: 29315230
pmcid: 5793284
doi: 10.3390/nu10010056
Singhal, A. et al. Nutrition in infancy and long-term risk of obesity: evidence from 2 randomized controlled trials. Am. J. Clin. Nutr. 92, 1133–1144 (2010).
pubmed: 20881062
doi: 10.3945/ajcn.2010.29302
Huang, Y. et al. Impact of graded maternal dietary fat content on offspring susceptibility to high-fat diet in mice. Obesity 29, 2055–2067 (2021).
pubmed: 34813173
doi: 10.1002/oby.23270
Dearden, L. et al. Sexual dimorphism in offspring glucose-sensitive hypothalamic gene expression and physiological responses to maternal high-fat diet feeding. Endocrinology 155, 2144–2154 (2014).
pubmed: 24684305
pmcid: 4183922
doi: 10.1210/en.2014-1131
Masuyama, H. et al. Additive effects of maternal high fat diet during lactation on mouse offspring. PLoS One 9, e92805 (2014).
pubmed: 24664181
pmcid: 3963955
doi: 10.1371/journal.pone.0092805
Nicholas, L. M. et al. Exposure to maternal obesity programs sex differences in pancreatic islets of the offspring in mice. Diabetologia 63, 324–337 (2020).
pubmed: 31773193
doi: 10.1007/s00125-019-05037-y
Huang, Y. et al. Limits to sustained energy intake. XXXI. Effect of graded levels of dietary fat on lactation performance in Swiss mice. J. Exp. Biol. 223, jeb221911 (2020).
pubmed: 32291324
doi: 10.1242/jeb.221911
Barbero, A. et al. Maternal malnutrition and offspring sex determine juvenile obesity and metabolic disorders in a swine model of leptin resistance. PLoS One 8, e78424 (2013).
pubmed: 24205230
pmcid: 3813450
doi: 10.1371/journal.pone.0078424
Melo, G. M. et al. Overnutrition during pregnancy and lactation induces gender-dependent dysmetabolism in the offspring accompanied by heightened stress and anxiety. Nutrients 16, 67 (2023).
pubmed: 38201896
pmcid: 10781034
doi: 10.3390/nu16010067
Monks, J. et al. Maternal obesity during lactation may protect offspring from high fat diet-induced metabolic dysfunction. Nutr. Diabetes 8, 18 (2018).
pubmed: 29695710
pmcid: 5916951
doi: 10.1038/s41387-018-0027-z
Lee, D. A. et al. Functional implications of hypothalamic neurogenesis in the adult mammalian brain. Int J. Dev. Neurosci. 30, 615–621 (2012).
pubmed: 22867732
pmcid: 3906127
doi: 10.1016/j.ijdevneu.2012.07.003
Lee, D. A. et al. Dietary and sex-specific factors regulate hypothalamic neurogenesis in young adult mice. Front. Neurosci. 8, 157 (2014).
pubmed: 24982613
pmcid: 4056383
doi: 10.3389/fnins.2014.00157
Orikasa, C. Social network plasticity of mice parental behavior. Front. Neurosci. 16, 882850 (2022).
pubmed: 35747212
pmcid: 9209706
doi: 10.3389/fnins.2022.882850
Yoo, S. et al. Regulation and function of neurogenesis in the adult mammalian hypothalamus. Prog. Neurobiol. 170, 53–66 (2018).
pubmed: 29631023
pmcid: 6173995
doi: 10.1016/j.pneurobio.2018.04.001
Deng, X. H. et al. Glial transcripts and immune-challenged glia in the suprachiasmatic nucleus of young and aged mice. Chronobiol. Int. 27, 742–767 (2010).
pubmed: 20560709
doi: 10.3109/07420521003681498
Kalin, S. et al. Hypothalamic innate immune reaction in obesity. Nat. Rev. Endocrinol. 11, 339–351 (2015).
pubmed: 25824676
doi: 10.1038/nrendo.2015.48
Lee, C. H. et al. Cellular contributors to hypothalamic inflammation in obesity. Mol. Cells 43, 431–437 (2020).
pubmed: 32392909
pmcid: 7264480
Timper, K. et al. Hypothalamic circuits regulating appetite and energy homeostasis: pathways to obesity. Dis. Model Mech. 10, 679–689 (2017).
pubmed: 28592656
pmcid: 5483000
doi: 10.1242/dmm.026609
Wang, Y. Q. et al. Fasting activated histaminergic neurons and enhanced arousal effect of caffeine in mice. Pharm. Biochem. Behav. 133, 164–173 (2015).
doi: 10.1016/j.pbb.2015.04.003
Ahima, R. S. et al. Brain regulation of appetite and satiety. Endocrinol. Metab. Clin. North Am. 37, 811–823 (2008).
pubmed: 19026933
pmcid: 2710609
doi: 10.1016/j.ecl.2008.08.005
Luquet, S. et al. NPY/AgRP neurons are essential for feeding in adult mice but can be ablated in neonates. Science 310, 683–685 (2005).
pubmed: 16254186
doi: 10.1126/science.1115524
Myers, M. G. Jr. et al. Central nervous system control of metabolism. Nature 491, 357–363 (2012).
pubmed: 23151578
doi: 10.1038/nature11705
Schwartz, M. W. et al. Central nervous system control of food intake. Nature 404, 661–671 (2000).
pubmed: 10766253
doi: 10.1038/35007534
Sohn, J. W. Network of hypothalamic neurons that control appetite. BMB Rep. 48, 229–233 (2015).
pubmed: 25560696
pmcid: 4436859
doi: 10.5483/BMBRep.2015.48.4.272
Gout, J. et al. Metabolic and melanocortin gene expression alterations in male offspring of obese mice. Mol. Cell Endocrinol. 319, 99–108 (2010).
pubmed: 20097259
doi: 10.1016/j.mce.2010.01.021
Schellong, K. et al. Sex-specific epigenetic alterations of the hypothalamic Agrp-Pomc system do not explain ‘diabesity’ in the offspring of high-fat diet (HFD) overfed maternal rats. J. Nutr. Biochem. 75, 108257 (2020).
pubmed: 31710935
doi: 10.1016/j.jnutbio.2019.108257
Xu, Y. et al. Maternal high fat diet in lactation impacts hypothalamic neurogenesis and neurotrophic development, leading to later life susceptibility to obesity in male but not female mice. Adv. Sci. 10, 2305472 (2023).
Gawlinska, K. et al. A maternal high-fat diet during early development provokes molecular changes related to autism spectrum disorder in the rat offspring brain. Nutrients 13, 3212 (2021).
pubmed: 34579089
pmcid: 8467420
doi: 10.3390/nu13093212
Gawlinska, K. et al. Maternal dietary patterns are associated with susceptibility to a depressive-like phenotype in rat offspring. Dev. Cogn. Neurosci. 47, 100879 (2021).
pubmed: 33232913
doi: 10.1016/j.dcn.2020.100879
Wankhade, U. D. et al. Enhanced offspring predisposition to steatohepatitis with maternal high-fat diet is associated with epigenetic and microbiome alterations. PLoS One 12, e0175675 (2017).
pubmed: 28414763
pmcid: 5393586
doi: 10.1371/journal.pone.0175675
Huisman, C. et al. Single cell transcriptome analysis of developing arcuate nucleus neurons uncovers their key developmental regulators. Nat. Commun. 10, 3696 (2019).
pubmed: 31420539
pmcid: 6697706
doi: 10.1038/s41467-019-11667-y
Xu, S. et al. Behavioral state coding by molecularly defined paraventricular hypothalamic cell type ensembles. Science 370, eabb2494 (2020).
pubmed: 33060330
doi: 10.1126/science.abb2494
Yu, H. et al. Developmental single-cell transcriptomics of hypothalamic POMC neurons reveal the genetic trajectories of multiple neuropeptidergic phenotypes. Elife 11, e72883 (2022).
pubmed: 35044906
pmcid: 8806186
doi: 10.7554/eLife.72883
Zhang, Y. H. et al. Cascade diversification directs generation of neuronal diversity in the hypothalamus. Cell Stem Cell 28, 1483–1499 e1488 (2021).
pubmed: 33887179
doi: 10.1016/j.stem.2021.03.020
Hajdarovic, K. H. et al. Single-cell analysis of the aging female mouse hypothalamus. Nat. Aging 2, 662–678 (2022).
pubmed: 36285248
pmcid: 9592060
doi: 10.1038/s43587-022-00246-4
Campbell, J. N. et al. A molecular census of arcuate hypothalamus and median eminence cell types. Nat. Neurosci. 20, 484–496 (2017).
pubmed: 28166221
pmcid: 5323293
doi: 10.1038/nn.4495
Chen, R. et al. Single-Cell RNA-Seq reveals hypothalamic cell diversity. Cell Rep. 18, 3227–3241 (2017).
pubmed: 28355573
pmcid: 5782816
doi: 10.1016/j.celrep.2017.03.004
Kim, D. W. et al. The cellular and molecular landscape of hypothalamic patterning and differentiation from embryonic to late postnatal development. Nat. Commun. 11, 4360 (2020).
pubmed: 32868762
pmcid: 7459115
doi: 10.1038/s41467-020-18231-z
Mickelsen, L. E. et al. Single-cell transcriptomic analysis of the lateral hypothalamic area reveals molecularly distinct populations of inhibitory and excitatory neurons. Nat. Neurosci. 22, 642–656 (2019).
pubmed: 30858605
pmcid: 7043322
doi: 10.1038/s41593-019-0349-8
Mickelsen, L. E. et al. Cellular taxonomy and spatial organization of the murine ventral posterior hypothalamus. Elife 9, e58901 (2020).
pubmed: 33119507
pmcid: 7595735
doi: 10.7554/eLife.58901
Romanov, R. A. et al. Molecular interrogation of hypothalamic organization reveals distinct dopamine neuronal subtypes. Nat. Neurosci. 20, 176–188 (2017).
pubmed: 27991900
doi: 10.1038/nn.4462
Wen, S. et al. Spatiotemporal single-cell analysis of gene expression in the mouse suprachiasmatic nucleus. Nat. Neurosci. 23, 456–467 (2020).
pubmed: 32066983
doi: 10.1038/s41593-020-0586-x
Romanov, R. A. et al. Molecular design of hypothalamus development. Nature 582, 246–252 (2020).
pubmed: 32499648
pmcid: 7292733
doi: 10.1038/s41586-020-2266-0
Steuernagel, L. et al. HypoMap-a unified single-cell gene expression atlas of the murine hypothalamus. Nat. Metab. 4, 1402–1419 (2022).
pubmed: 36266547
pmcid: 9584816
doi: 10.1038/s42255-022-00657-y
Johnson, M. S. et al. Limits to sustained energy intake. V. Effect of cold-exposure during lactation in Mus musculus. J. Exp. Biol. 204, 1967–1977 (2001).
pubmed: 11441038
doi: 10.1242/jeb.204.11.1967
Velmeshev, D. et al. Single-cell genomics identifies cell type-specific molecular changes in autism. Science 364, 685–689 (2019).
pubmed: 31097668
pmcid: 7678724
doi: 10.1126/science.aav8130
Zhao, J. et al. Detection of differentially abundant cell subpopulations in scRNA-seq data. Proc. Natl. Acad. Sci. USA 118, e2100293118 (2021).
pubmed: 34001664
pmcid: 8179149
doi: 10.1073/pnas.2100293118
Liu, Y. et al. Interactions of glial cells with neuronal synapses, from astrocytes to microglia and oligodendrocyte lineage cells. Glia 71, 1383–1401 (2023).
pubmed: 36799296
doi: 10.1002/glia.24343
Lattke, M. et al. Extensive transcriptional and chromatin changes underlie astrocyte maturation in vivo and in culture. Nat. Commun. 12, 4335 (2021).
pubmed: 34267208
pmcid: 8282848
doi: 10.1038/s41467-021-24624-5
Huang, H. T. et al. Chronic exposure to high fat diet triggers myelin disruption and interleukin-33 upregulation in hypothalamus. BMC Neurosci. 20, 33 (2019).
pubmed: 31291887
pmcid: 6617565
doi: 10.1186/s12868-019-0516-6
Moraes, J. C. et al. High-fat diet induces apoptosis of hypothalamic neurons. PLoS One 4, e5045 (2009).
pubmed: 19340313
pmcid: 2661137
doi: 10.1371/journal.pone.0005045
Kang, J. B. et al. Efficient and precise single-cell reference atlas mapping with Symphony. Nat. Commun. 12, 5890 (2021).
pubmed: 34620862
pmcid: 8497570
doi: 10.1038/s41467-021-25957-x
Buttner, M. et al. scCODA is a Bayesian model for compositional single-cell data analysis. Nat. Commun. 12, 6876 (2021).
pubmed: 34824236
pmcid: 8616929
doi: 10.1038/s41467-021-27150-6
Yoshimura, M. et al. Arginine vasopressin: direct and indirect action on metabolism. Peptides 142, 170555 (2021).
pubmed: 33905792
pmcid: 8270887
doi: 10.1016/j.peptides.2021.170555
Mohan, S. et al. Weight-reducing, lipid-lowering and antidiabetic activities of a novel arginine vasopressin analogue acting at the V1a and V1b receptors in high-fat-fed mice. Diabetes Obes. Metab. 23, 2215–2225 (2021).
pubmed: 34105240
doi: 10.1111/dom.14462
Fosch, A. et al. New Insights of SF1 neurons in hypothalamic regulation of obesity and diabetes. Int. J. Mol. Sci. 22, 6186 (2021).
pubmed: 34201257
pmcid: 8229730
doi: 10.3390/ijms22126186
Donato, J. Jr. et al. Hypothalamic sites of leptin action linking metabolism and reproduction. Neuroendocrinology 93, 9–18 (2011).
pubmed: 21099209
doi: 10.1159/000322472
Xu, J. et al. Genetic identification of leptin neural circuits in energy and glucose homeostases. Nature 556, 505–509 (2018).
pubmed: 29670283
pmcid: 5920723
doi: 10.1038/s41586-018-0049-7
Deng, G. et al. Single-Nucleus RNA sequencing of the hypothalamic arcuate nucleus of C57BL/6J mice after prolonged diet-induced obesity. Hypertension 76, 589–597 (2020).
pubmed: 32507042
doi: 10.1161/HYPERTENSIONAHA.120.15137
Kohnke, S. et al. Nutritional regulation of oligodendrocyte differentiation regulates perineuronal net remodeling in the median eminence. Cell Rep. 36, 109362 (2021).
pubmed: 34260928
pmcid: 8293628
doi: 10.1016/j.celrep.2021.109362
Troadec, J. D. et al. Glial modulation of energy balance: the dorsal vagal complex is no exception. Int. J. Mol. Sci. 23, 960 (2022).
pubmed: 35055143
pmcid: 8779587
doi: 10.3390/ijms23020960
Butruille, L. et al. Maternal high-fat diet during suckling programs visceral adiposity and epigenetic regulation of adipose tissue stearoyl-CoA desaturase-1 in offspring. Int. J. Obes. 43, 2381–2393 (2019).
doi: 10.1038/s41366-018-0310-z
Howie, G. J. et al. Maternal nutritional history predicts obesity in adult offspring independent of postnatal diet. J. Physiol. 587, 905–915 (2009).
pubmed: 19103681
doi: 10.1113/jphysiol.2008.163477
Kagya-Agyemang, J. K. et al. Limits to sustained energy intake. XXVIII. Beneficial effects of high dietary fat on lactation performance in mice. J. Exp. Biol. 221, jeb180828 (2018).
pubmed: 29941615
doi: 10.1242/jeb.180828
Vucetic, Z. et al. Maternal high-fat diet alters methylation and gene expression of dopamine and opioid-related genes. Endocrinology 151, 4756–4764 (2010).
pubmed: 20685869
pmcid: 2946145
doi: 10.1210/en.2010-0505
Dearden, L. et al. Maternal obesity causes fetal hypothalamic insulin resistance and disrupts development of hypothalamic feeding pathways. Mol. Metab. 42, 101079 (2020).
pubmed: 32919096
pmcid: 7549144
doi: 10.1016/j.molmet.2020.101079
Lemes, S. F. et al. Maternal consumption of high-fat diet in mice alters hypothalamic notch pathway, NPY cell population and food intake in offspring. Neuroscience 371, 1–15 (2018).
pubmed: 29203230
doi: 10.1016/j.neuroscience.2017.11.043
Haas, H. L. et al. Histamine in the nervous system. Physiol. Rev. 88, 1183–1241 (2008).
pubmed: 18626069
doi: 10.1152/physrev.00043.2007
Yoshimatsu, H. et al. Histidine suppresses food intake through its conversion into neuronal histamine. Exp. Biol. Med. 227, 63–68 (2002).
doi: 10.1177/153537020222700111
Yoshimatsu, H. et al. Hypothalamic neuronal histamine as a target of leptin in feeding behavior. Diabetes 48, 2286–2291 (1999).
pubmed: 10580415
doi: 10.2337/diabetes.48.12.2286
Miklos, I. H. et al. Functional heterogeneity of the responses of histaminergic neuron subpopulations to various stress challenges. Eur. J. Neurosci. 18, 3069–3079 (2003).
pubmed: 14656302
doi: 10.1111/j.1460-9568.2003.03033.x
Pei, H. et al. AVP neurons in the paraventricular nucleus of the hypothalamus regulate feeding. Mol. Metab. 3, 209–215 (2014).
pubmed: 24634830
pmcid: 3953699
doi: 10.1016/j.molmet.2013.12.006
Challet, E. The circadian regulation of food intake. Nat. Rev. Endocrinol. 15, 393–405 (2019).
pubmed: 31073218
doi: 10.1038/s41574-019-0210-x
Bedont, J. L. et al. Lhx1 controls terminal differentiation and circadian function of the suprachiasmatic nucleus. Cell Rep. 7, 609–622 (2014).
pubmed: 24767996
pmcid: 4254772
doi: 10.1016/j.celrep.2014.03.060
Ko, C. H. et al. Emergence of noise-induced oscillations in the central circadian pacemaker. PLoS Biol. 8, e1000513 (2010).
pubmed: 20967239
pmcid: 2953532
doi: 10.1371/journal.pbio.1000513
Horvath, T. L. et al. Synaptic input organization of the melanocortin system predicts diet-induced hypothalamic reactive gliosis and obesity. Proc. Natl. Acad. Sci. USA 107, 14875–14880 (2010).
pubmed: 20679202
pmcid: 2930476
doi: 10.1073/pnas.1004282107
Lutomska, L. M. et al. Diet triggers specific responses of hypothalamic astrocytes in time and region dependent manner. Glia 70, 2062–2078 (2022).
pubmed: 35802021
doi: 10.1002/glia.24237
Locke, A. E. et al. Genetic studies of body mass index yield new insights for obesity biology. Nature 518, 197–206 (2015).
pubmed: 25673413
pmcid: 4382211
doi: 10.1038/nature14177
Turcot, V. et al. Protein-altering variants associated with body mass index implicate pathways that control energy intake and expenditure in obesity. Nat. Genet. 50, 26–41 (2018).
pubmed: 29273807
doi: 10.1038/s41588-017-0011-x
Yengo, L. et al. Meta-analysis of genome-wide association studies for height and body mass index in approximately 700000 individuals of European ancestry. Hum. Mol. Genet. 27, 3641–3649 (2018).
pubmed: 30124842
pmcid: 6488973
doi: 10.1093/hmg/ddy271
Poelmans, G. et al. Integrated genome-wide association study findings: identification of a neurodevelopmental network for attention deficit hyperactivity disorder. Am. J. Psychiatry 168, 365–377 (2011).
pubmed: 21324949
doi: 10.1176/appi.ajp.2010.10070948
Schork, A. J. et al. A genome-wide association study of shared risk across psychiatric disorders implicates gene regulation during fetal neurodevelopment. Nat. Neurosci. 22, 353–361 (2019).
pubmed: 30692689
pmcid: 6497521
doi: 10.1038/s41593-018-0320-0
Yang, L. et al. Polygenic transmission and complex neuro developmental network for attention deficit hyperactivity disorder: genome-wide association study of both common and rare variants. Am. J. Med. Genet. B Neuropsychiatr. Genet. 162B, 419–430 (2013).
pubmed: 23728934
doi: 10.1002/ajmg.b.32169
Cirera, S. et al. Expression studies of six human obesity-related genes in seven tissues from divergent pig breeds. Anim. Genet. 45, 59–66 (2014).
pubmed: 24033492
doi: 10.1111/age.12082
Loos, R. J. F. et al. The genetics of obesity: from discovery to biology. Nat. Rev. Genet. 23, 120−133 (2022).
Speakman, J. R. Functional analysis of seven genes linked to body mass index and adiposity by genome-wide association studies: a review. Hum. Hered. 75, 57–79 (2013).
pubmed: 24081222
doi: 10.1159/000353585
Schafer, M. et al. Neurotractin/kilon promotes neurite outgrowth and is expressed on reactive astrocytes after entorhinal cortex lesion. Mol. Cell Neurosci. 29, 580–590 (2005).
pubmed: 15946856
doi: 10.1016/j.mcn.2005.04.010
Singh, K. et al. Neural cell adhesion molecule Negr1 deficiency in mouse results in structural brain endophenotypes and behavioral deviations related to psychiatric disorders. Sci. Rep. 9, 5457 (2019).
pubmed: 30932003
pmcid: 6443666
doi: 10.1038/s41598-019-41991-8
Matikainen-Ankney, B. A. et al. Persistent effects of obesity: a neuroplasticity hypothesis. Ann. N. Y Acad. Sci. 1428, 221–239 (2018).
pubmed: 29741270
pmcid: 6158064
doi: 10.1111/nyas.13665
Butler, P. J. et al. Measuring metabolic rate in the field: the pros and cons of the doubly labelled water and heart rate methods. Functional Ecol. 18, 168–183 (2004).
Krol, E. et al. Limits to sustained energy intake. VII. Milk energy output in laboratory mice at thermoneutrality. J. Exp. Biol. 206, 4267–4281 (2003).
pubmed: 14581597
doi: 10.1242/jeb.00675
Krol, E. et al. Isotope dilution spaces of mice injected simultaneously with deuterium, tritium and oxygen-18. J. Exp. Biol. 202, 2839–2849 (1999).
pubmed: 10504320
doi: 10.1242/jeb.202.20.2839
Nagy, K. A. The doubly labeled water (
Speakman, J. R. et al. Comparison of different approaches for the calculation of energy expenditure using doubly labeled water in a small mammal. Physiol. Biochem. Zool. 78, 650–667 (2005).
pubmed: 15957119
doi: 10.1086/430234
Speakman, J. Doubly labelled water: theory and practice. (Springer Science & Business Media, 1997).
Speakman, J. How Should We Calculate CO
Weir, J. B. New methods for calculating metabolic rate with special reference to protein metabolism. J. Physiol. 109, 1–9 (1949).
pubmed: 15394301
pmcid: 1392602
doi: 10.1113/jphysiol.1949.sp004363
Yu, G. et al. clusterProfiler: an R package for comparing biological themes among gene clusters. OMICS 16, 284–287 (2012).
pubmed: 22455463
pmcid: 3339379
doi: 10.1089/omi.2011.0118
Ashburner, M. et al. Gene ontology: tool for the unification of biology. The Gene Ontology Consortium. Nat. Genet. 25, 25–29 (2000).
pubmed: 10802651
pmcid: 3037419
doi: 10.1038/75556
Tschop, M. H. et al. A guide to analysis of mouse energy metabolism. Nat. Methods 9, 57–63 (2011).
pubmed: 22205519
pmcid: 3654855
doi: 10.1038/nmeth.1806
Huang, Y. et al. Maternal dietary fat during lactation shapes single nucleus transcriptomic landscape of postnatal offspring hypothalamus in a sexually dimorphic manner in mice (MouseHypothalamus_snRNA-Analysis-v1.0.1). Zenodo, https://doi.org/10.5281/zenodo.10654924 (2024).