Leptin Receptor Co-expression Gene Network Moderates the Effect of Early Life Adversity on Eating Behavior in Children

Overview

Journal Commun Biol

Specialty Biology

Date 2022 Oct 14

PMID 36241774

Authors

Randriely Merscher Sobreira de Lima

Barbara Barth

Danusa Mar Arcego

Euclides Jose de Mendonca Filho

Sachin Patel

Zihan Wang

Irina Pokhvisneva

Carine Parent

Robert D Levitan

Michael S Kobor

Ana Paula Santana de Vasconcellos Bittencourt

Michael J Meaney

Carla Dalmaz

Patricia Pelufo Silveira

Affiliations

Soon will be listed here.

Abstract

Leptin influences eating behavior. Exposure to early adversity is associated with eating behaviour disorders and metabolic syndrome, but the role of the leptin receptor on this relationship is poorly explored. We investigated whether individual differences in brain region specific leptin receptor (LepR) gene networks could moderate the effects of early adversity on eating behavior and metabolism. We created an expression-based polygenic risk score (ePRS) reflecting variations in the function of LepR gene network in prefrontal cortex and hypothalamus to investigate the interactions between a cumulative index of postnatal adversity on eating behavior in two independent birth cohorts (MAVAN and GUSTO). To explore whether variations in the prefrontal cortex or hypothalamic genetic scores could be associated with metabolic measurements, we also assessed the relationship between LepR-ePRS and fasting blood glucose and leptin levels in a third independent cohort (ALSPAC). We identified significant interaction effects between postnatal adversity and prefrontal-based LepR-ePRS on the Child Eating Behavior Questionnaire scores. In MAVAN, we observed a significant interaction effect on food enjoyment at 48 months (β = 61.58, p = 0.015) and 72 months (β = 97.78, p = 0.001); food responsiveness at 48 months (β = 83.79, p = 0.009) satiety at 48 months (β = -43.63, p = 0.047). Similar results were observed in the GUSTO cohort, with a significant interaction effect on food enjoyment (β = 30.48, p = 0.006) food fussiness score (β = -24.07, p = 0.02) and satiety score at 60 months (β = -17.00, p = 0.037). No effects were found when focusing on the hypothalamus-based LepR-ePRS on eating behavior in MAVAN and GUSTO cohorts, and there was no effect of hypothalamus and prefrontal cortex based ePRSs on metabolic measures in ALSPAC. Our study indicated that exposure to postnatal adversity interacts with prefrontal cortex LepR-ePRS to moderate eating behavior, suggesting a neurobiological mechanism associated with the development of eating behavior problems in response to early adversity. The knowledge of these mechanisms may guide the understanding of eating patterns associated with risk for obesity in response to fluctuations in stress exposure early in life.

Citing Articles

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References

Tomiyama A, Schamarek I, Lustig R, Kirschbaum C, Puterman E, Havel P . Leptin concentrations in response to acute stress predict subsequent intake of comfort foods. Physiol Behav. 2012; 107(1):34-9. PMC: 3409346. DOI: 10.1016/j.physbeh.2012.04.021. View

Dalmaz C, Barth B, Pokhvisneva I, Wang Z, Patel S, Quillfeldt J . Prefrontal cortex VAMP1 gene network moderates the effect of the early environment on cognitive flexibility in children. Neurobiol Learn Mem. 2021; 185:107509. DOI: 10.1016/j.nlm.2021.107509. View

Bulik-Sullivan B, Finucane H, Anttila V, Gusev A, Day F, Loh P . An atlas of genetic correlations across human diseases and traits. Nat Genet. 2015; 47(11):1236-41. PMC: 4797329. DOI: 10.1038/ng.3406. View

Dehghani M, Vahidi Mehrjardi M, Dilaver N, Tajamolian M, Enayati S, Ebrahimi P . Potential role of gender specific effect of leptin receptor deficiency in an extended consanguineous family with severe early-onset obesity. Eur J Med Genet. 2018; 61(8):465-467. DOI: 10.1016/j.ejmg.2018.03.006. View

Pauli V, Juge-Aubry C, Boss O, PERNIN A, Chin W, Cusin I . Direct effects of leptin on brown and white adipose tissue. J Clin Invest. 1998; 100(11):2858-64. PMC: 508492. DOI: 10.1172/JCI119834. View

Soares de Oliveira Wertheimer G, Girardi C, de Oliveira A, Longo B, Suchecki D . Maternal deprivation alters growth, food intake, and neuropeptide Y in the hypothalamus of adolescent male and female rats. Dev Psychobiol. 2016; 58(8):1066-1075. DOI: 10.1002/dev.21440. View

Wallace A, McMahon A, Packard C, Kelly A, Shepherd J, Gaw A . Plasma leptin and the risk of cardiovascular disease in the west of Scotland coronary prevention study (WOSCOPS). Circulation. 2001; 104(25):3052-6. DOI: 10.1161/hc5001.101061. View

Wardle J, Guthrie C, Sanderson S, Rapoport L . Development of the Children's Eating Behaviour Questionnaire. J Child Psychol Psychiatry. 2001; 42(7):963-70. DOI: 10.1111/1469-7610.00792. View

Kramer M, Goulet L, Lydon J, Seguin L, McNamara H, Dassa C . Socio-economic disparities in preterm birth: causal pathways and mechanisms. Paediatr Perinat Epidemiol. 2001; 15 Suppl 2:104-23. DOI: 10.1046/j.1365-3016.2001.00012.x. View

10.

Fernandez-Formoso G, Perez-Sieira S, Gonzalez-Touceda D, Dieguez C, Tovar S . Leptin, 20 years of searching for glucose homeostasis. Life Sci. 2015; 140:4-9. DOI: 10.1016/j.lfs.2015.02.008. View

11.

Beck A, Ward C, Mendelson M, Mock J, ERBAUGH J . An inventory for measuring depression. Arch Gen Psychiatry. 1961; 4:561-71. DOI: 10.1001/archpsyc.1961.01710120031004. View

12.

Gillespie C, Phifer J, Bradley B, Ressler K . Risk and resilience: genetic and environmental influences on development of the stress response. Depress Anxiety. 2009; 26(11):984-92. PMC: 2852579. DOI: 10.1002/da.20605. View

13.

Cecil J, Palmer C, Wrieden W, Murrie I, Bolton-Smith C, Watt P . Energy intakes of children after preloads: adjustment, not compensation. Am J Clin Nutr. 2005; 82(2):302-8. DOI: 10.1093/ajcn.82.2.302. View

14.

Gaiteri C, Ding Y, French B, Tseng G, Sibille E . Beyond modules and hubs: the potential of gene coexpression networks for investigating molecular mechanisms of complex brain disorders. Genes Brain Behav. 2013; 13(1):13-24. PMC: 3896950. DOI: 10.1111/gbb.12106. View

15.

Volkow N, Wang G, Fowler J, Telang F . Overlapping neuronal circuits in addiction and obesity: evidence of systems pathology. Philos Trans R Soc Lond B Biol Sci. 2008; 363(1507):3191-200. PMC: 2607335. DOI: 10.1098/rstb.2008.0107. View

16.

Carnell S, Wardle J . Measuring behavioural susceptibility to obesity: validation of the child eating behaviour questionnaire. Appetite. 2006; 48(1):104-13. DOI: 10.1016/j.appet.2006.07.075. View

17.

Silveira P, Pokhvisneva I, Parent C, Cai S, Sathyapalan Rema A, Broekman B . Cumulative prenatal exposure to adversity reveals associations with a broad range of neurodevelopmental outcomes that are moderated by a novel, biologically informed polygenetic score based on the serotonin transporter solute carrier family C6,.... Dev Psychopathol. 2017; 29(5):1601-1617. DOI: 10.1017/S0954579417001262. View

18.

Newberger E, Barkan S, Lieberman E, McCormick M, Yllo K, Gary L . Abuse of pregnant women and adverse birth outcome. Current knowledge and implications for practice. JAMA. 1992; 267(17):2370-2. View

19.

McCarthy S, Das S, Kretzschmar W, Delaneau O, Wood A, Teumer A . A reference panel of 64,976 haplotypes for genotype imputation. Nat Genet. 2016; 48(10):1279-83. PMC: 5388176. DOI: 10.1038/ng.3643. View

20.

Ahima R, Antwi D . Brain regulation of appetite and satiety. Endocrinol Metab Clin North Am. 2008; 37(4):811-23. PMC: 2710609. DOI: 10.1016/j.ecl.2008.08.005. View