The influence of parental high-fat high-sugar diet on the gut-brain axis in male offspring
Abstract
Purpose The gut-brain axis (GBA) is implicated in the development of obesity, and its role in developmental programming needs to be explored. This study uncovers the effects of a parental high-fat, high-sugar diet (HFS) on the gut (colon) and brain (hypothalamus) GBA of male Wistar rat offspring at weaning until adulthood.Methods For ten weeks before mating, male progenitors were fed a control diet (CD) or HFS, whereas dams were fed CD or HFS during pregnancy and lactation. Male offspring aged 21-and 90-day old were assessed for: Gene expression of toll-like receptor 4 (TLR4) pathway and zonula occludens 1 (ZO1) in the colon and hypothalamus; hypothalamic gene expression of orexigenic neuropeptides and Leptin receptor; serum levels of lipopolysaccharide (LPS), glucagon like peptide 1 (GLP-1), Ghrelin and neuropeptide Y (NPY); colonic cytokine levels; FaecalBifidobacterium spp.andLactobacillus spp. DNA.Results Paternal HFS showed increased endotoxaemia, reduced colonic gene expression of ZO1 and reduced colonic TNF-α at weaning. In the adult offspring, paternal HFS showed increased NPY, reduced serum Ghrelin, colonic pro-inflammatory cytokines, and lower faecalBifidobacteriumspp. DNA. Maternal diet showed increased hypothalamic gene expression of myeloid differentiation primary response 88 (MYD88) at weaning. The maternal HFS diet showed increased NPY and reduced faecalBifidobacteriumspp. andLactobacillusspp. DNA in the adult offspring. The combined effect of parental diet showed increased NPY at weaning, and lowerBifidobacteriumspp. andLactobacillus spp.in the adult offspring.Conclusion Maternal and paternal HFS diet seem to influence the programming of the gut-brain axis, leading to increased visceral adiposity and weight of male offspring at weaning, the effect that lasted until adulthood.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Lipopolysaccharide (LPS) plays a key role in the communication between the gut and the brain, as it has a remarkable proinflammatory effect.
“Lipopolysaccharide (LPS) appears to play a key role in the communication between the gut and the brain, as it has a remarkable proinflammatory effect [70]”
From Healthy Human Fecal Microbiota Transplantation into Mice Attenuates MPTP-Induced Neurotoxicity <i>via</i> AMPK/SOD2 Pathway (2023) · cites this paper as [70]
Cites
Analysis of Relative Gene Expression Data Using Real-Time Quantitative PCR and the 2−ΔΔCT Method
Livak, K. J., & Schmittgen, T. D. (2001) · Methods · doi:10.1006/meth.2001.1262 · Cited by 180,860 · see citing works
Interactions between the microbiota, immune and nervous systems in health and disease
Fung, T. C., Olson, C. A., & Hsiao, E. Y. (2017) · Nature Neuroscience · doi:10.1038/nn.4476 · Cited by 1,900 · see citing works
Sperm tsRNAs contribute to intergenerational inheritance of an acquired metabolic disorder
Chen, Q., Yan, M., Cao, Z., Li, X., Zhang, Y., Shi, J., Feng, G.-H., Peng, H., Zhang, X., Zhang, Y., et al. (2016) · Science · doi:10.1126/science.aad7977 · Cited by 1,470 · see citing works
Hypothalamic IKKβ/NF-κB and ER Stress Link Overnutrition to Energy Imbalance and Obesity
Zhang, X., Zhang, G., Zhang, H., Karin, M., Bai, H., & Cai, D. (2008) · Cell · doi:10.1016/j.cell.2008.07.043 · Cited by 1,350 · see citing works
Kim, K., Gu, W., Lee, I., Joh, E., & Kim, D. (2012) · PLoS ONE · doi:10.1371/journal.pone.0047713 · Cited by 1,184 · see citing works
Rodgers, A. B., Morgan, C. P., Bronson, S. L., Revello, S., & Bale, T. L. (2013) · The Journal of Neuroscience · doi:10.1523/jneurosci.0914-13.2013 · Cited by 814 · see citing works
Hypothalamic circuits regulating appetite and energy homeostasis: pathways to obesity
Timper, K., & Brüning, J. C. (2017) · Disease Models & Mechanisms · doi:10.1242/dmm.026609 · Cited by 802 · see citing works
The microbiota-gut-brain axis in obesity.
Torres-Fuentes, C., Schellekens, H., Dinan, T., & Cryan, J. (2017) · The Lancet Gastroenterology and Hepatology · doi:10.1016/s2468-1253(17)30147-4 · Cited by 506 · see citing works
Neuropeptide, Y, peptide YY and pancreatic polypeptide in the gut-brain axis
Holzer, P., Reichmann, F., & Farzi, A. (2012) · Neuropeptides · doi:10.1016/j.npep.2012.08.005 · Cited by 501 · see citing works
Valdearcos, M., Douglass, J. D., Robblee, M. M., Dorfman, M. D., Stifler, D. R., Bennett, M. L., Gerritse, I., Fasnacht, R., Barres, B. A., Thaler, J. P., et al. (2017) · Cell Metabolism · doi:10.1016/j.cmet.2017.05.015 · Cited by 477 · see citing works
Neuropeptides and the Microbiota-Gut-Brain Axis
Holzer, P., & Farzi, A. (2014) · Advances in Experimental Medicine and Biology · doi:10.1007/978-1-4939-0897-4_9 · Cited by 451 · see citing works
Ma, J., Prince, A., Bader, D., Hu, M., Ganu, R., Baquero, K. C., Blundell, P., Harris, R. A., Frias, A. E., Grove, K. L., et al. (2014) · Nature Communications · doi:10.1038/ncomms4889 · Cited by 440 · see citing works
New-found link between microbiota and obesity
Chakraborti, C. K. (2015) · World Journal of Gastrointestinal Pathophysiology · doi:10.4291/wjgp.v6.i4.110 · Cited by 378 · see citing works
Hyperleptinemia Is Required for the Development of Leptin Resistance
Knight, Z. A., Hannan, K. S., Greenberg, M. L., & Friedman, J. M. (2010) · PLoS ONE · doi:10.1371/journal.pone.0011376 · Cited by 311 · see citing works
Sperm Microbiota and Its Impact on Semen Parameters
Baud, D., Pattaroni, C., Vulliémoz, N. R., Castella, V., Marsland, B. J., & Stojanov, M. (2019) · Frontiers in Microbiology · doi:10.3389/fmicb.2019.00234 · Cited by 234 · see citing works
POHaD: why we should study future fathers
Soubry, A. (2018) · Current Zoology · doi:10.1093/eep/dvy007 · Cited by 218 · see citing works
Satiety Mechanisms in Genetic Risk of Obesity
Llewellyn, C. H., Trzaskowski, M., van Jaarsveld, C. H. M., Plomin, R. J., & Wardle, J. (2014) · Archives of Pediatrics and Adolescent Medicine · doi:10.1001/jamapediatrics.2013.4944 · Cited by 201 · see citing works
Parental Dietary Fat Intake Alters Offspring Microbiome and Immunity
Myles, I. A., Fontecilla, N. M., Janelsins, B., Vithayathil, P. J., Segre, J. A., & Datta, S. K. (2013) · The Journal of Immunology · doi:10.4049/jimmunol.1301057 · Cited by 174 · see citing works
D'Mello, C., Ronaghan, N., Zaheer, R., Dicay, M., Le, T., MacNaughton, W. K., Surrette, M. G., & Swain, M. G. (2015) · Journal of Neuroscience · doi:10.1523/jneurosci.0575-15.2015 · Cited by 169 · see citing works
Hassan, A. M., Mancano, G., Kashofer, K., Fröhlich, E. E., Matak, A., Mayerhofer, R., Reichmann, F., Olivares, M., Neyrinck, A. M., Delzenne, N. M., et al. (2019) · Nutritional Neuroscience · doi:10.1080/1028415x.2018.1465713 · Cited by 166 · see citing works
High-fat or high-sugar diets as trigger inflammation in the microbiota-gut-brain axis
Jamar, G., Ribeiro, D. A., & Pisani, L. P. (2020) · Critical Reviews in Food Science and Nutrition · doi:10.1080/10408398.2020.1747046 · Cited by 163 · see citing works
Self-citationNeonatal ghrelin programs development of hypothalamic feeding circuits
Steculorum, S. M., Colldén, G., Coupé, B., Croizier, S., Lockie, S. H., Andrews, Z. B., Jarosch, F., Klußmann, S., & Bouret, S. G. (2015) · Journal of Clinical Investigation · doi:10.1172/jci73688 · Cited by 154 · see citing works
Moossavi, S., Miliku, K., Sepehri, S., Khafipour, E., & Azad, M. B. (2018) · Frontiers in Pediatrics · doi:10.3389/fped.2018.00197 · Cited by 154 · see citing works
Ghrelin, a gastrointestinal hormone, regulates energy balance and lipid metabolism
Lv, Y., Liang, T., Wang, G., & Li, Z. (2018) · Bioscience Reports · doi:10.1042/bsr20181061 · Cited by 141 · see citing works
Cortés-Macías, E., Selma‐Royo, M., García‐Mantrana, I., Calatayud, M., González, S., Martínez‐Costa, C., & Collado, M. C. (2020) · Journal of Nutrition · doi:10.1093/jn/nxaa310 · Cited by 140 · see citing works
Ghrelin‐induced adiposity is independent of orexigenic effects
Perez-Tilve, D., Heppner, K., Kirchner, H., Lockie, S. K. H., Woods, S. C., Smiley, D., Tschöp, M., & Pfluger, P. (2011) · The FASEB Journal · doi:10.1096/fj.11-183632 · Cited by 132 · see citing works
Xie, R., Sun, Y., Wu, J., Huang, S., Jin, G., Guo, Z., Zhang, Y., Liu, T., Liu, X., Cao, X., et al. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.02608 · Cited by 126 · see citing works
Nonsaturable entry of neuropeptide Y into brain
Kastin, A. J., & Akerstrom, V. L. (1999) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1999.276.3.e479 · Cited by 119 · see citing works
Heiss, C. N., Mannerås-Holm, L., Lee, Y. S., Serrano-Lobo, J., Håkansson Gladh, A., Seeley, R. J., Drucker, D. J., Bäckhed, F., & Olofsson, L. E. (2021) · Cell Reports · doi:10.1016/j.celrep.2021.109163 · Cited by 114 · see citing works
Region-Specific Neuropeptide Y Overflows at Rest and During Sympathetic Activation in Humans
Morris, M. J., Cox, H. S., Lambert, G. W., Kaye, D. M., Jennings, G., Meredith, I. T., & Esler, M. (1997) · Hypertension · doi:10.1161/01.hyp.29.1.137 · Cited by 107 · see citing works
Zhou, L., & Xiao, X. (2017) · Bioscience Reports · doi:10.1042/bsr20171234 · Cited by 107 · see citing works
Gut peptides and the microbiome: focus on ghrelin
Leeuwendaal, N. K., Cryan, J. F., & Schellekens, H. (2021) · Current Opinion in Endocrinology Diabetes and Obesity · doi:10.1097/med.0000000000000616 · Cited by 103 · see citing works
Gut-Brain Axis in the Early Postnatal Years of Life: A Developmental Perspective
Jena, A., Montoya, C. A., Mullaney, J. A., Dilger, R. N., Young, W., McNabb, W. C., & Roy, N. C. (2020) · Frontiers in Integrative Neuroscience · doi:10.3389/fnint.2020.00044 · Cited by 92 · see citing works
Relationship of maternal high-fat diet during pregnancy and lactation to offspring health
Gawlińska, K., Gawliński, D., Filip, M., & Przegaliński, E. (2020) · Nutrition Reviews · doi:10.1093/nutrit/nuaa020 · Cited by 91 · see citing works
The influence of seminal plasma on offspring development and health
Morgan, H. L., & Watkins, A. J. (2019) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2019.06.008 · Cited by 81 · see citing works
Diet-Induced Modification of the Sperm Epigenome Programs Metabolism and Behavior
Bodden, C., Hannan, A. J., & Reichelt, A. C. (2019) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2019.10.005 · Cited by 80 · see citing works
Impacts of Diet and Exercise on Maternal Gut Microbiota Are Transferred to Offspring
Srinivasan, S. P. B., Raipuria, M., Bahari, H., Kaakoush, N. O., & Morris, M. J. (2018) · Frontiers in Endocrinology · doi:10.3389/fendo.2018.00716 · Cited by 70 · see citing works
The human gut microbiota during the initial stages of life: insights from bifidobacteria
Turroni, F., Milani, C., Ventura, M., & van Sinderen, D. (2021) · Current Opinion in Biotechnology · doi:10.1016/j.copbio.2021.07.012 · Cited by 70 · see citing works
Larson, K., Bundy, A. N., & Roemmich, J. N. (2020) · The Journal of Nutritional Biochemistry · doi:10.1016/j.jnutbio.2020.108373 · Cited by 69 · see citing works
Johnson, S. A., Javurek, A. B., Painter, M. S., Murphy, C. R., Conard, C. M., Gant, K. L., Howald, E. C., Ellersieck, M. R., Wiedmeyer, C. E., Vieira‐Potter, V. J., et al. (2016) · Journal of Developmental Origins of Health and Disease · doi:10.1017/s2040174416000490 · Cited by 54 · see citing works
Wiss, D. A., Criscitelli, K., Gold, M., & Avena, N. (2017) · Appetite · doi:10.1016/j.appet.2016.12.019 · Cited by 53 · see citing works
Raad, G., Serra, F., Martin, L., Derieppe, M., Gilleron, J., Costa, V. L., Pisani, D. F., Amri, E., Trabucchi, M., & Grandjean, V. (2021) · eLife · doi:10.7554/elife.61736 · Cited by 49 · see citing works
Reynolds, C. M., Segovia, S. A., & Vickers, M. H. (2017) · Frontiers in Endocrinology · doi:10.3389/fendo.2017.00245 · Cited by 46 · see citing works
Metabolic responses and benefits of glucagon‐like peptide‐1 (GLP‐1) receptor ligands
Tanday, N., Flatt, P. R., & Irwin, N. (2021) · British Journal of Pharmacology · doi:10.1111/bph.15485 · Cited by 43 · see citing works
Zhang, X., Dong, Y., Sun, G., Hasan, A. A., Tian, M., Zeng, S., Li, J., Zeng, S., Ma, J., Li, J., et al. (2019) · Kidney & Blood Pressure Research · doi:10.1159/000497487 · Cited by 28 · see citing works
Azagra-Boronat, I., Tres, A., Massot‐Cladera, M., Franch, À., Castell, M., Guardiola, F., Pérez-Cano, F. J., & Rodríguez-Lagunas, M. J. (2020) · Nutrients · doi:10.3390/nu12020319 · Cited by 26 · see citing works
Church, J. S., Renzelman, M. L., & Schwartzer, J. J. (2021) · The Journal of Nutritional Biochemistry · doi:10.1016/j.jnutbio.2021.108903 · Cited by 24 · see citing works
César, H., Sertorio, M. N., de Souza, E. A., Jamar, G., Santamarina, A. B., Jucá, A., Casagrande, B. P., & Pisani, L. P. (2021) · European Journal of Nutrition · doi:10.1007/s00394-021-02690-1 · Cited by 18 · see citing works
Self-citationTargeting the Gut in Obesity: Signals from the Inner Surface
Petersen, N., Greiner, T. U., Torz, L., Bookout, A. L., Gerstenberg, M. K., Castorena, C. M., & Kuhre, R. E. (2022) · Metabolites · doi:10.3390/metabo12010039 · Cited by 8 · see citing works
Srivastava, S., & Singh, R. (2021) · Current Research in Nutrition and Food Science Journal · doi:10.12944/crnfsj.9.2.07 · Cited by 6 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Xie, Z., Zhang, M., Luo, Y., Jin, D., Guo, X., Yang, W., Zheng, J., Zhang, H., Zhang, L., Deng, C., et al. (2023) · Aging and disease · doi:10.14336/ad.2023.0309 · Cited by 80 · see citing works
Zhang, Q., Xiao, X., Zheng, J., Li, M., Yu, M., Ping, F., & Wang, T. (2023) · Food & Function · doi:10.1039/d3fo02223d · Cited by 8 · see citing works
Huang, R., Zhou, G.-C., Cai, J., Cao, C., Zhu, Z.-J., Wu, Q.-P., Zhang, F., & Ding, Y. (2025) · Gut microbes · doi:10.1080/19490976.2025.2483783 · Cited by 7 · see citing works
de Almeida, M. M., Calviño, C., Reis-Gomes, C. F., Lombardi, I., Brand, A. L. M., Pazos-Moura, C. C., Garrett, R., Alves, M. A., & Trevenzoli, I. H. (2024) · The Journal of Nutritional Biochemistry · doi:10.1016/j.jnutbio.2024.109802 · Cited by 3 · see citing works
In utero adverse exposures and cardiovascular health in the offspring
Wang, J., Wang, H., Wang, M., Tong, L.-F., Du, B.-W., Yang, T., Wang, B., Wang, X.-W., Xu, Z.-K., Xu, C.-F., et al. (2026) · The Innovation Medicine · doi:10.59717/j.xinn-med.2026.100194 · Cited by 2 · see citing works
de Souza, E. A., Mennitti, L. V., Santamarina, A. B., Jucá, A., Sertorio, M. N., Ferreira, Y. A. M., Minari, T. P., Chen, A. W., Andrade, B. S., & Pisani, L. P. (2025) · Nutrition · doi:10.1016/j.nut.2025.112966 · Cited by 2 · see citing works
Self-citationClarke, G. S., Li, H., Heshmati, E., Gembus, K. M., O’Hara, S. E., Nicholas, L. M., Gatford, K. L., & Page, A. J. (2025) · Experimental Physiology · doi:10.1113/ep093108 · Cited by 1 · see citing works
de Souza, E. A., Mennitti, L. V., Santamarina, A. B., Minari, T. P., Jucá, A., Sertorio, M. N., & Pisani, L. P. (2024) · European Journal of Nutrition · doi:10.1007/s00394-024-03485-w · Cited by 1 · see citing works
Self-citationZazula, M. F., Carvalhal, S. R. S., Maciel, D. T., Moritz, D., Beirauti, H. Y. I., Amorim, L., Rocha, M. T., Maciel, M., Sales, O., Dobgenski, P., et al. (2026) · International Journal of Molecular Sciences · doi:10.3390/ijms27136049
- Authors
- César, H., Nascimento Sertorio, M., Santamarina, A., Alves de Souza, E., Valles Mennitti, L., Jamar, G., Jucá, A., Picin Casagrande, B., Estadela, D., & Pellegrini Pisani, L.
- Affiliations
- Universidade Federal de São Paulo (BR)
- Venue
- Food Research International
- Publisher
- Elsevier BV
- Published
- 2022-10
- Volume
- 160
- Pages
- 111706
- ISSN
- 0963-9969 (ISSN-L)
- OpenAlex
- W4286251158
- Cited by
- 10
- References
- 50
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 3 · 2023: 2
- FWCI
- 0.65
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Food Research International (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Conselho Nacional de Desenvolvimento Cientifico e Tecnologico
- Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (2017/09646-1, 2019/09724-8)
- Coordenação de Aperfeiçoamento de Pessoal de Nível Superior
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Birth, Development, and Health
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Keywords
- gut-brain axis, high-fat high-sugar diet, parental diet, developmental programming, obesity, hypothalamus, colon, TLR4, zonula occludens-1, neuropeptide Y, ghrelin, leptin receptor, MyD88, endotoxemia, lipopolysaccharide, inflammatory cytokines, Bifidobacterium, Lactobacillus, gut microbiota, visceral fat, weaning
- MeSH terms
- Sugars, Brain-Gut Axis, Animals, Female, Humans, Male, Pregnancy, Rats, Wistar, Maternal Nutritional Physiological Phenomena, Rats, Ghrelin, Diet, High-Fat
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
