The DOI matches its Crossref record; 59 of the 60 references it cites were found in a registry or an index.
The Gut Microbiota Reduces Leptin Sensitivity and the Expression of the Obesity-Suppressing Neuropeptides Proglucagon (Gcg) and Brain-Derived Neurotrophic Factor (Bdnf) in the Central Nervous System
Abstract
The gut microbiota contributes to fat mass and the susceptibility to obesity. However, the underlying mechanisms are not completely understood. To investigate whether the gut microbiota affects hypothalamic and brainstem body fat-regulating circuits, we compared gene expression of food intake-regulating neuropeptides between germ-free and conventionally raised (CONV-R) mice. We found that CONV-R mice had decreased expression of the antiobesity neuropeptide glucagon-like peptide-1 (GLP-1) precursor proglucagon (Gcg) in the brainstem. Moreover, in both the hypothalamus and the brainstem, CONV-R mice had decreased expression of the antiobesity neuropeptide brain-derived neurotrophic factor (Bdnf). CONV-R mice had reduced expression of the pro-obesity peptides neuropeptide-Y (Npy) and agouti-related protein (Agrp), and increased expression of the antiobesity peptides proopiomelanocortin (Pomc) and cocaine- and amphetamine-regulated transcript (Cart) in the hypothalamus. The latter changes in neuropeptide expression could be secondary to elevated fat mass in CONV-R mice. Leptin treatment caused less weight reduction and less suppression of orexigenic Npy and Agrp expression in CONV-R mice compared with germ-free mice. The hypothalamic expression of leptin resistance-associated suppressor of cytokine signaling 3 (Socs-3) was increased in CONV-R mice. In conclusion, the gut microbiota reduces the expression of 2 genes coding for body fat-suppressing neuropeptides, Gcg and Bdnf, an alteration that may contribute to fat mass induction by the gut microbiota. Moreover, the presence of body fat-inducing gut microbiota is associated with hypothalamic signs of Socs-3-mediated leptin resistance, which may be linked to failed compensatory body fat reduction.
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“The gut microbiota have been shown to directly moderate brainstem and hypothalamic expression of BDNF, where conventionally raised mice differed significantly from GF mice (Schele et al., 2013).”
From The Microbiota-Gut-Brain Axis (2019) · cites this paper as Schele et al., 2013
In the citing paper
“several studies have demonstrated the significant role of gut microbiome in modulating leptin signaling and adiposity.”
From Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases (2024) · cites this paper as [581]
In the citing paper
“In addition, Schéle et al. [116] found that administration of leptin reduced NPY expression in germ-free mice but not in conventionally raised mice, suggesting that the gut microbiota may decrease leptin sensitivity, effects that are dependent on vagal signaling [192].”
From Anxiety, depression, and the microbiome: A role for gut peptides (2018) · cites this paper as [116]
In the citing paper
“The expression of NPY in the hypothalamus (where NPY plays a major role in feeding behavior and stress response) is increased in adult, healthy, germ-free mice when compared with conventionally raised mice [116].”
From Anxiety, depression, and the microbiome: A role for gut peptides (2018) · cites this paper as [116]
In the citing paper
“Moreover, Schéle et al. [116] demonstrated the role of NPY in counteracting the increased plasma levels of corticosterone in germ-free rodents.”
From Anxiety, depression, and the microbiome: A role for gut peptides (2018) · cites this paper as [116]
Citations
Cites
Positional cloning of the mouse obese gene and its human homologue
Zhang, Y., Proenca, R., Maffei, M., Barone, M., Leopold, L., & Friedman, J. M. (1994) · Nature · doi:10.1038/372425a0 · Cited by 13,419
An obesity-associated gut microbiome with increased capacity for energy harvest
Turnbaugh, P. J., Ley, R. E., Mahowald, M. A., Magrini, V., Mardis, E. R., & Gordon, J. I. (2006) · Nature · doi:10.1038/nature05414 · Cited by 12,444
A core gut microbiome in obese and lean twins
Turnbaugh, P. J., Hamady, M., Yatsunenko, T., Cantarel, B. L., Duncan, A., Ley, R. E., Sogin, M. L., Jones, W. J., Roe, B. A., Affourtit, J. P., et al. (2009) · Nature · doi:10.1038/nature07540 · Cited by 7,823
Metabolic Endotoxemia Initiates Obesity and Insulin Resistance
Cani, P. D., Amar, J., Iglesias, M. A., Poggi, M., Knauf, C., Bastelica, D., Neyrinck, A. M., Fava, F., Tuohy, K. M., Chabo, C., et al. (2007) · Diabetes · doi:10.2337/db06-1491 · Cited by 6,638
Central nervous system control of food intake
Schwartz, M. W., Woods, S. C., Porte, D., Seeley, R. J., & Baskin, D. G. (2000) · Nature · doi:10.1038/35007534 · Cited by 6,451
Serum Immunoreactive-Leptin Concentrations in Normal-Weight and Obese Humans
Considine, R. V., Sinha, M. K., Heiman, M. L., Kriauciunas, A., Stephens, T. W., Nyce, M. R., Ohannesian, J. P., Marco, C. C., McKee, L. J., Bauer, T. L., et al. (1996) · New England Journal of Medicine · doi:10.1056/nejm199602013340503 · Cited by 6,326
The gut microbiota as an environmental factor that regulates fat storage
Bäckhed, F., Ding, H., Wang, T., Hooper, L. V., Koh, G. Y., Nagy, A., Semenkovich, C. F., & Gordon, J. I. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0407076101 · Cited by 6,245
Self-citationCani, P. D., Bibiloni, R., Knauf, C., Waget, A., Neyrinck, A. M., Delzenne, N. M., & Burcelin, R. (2008) · Diabetes · doi:10.2337/db07-1403 · Cited by 4,819
Normal gut microbiota modulates brain development and behavior
Heijtz, R. D., Wang, S., Anuar, F., Qian, Y., Björkholm, B., Samuelsson, A., Hibberd, M. L., Forssberg, H., & Pettersson, S. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1010529108 · Cited by 3,228
Targeted disruption of the melanocortin-4 receptor results in obesity in mice
Huszar, D., Lynch, C. A., Fairchild-Huntress, V., Dunmore, J. H., Fang, Q., Berkemeier, L. R., Gu, W., Kesterson, R. A., Boston, B. A., Cone, R. D., et al. (1997) · Cell · doi:10.1016/s0092-8674(00)81865-6 · Cited by 3,030
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Chai, H., & Lee, S. (2025) · Current Topic in Lactic Acid Bacteria and Probiotics · doi:10.35732/ctlabp.2025.11.2.50 · Cited by 2
Holzer, P. D., & Farzi, A. (2019) · Elsevier eBooks · doi:10.1016/b978-0-443-13825-6.00401-5
Martínez-Ruiz, M., Tabor‐Simecka, L., Graham, J. L., Randolph, C., Fox, R., Lan, R. S.-L., Pack, L., LeRoith, T., Stanhope, K. L., Yeruva, L., et al. (2026) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00412.2025
Pocheron, A.-L. (2019) · theses.fr (ABES) · doi:10.70675/29969b86z2649z4b67zb315za23a1106f4ef
Metabolic Roles of Acyl Coenzyme A-Binding Protein (ACBP)/Diazepam Binding Inhibitor (DBI)
Joseph, A. (2021) · theses.fr (ABES) · doi:10.70675/b045685ezd444z4b46zb0f9z0e726ceac466
Roussin, L. (2023) · theses.fr (ABES) · doi:10.70675/998d3bd1z4618z400dz998cz89e524b35aef · Cited by 1
The Microbiota–Gut–Brain Axis in Obesity: Inflammation, Appetite Dysregulation, and Feeding Behavior
Sandoval-Valenzuela, C., & Pacheco, R. (2026) · Nutrients · doi:10.3390/nu18203409
Glenn, E., Titus, C., Kasthuriarachchi, T. D. W., Burke, K., Chow, D., Lin, C., Liu, E., Zhang, H., Zhang, T., & Li, Y. (2026) · Journal of Pharmaceutical Sciences · doi:10.1016/j.xphs.2026.104509
Metadata
- Authors
- Schéle, E., Grahnemo, L., Anesten, F., Hallén, A., Bäckhed, F., & Jansson, J.-O.
- Affiliations
- University of Gothenburg (SE)
- University of Copenhagen (DK)
- Corresponding author
- Jansson, John-Olov
- Venue
- Endocrinology
- Publisher
- The Endocrine Society
- Published
- 2013-10-01
- Volume
- 154
- Issue
- 10
- Pages
- 3643-3651
- ISSN
- 0013-7227 (ISSN-L)
- 1945-7170
- OpenAlex
- W2013890677
- Cited by
- 209
- References
- 60
- Citations by year
- 2026: 7 · 2025: 15 · 2024: 19 · 2023: 19 · 2022: 18 · 2021: 24 · 2020: 11 · 2019: 19 · 2018: 15 · 2017: 13 · 2016: 20 · 2015: 16 · 2014: 12 · 2013: 1
- FWCI
- 8.80
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Endocrinology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Vetenskapsrådet
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
- Keywords
- gut microbiota, leptin resistance, proglucagon, brain-derived neurotrophic factor, obesity, hypothalamus, brainstem, neuropeptides, germ-free mice, SOCS3, neuropeptide Y, agouti-related protein, proopiomelanocortin, cocaine- and amphetamine-regulated transcript, food intake regulation, fat mass
- MeSH terms
- Suppressor of Cytokine Signaling 3 Protein, Cocaine- and Amphetamine-Regulated Transcript Protein, Animals, Brain Stem, Central Nervous System, Germ-Free Life, Hypothalamus, Injections, Intraperitoneal, Intestines, Male, Mice, Inbred C57BL, Nerve Tissue Proteins, Neurons, Neuropeptide Y, Pro-Opiomelanocortin, Recombinant Proteins, Down-Regulation, Brain-Derived Neurotrophic Factor, Leptin, Adiposity, Suppressor of Cytokine Signaling Proteins, Mice, Proglucagon, Agouti-Related Protein
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