Duodenal Lipid Sensing Activates Vagal Afferents to Regulate Non-Shivering Brown Fat Thermogenesis in Rats
Open accessAbstract
Previous evidence indicates that duodenal lipid sensing engages gut-brain neurocircuits to determine food intake and hepatic glucose production, but a potential role for gut-brain communication in the control of energy expenditure remains to be determined. Here, we tested the hypothesis that duodenal lipid sensing activates a gut-brain-brown adipose tissue neuraxis to regulate thermogenesis. We demonstrate that direct administration of lipids into the duodenum increases brown fat temperature. Co-infusion of the local anesthetic tetracaine with duodenal lipids abolished the lipid-induced increase in brown fat temperature. Systemic administration of the CCKA receptor antagonist devazepide blocked the ability of duodenal lipids to increase brown fat thermogenesis. Parenchymal administration of the N-methyl-d-aspartate receptor blocker MK-801 directly into the caudomedial nucleus of the solitary tract also abolished duodenal lipid-induced activation of brown fat thermogenesis. These findings establish that duodenal lipid sensing activates a gut-brain-brown fat axis to determine brown fat temperature, and thereby reveal a previously unappreciated pathway that regulates thermogenesis.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
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?
Feeding activates the secretion of periprandial gut hormones, such as CCK, GLP‐1, or secretin.
“In particular, feeding activates the secretion of periprandial gut hormones, such as CCK, GLP‐1, or secretin 105, 106, 107.”
From Inter‐organ communication: a gatekeeper for metabolic health (2019) · cites this paper as [106]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
1 retracted
Sabbatini, M., Molinari, C., Grossini, E., et al. (2008) · Neuroscience · doi:10.1016/j.neuroscience.2008.01.008 · Cited by 5 · see citing works
RetractedIdentification and Importance of Brown Adipose Tissue in Adult Humans
Cypess, A. M., Lehman, S., Williams, G., Tal, I., Rodman, D., Goldfine, A. B., Kuo, F. C., Palmer, E. L., Tseng, Y.-H., Doria, A., et al. (2009) · New England Journal of Medicine · doi:10.1056/nejmoa0810780 · Cited by 4,399 · see citing works
Cold-Activated Brown Adipose Tissue in Healthy Men
van Marken Lichtenbelt, W. D., Vanhommerig, J. W., Smulders, N. M., Drossaerts, J. M. A. F. L., Kemerink, G. J., Bouvy, N. D., Schrauwen, P., & Teule, G. J. J. (2009) · New England Journal of Medicine · doi:10.1056/nejmoa0808718 · Cited by 3,452 · see citing works
Functional Brown Adipose Tissue in Healthy Adults
Virtanen, K. A., Lidell, M. E., Orava, J., Heglind, M., Westergren, R., Niemi, T., Taittonen, M., Laine, J., Savisto, N.-J., Enerbäck, S., et al. (2009) · New England Journal of Medicine · doi:10.1056/nejmoa0808949 · Cited by 3,058 · see citing works
Towards a molecular understanding of adaptive thermogenesis
Lowell, B. B., & Spiegelman, B. M. (2000) · Nature · doi:10.1038/35007527 · Cited by 1,630 · see citing works
Proopiomelanocortin Neurons Are Direct Targets for Leptin in the Hypothalamus
Cheung, C. C., Clifton, D. K., & Steiner, R. A. (1997) · Endocrinology · doi:10.1210/endo.138.10.5570 · Cited by 769 · cited 1× · see citing works
“Prior studies demonstrated that intestinal infusions of MK329 were sufficient to block the ability of duodenal CCK to inhibit hepatic glucose production [36], but these studies did not preclude the possibility that the MK329 acted outside the lumen, at other peripheral or central CCKA receptor sites.”
BackgroundWesterterp, K. R. (2004) · Nutrition & Metabolism · doi:10.1186/1743-7075-1-5 · Cited by 570 · see citing works
CNS origins of the sympathetic nervous system outflow to brown adipose tissue
Bamshad, M., Song, C. K., & Bartness, T. J. (1999) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.1999.276.6.r1569 · Cited by 437 · see citing works
Upper intestinal lipids trigger a gut–brain–liver axis to regulate glucose production
Wang, P. Y. T., Caspi, L., Lam, C., Chari, M., Li, X., Light, P. E., Juárez, R. G., Ang, M. L. T., Schwartz, G. J., & Lam, T. K. T. (2008) · Nature · doi:10.1038/nature06852 · Cited by 293 · see citing works
Self-citationLocalization of hindbrain glucoreceptive sites controlling food intake and blood glucose
Ritter, S., Dinh, T. T., & Zhang, Y. (2000) · Brain Research · doi:10.1016/s0006-8993(99)02327-6 · Cited by 263 · see citing works
Diet-induced thermogenesis measured over a whole day in obese and nonobese women
Schütz, Y., Bessard, T., & Jéquier, E. (1984) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/40.3.542 · Cited by 261 · see citing works
Central and peripheral vagal transport of cholecystokinin binding sites occurs in afferent fibers
Moran, T. H., Norgren, R., Crosby, R. J., & McHugh, P. R. (1990) · Brain Research · doi:10.1016/0006-8993(90)90253-8 · Cited by 187 · see citing works
Mönnikes, H., Lauer, G., & Arnold, R. (1997) · Brain Research · doi:10.1016/s0006-8993(97)00865-2 · Cited by 172 · see citing works
Capsaicin attenuates suppression of sham feeding induced by intestinal nutrients
Yox, D. P., & Ritter, R. C. (1988) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.1988.255.4.r569 · Cited by 160 · see citing works
Brainstem Nutrient Sensing in the Nucleus of the Solitary Tract Inhibits Feeding
Blouet, C., & Schwartz, G. J. (2012) · Cell Metabolism · doi:10.1016/j.cmet.2012.10.003 · Cited by 145 · see citing works
Self-citationExpenditure and storage of energy in man.
Sims, E. A. H., & Danforth, E. (1987) · Journal of Clinical Investigation · doi:10.1172/jci112913 · Cited by 140 · see citing works
Aicher, S. A., Sharma, S., & Pickel, V. M. (1999) · Neuroscience · doi:10.1016/s0306-4522(98)00530-2 · Cited by 134 · see citing works
Berthoud, H. R., & Patterson, L. M. (1996) · Cells Tissues Organs · doi:10.1159/000147837 · Cited by 125 · see citing works
Inhibition of food intake in response to intestinal lipid is mediated by cholecystokinin in humans
Matzinger, D., Gutzwiller, J., Drewe, J., Orban, A., Engel, R., D’Amato, M., Rovati, L. C., & Beglinger, C. (1999) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.1999.277.6.r1718 · Cited by 122 · see citing works
Skibicka, K. P., & Grill, H. J. (2009) · Endocrinology · doi:10.1210/en.2009-0804 · Cited by 113 · see citing works
Mönnikes, H., Lauer, G., Bauer, C., Tebbe, J. J., Zittel, T. T., & Arnold, R. (1997) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.1997.273.6.r2059 · Cited by 113 · see citing works
Madden, C. J., & Morrison, S. F. (2005) · The Journal of Physiology · doi:10.1113/jphysiol.2005.086322 · Cited by 105 · see citing works
Intraduodenal infusions of fats elicit satiety in sham-feeding rats
Greenberg, D., Smith, G. P., & Gibbs, J. (1990) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.1990.259.1.r110 · Cited by 105 · see citing works
Schwartz, G. J., Whitney, A. C., Skoglund, C., Castonguay, T. W., & Moran, T. H. (1999) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.1999.277.4.r1144 · Cited by 101 · see citing works
Self-citationCao, W.-H., Madden, C. J., & Morrison, S. F. (2010) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00039.2010 · Cited by 85 · see citing works
Sympathetic premotor neurons mediating thermoregulatory functions
Nakamura, K., Matsumura, K., Kobayashi, S., & Kaneko, T. (2004) · Neuroscience Research · doi:10.1016/j.neures.2004.09.007 · Cited by 81 · see citing works
Plasma secretin, CCK, and pancreatic secretion in response to dietary fat in the rat
Green, G. M., Taguchi, S., Friestman, J., et al. (1989) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.1989.256.6.g1016 · Cited by 79 · see citing works
Duodenal nutrient infusions differentially affect sham feeding and Fos expression in rat brain stem
Phifer, C. B., & Berthoud, H. (1998) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.1998.274.6.r1725 · Cited by 68 · see citing works
Berthoud, H., Earle, T., Zheng, H., Patterson, L. M., & Phifer, C. (2001) · Brain Research · doi:10.1016/s0006-8993(01)02826-8 · Cited by 66 · see citing works
Brenner, L., Yox, D. P., & Ritter, R. C. (1993) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.1993.264.5.r972 · Cited by 66 · see citing works
Wright, J. S., Campos, C., Herzog, T., Covașă, M., Czaja, K., & Ritter, R. C. (2011) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00026.2011 · Cited by 53 · see citing works
Rasmussen, B. A., Breen, D. M., Luo, P., Cheung, G. W. C., Yang, C. S., Sun, B., Kokorovic, A., Rong, W., & Lam, T. K. T. (2012) · Gastroenterology · doi:10.1053/j.gastro.2011.12.053 · Cited by 49 · see citing works
Reidelberger, R. D., Heimann, D. G., Kelsey, L. S., & Hulce, M. (2003) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00529.2002 · Cited by 49 · see citing works
Campos, C., Wright, J. S., Czaja, K., & Ritter, R. C. (2012) · Endocrinology · doi:10.1210/en.2012-1025 · Cited by 48 · see citing works
Czaja, K., Ritter, R. C., & Burns, G. A. (2006) · Brain Research · doi:10.1016/j.brainres.2006.08.042 · Cited by 36 · see citing works
Shibata, H., & Bukowiecki, L. J. (1987) · Journal of Applied Physiology · doi:10.1152/jappl.1987.63.2.465 · Cited by 34 · see citing works
Guard, D. B., Swartz, T. D., Ritter, R. C., et al. (2009) · Brain Research · doi:10.1016/j.brainres.2009.02.003 · Cited by 33 · see citing works
Intestinal capsaicin transiently attenuates suppression of sham feeding by oleate
Tamura, C. S., & Ritter, R. C. (1994) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.1994.267.2.r561 · Cited by 23 · see citing works
Decreased Incidence of Tourniquet Pain During Spinal Anesthesia with Bupivacaine
Stewart, A., Lambert, D. H., Concepcion, M. A., et al. (1989) · Survey of Anesthesiology · doi:10.1097/00132586-198902000-00045 · Cited by 18 · see citing works
Stewart, A., Lambert, D. H., Concepcion, M. A., et al. (1988) · Anesthesia & Analgesia · doi:10.1213/00000539-198809000-00006 · Cited by 16 · see citing works
Kang, Y. H., Sun, B., Park, Y. S., Park, C.-S., & Jin, Y.-H. (2012) · Neuroscience · doi:10.1016/j.neuroscience.2012.02.025 · Cited by 9 · see citing works
Regional Variations in Responses of Rat GI Tract to Local Anesthetics
Tansy, M. F., & Ganse, G. (1972) · Journal of Pharmaceutical Sciences · doi:10.1002/jps.2600610723 · Cited by 8 · see citing works
Dinda, P. K., & Beck, I. T. (1969) · Canadian Journal of Physiology and Pharmacology · doi:10.1139/y69-079 · Cited by 3 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Role of the gut-brain axis in energy and glucose metabolism
Wachsmuth, H. R., Weninger, S. N., & Duca, F. A. (2022) · Experimental & Molecular Medicine · doi:10.1038/s12276-021-00677-w · Cited by 269 · see citing works
Secretin-Activated Brown Fat Mediates Prandial Thermogenesis to Induce Satiation
Li, Y., Schnabl, K., Gabler, S.-M., Willershäuser, M., Reber, J., Karlas, A., Laurila, S., Lahesmaa, M., u Din, M., Bast-Habersbrunner, A., et al. (2018) · Cell · doi:10.1016/j.cell.2018.10.016 · Cited by 228 · see citing works
Inter‐organ communication: a gatekeeper for metabolic health
Castillo‐Armengol, J., Fajas, L., & Lopez‐Mejia, I. C. (2019) · The EMBO Reports · doi:10.15252/embr.201947903 · Cited by 178 · see citing works
Brain regulation of energy balance and body weight
Rui, L. (2013) · Reviews in Endocrine and Metabolic Disorders · doi:10.1007/s11154-013-9261-9 · Cited by 168 · see citing works
McDougle, M., Quinn, D., Diepenbroek, C., Singh, A., de la Serre, C., & de Lartigue, G. (2021) · Acta Physiologica · doi:10.1111/apha.13530 · Cited by 42 · see citing works
- Authors
- Blouet, C., & Schwartz, G. J.
- Affiliations
- Albert Einstein College of Medicine (US)
- Corresponding author
- Schwartz, Gary J.
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2012-12-14
- Volume
- 7
- Issue
- 12
- Pages
- e51898
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC3522613
- OpenAlex
- W1999624003
- Cited by
- 81
- References
- 43
- Citations by year
- 2025: 2 · 2024: 5 · 2023: 7 · 2022: 6 · 2021: 4 · 2020: 9 · 2019: 8 · 2018: 9 · 2017: 6 · 2016: 8 · 2015: 7 · 2014: 8 · 2013: 2
- FWCI
- 3.65
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PLoS ONE (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Funders
- National Institutes of Health (5r01dk026667-13, DK 020541)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK026667, DK-020541, P60DK020541, P30DK020541)
- Topics
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
- Keywords
- vagal afferents, gut-brain signaling, CCK-A receptor, devazepide, NMDA receptor, MK-801, tetracaine, energy expenditure, brown adipose tissue
- MeSH terms
- Animals, Body Temperature Regulation, Adipose Tissue, Brown, Duodenum, Eating, Neurons, Afferent, Sensory Receptor Cells, Vagus Nerve, Dizocilpine Maleate, Rats, Sprague-Dawley, Devazepide, Thermogenesis, Lipid Metabolism, Rats
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
