Loss of dorsomedial hypothalamic GLP-1 signaling reduces BAT thermogenesis and increases adiposity
Open accessAbstract
OBJECTIVE: Glucagon-like peptide-1 (GLP-1) neurons in the hindbrain densely innervate the dorsomedial hypothalamus (DMH), a nucleus strongly implicated in body weight regulation and the sympathetic control of brown adipose tissue (BAT) thermogenesis. Therefore, DMH GLP-1 receptors (GLP-1R) are well placed to regulate energy balance by controlling sympathetic outflow and BAT function. METHODS: We investigate this possibility in adult male rats by using direct administration of GLP-1 (0.5 ug) into the DMH, knocking down DMH GLP-1R mRNA with viral-mediated RNA interference, and by examining the neurochemical phenotype of GLP-1R expressing cells in the DMH using in situ hybridization. RESULTS: GLP-1 administered into the DMH increased BAT thermogenesis and hepatic triglyceride (TG) mobilization. On the other hand, Glp1r knockdown (KD) in the DMH increased body weight gain and adiposity, with a concomitant reduction in energy expenditure (EE), BAT temperature, and uncoupling protein 1 (UCP1) expression. Moreover, DMH Glp1r KD induced hepatic steatosis, increased plasma TG, and elevated liver specific de-novo lipogenesis, effects that collectively contributed to insulin resistance. Interestingly, DMH Glp1r KD increased neuropeptide Y (NPY) mRNA expression in the DMH. GLP-1R mRNA in the DMH, however, was found in GABAergic not NPY neurons, consistent with a GLP-1R-dependent inhibition of NPY neurons that is mediated by local GABAergic neurons. Finally, DMH Glp1r KD attenuated the anorexigenic effects of the GLP-1R agonist exendin-4, highlighting an important role of DMH GLP-1R signaling in GLP-1-based therapies. CONCLUSIONS: Collectively, our data show that DMH GLP-1R signaling plays a key role for BAT thermogenesis and adiposity.
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?
The DMH plays a pivotal role in long-term metabolic regulation including energy expenditure, thermogenesis, and circadian rhythm.
“The DMH plays a pivotal role in long-term metabolic regulation, including energy expenditure, thermogenesis, and circadian rhythm (27–29).”
From GLP-1 increases preingestive satiation via hypothalamic circuits in mice and humans (2024) · cites this paper as [27]
Administration of GLP-1 in the DMH increases BAT thermogenesis.
“Similarly, administration of the incretin hormone GLP‐1 in the DMH increases BAT thermogenesis 82.”
From Inter‐organ communication: a gatekeeper for metabolic health (2019) · cites this paper as [82]
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
Neural regulation of endocrine and autonomic stress responses
Ulrich-Lai, Y. M., & Herman, J. P. (2009) · Nature Reviews Neuroscience · doi:10.1038/nrn2647 · Cited by 3,318 · 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
A Randomized, Controlled Trial of 3.0 mg of Liraglutide in Weight Management
Pi-Sunyer, X., Astrup, A., Fujioka, K., Greenway, F., Halpern, A., Krempf, M., Lau, D. C. W., le Roux, C. W., Violante Ortiz, R., Jensen, C. B., et al. (2015) · New England Journal of Medicine · doi:10.1056/nejmoa1411892 · Cited by 2,724 · see citing works
Brown adipose tissue activity controls triglyceride clearance
Bartelt, A., Bruns, O. T., Reimer, R., Hohenberg, H., Ittrich, H., Peldschus, K., Kaul, M. G., Tromsdorf, U. I., Weller, H., Waurisch, C., et al. (2011) · Nature Medicine · doi:10.1038/nm.2297 · Cited by 1,608 · cited 1× · see citing works
“Although we cannot rule out the possibility that Glp1r KD directly affected hepatic glucose metabolism via an NPYdependent pathway, defective BAT function may be the primary underlying cause of energy imbalance and insulin resistance as its normal function is important for the clearance of glucose and triglycerides fr…”
BackgroundBrown adipose tissue regulates glucose homeostasis and insulin sensitivity
Stanford, K. I., Middelbeek, R. J. W., Townsend, K. L., An, D., Nygaard, E. B., Hitchcox, K. M., Markan, K. R., Nakano, K., Hirshman, M. F., Tseng, Y.-H., et al. (2013) · Journal of Clinical Investigation · doi:10.1172/jci62308 · Cited by 1,180 · see citing works
The arcuate nucleus mediates GLP-1 receptor agonist liraglutide-dependent weight loss
Secher, A., Jelsing, J., Baquero, A. F., Hecksher-Sørensen, J., Cowley, M. A., Dalbøge, L. S., Hansen, G., Grove, K. L., Pyke, C., Raun, K., et al. (2014) · Journal of Clinical Investigation · doi:10.1172/jci75276 · Cited by 961 · see citing works
Imaging of neutral lipids by oil red O for analyzing the metabolic status in health and disease
Mehlem, A., Hagberg, C. E., Muhl, L., Eriksson, U., & Falkevall, A. (2013) · Nature Protocols · doi:10.1038/nprot.2013.055 · Cited by 897 · see citing works
A guide to analysis of mouse energy metabolism
Tschöp, M. H., Speakman, J. R., Arch, J. R. S., Auwerx, J., Brüning, J. C., Chan, L., Eckel, R. H., Farese, R. V., Galgani, J. E., Hambly, C., et al. (2012) · Nature Methods · doi:10.1038/nmeth.1806 · Cited by 813 · see citing works
Drucker, D. J. (1998) · Diabetes · doi:10.2337/diab.47.2.159 · Cited by 602 · see citing works
GLP-1 agonism stimulates brown adipose tissue thermogenesis and browning through hypothalamic AMPK
Beiroa, D., Imbernon, M., Gallego, R., Senra, A., Herranz, D., Villarroya, F., Serrano, M., Fernø, J., Salvador, J., Escalada, J., et al. (2014) · Diabetes · doi:10.2337/db14-0302 · Cited by 602 · see citing works
Hany, T. F., Gharehpapagh, E., Kamel, E. M., Buck, A., Himms-Hagen, J., & von Schulthess, G. K. (2002) · European Journal of Nuclear Medicine and Molecular Imaging · doi:10.1007/s00259-002-0902-6 · Cited by 511 · see citing works
Cork, S. C., Richards, J. E., Holt, M. K., Gribble, F. M., Reimann, F., & Trapp, S. (2015) · Molecular Metabolism · doi:10.1016/j.molmet.2015.07.008 · Cited by 478 · 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
Unraveling the Regulation of Hepatic Metabolism by Insulin
Titchenell, P. M., Lazar, M. A., & Birnbaum, M. J. (2017) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2017.03.003 · Cited by 434 · see citing works
Central Neural Regulation of Brown Adipose Tissue Thermogenesis and Energy Expenditure
Morrison, S. F., Madden, C. J., & Tupone, D. (2014) · Cell Metabolism · doi:10.1016/j.cmet.2014.02.007 · Cited by 427 · see citing works
Neuronal GLP1R mediates liraglutide’s anorectic but not glucose-lowering effect
Sisley, S. R., Gutiérrez‐Aguilar, R., Scott, M. M., D’Alessio, D. A., Sandoval, D. A., & Seeley, R. J. (2014) · Journal of Clinical Investigation · doi:10.1172/jci72434 · Cited by 394 · see citing works
Baggio, L. L., Huang, Q., Brown, T. J., & Drucker, D. J. (2004) · Gastroenterology · doi:10.1053/j.gastro.2004.04.063 · Cited by 372 · see citing works
Kanoski, S. E., Fortin, S. M., Arnold, M., Grill, H. J., & Hayes, M. R. (2011) · Endocrinology · doi:10.1210/en.2011-0174 · Cited by 347 · see citing works
Self-citationLeptin Mediates the Increase in Blood Pressure Associated with Obesity
Simonds, S. E., Pryor, J. T., Ravussin, É., Greenway, F. L., Dileone, R., Allen, A. M., Bassi, J. K., Elmquist, J. K., Keogh, J. M., Henning, E., et al. (2014) · Cell · doi:10.1016/j.cell.2014.10.058 · Cited by 347 · see citing works
Panjwani, N., Mulvihill, E. E., Longuet, C., Yusta, B., Campbell, J. E., Brown, T. J., Streutker, C., Holland, D., Cao, X., Baggio, L. L., et al. (2013) · Endocrinology · doi:10.1210/en.2012-1937 · Cited by 346 · see citing works
Cano, G., Passerin, A. M., Schiltz, J. C., Card, J. P., Morrison, S. F., & Sved, A. F. (2003) · The Journal of Comparative Neurology · doi:10.1002/cne.10643 · Cited by 337 · see citing works
Brown fat fuel utilization and thermogenesis
Townsend, K. L., & Tseng, Y. (2014) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2013.12.004 · Cited by 332 · see citing works
Enriori, P. J., Sinnayah, P., Simonds, S. E., Rudaz, C. G., & Cowley, M. A. (2011) · Journal of Neuroscience · doi:10.1523/jneurosci.2336-11.2011 · Cited by 318 · see citing works
Oldfield, B. J., Giles, M., Watson, A. M. D., Anderson, C. R., Colvill, L. M., & McKinley, M. J. (2002) · Neuroscience · doi:10.1016/s0306-4522(01)00555-3 · Cited by 317 · see citing works
Arcuate Glucagon-Like Peptide 1 Receptors Regulate Glucose Homeostasis but Not Food Intake
Sandoval, D. A., Bagnol, D., Woods, S. C., D’Alessio, D. A., & Seeley, R. J. (2008) · Diabetes · doi:10.2337/db07-1824 · Cited by 316 · see citing works
Central Mechanisms Underlying Short‐ And Long‐Term Regulation Of The Cardiovascular System
Dampney, R. A. L., Coleman, M., Fontes, M., Hirooka, Y., Horiuchi, J., Li, Y. W., Polson, J. W., Potts, P. D., & Tagawa, T. (2002) · Clinical and Experimental Pharmacology and Physiology · doi:10.1046/j.1440-1681.2002.03640.x · Cited by 315 · see citing works
Knauf, C. (2005) · Journal of Clinical Investigation · doi:10.1172/jci25764 · Cited by 310 · see citing works
Yamamoto, H., Kishi, T., Lee, C. E., Choi, B. J., Fang, H., Hollenberg, A. N., Drucker, D. J., & Elmquist, J. K. (2003) · The Journal of Neuroscience · doi:10.1523/jneurosci.23-07-02939.2003 · Cited by 294 · see citing works
Paradoxical resistance to diet-induced obesity in UCP1-deficient mice
Liu, X., Rossmeisl, M., McClaine, J. W., & Kozak, L. P. (2003) · Journal of Clinical Investigation · doi:10.1172/jci200315737 · Cited by 281 · see citing works
Neuropeptide Y suppresses sympathetic activity to interscapular brown adipose tissue in rats
Egawa, M., Yoshimatsu, H., & Bray, G. A. (1991) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.1991.260.2.r328 · Cited by 272 · see citing works
Shi, Y.-C., Lau, J., Lin, Z., Zhang, H., Zhai, L., Sperk, G., Heilbronn, R., Mietzsch, M., Weger, S., Huang, X.-F., et al. (2013) · Cell Metabolism · doi:10.1016/j.cmet.2013.01.006 · Cited by 266 · see citing works
Paradoxical resistance to diet-induced obesity in UCP1-deficient mice
Liu, X., Rossmeisl, M., McClaine, J. W., & Kozak, L. P. (2003) · Journal of Clinical Investigation · doi:10.1172/jci15737 · Cited by 265 · see citing works
Rüttimann, E. B., Arnold, M., Hillebrand, J. J., Geary, N., & Langhans, W. (2008) · Endocrinology · doi:10.1210/en.2008-1221 · Cited by 258 · see citing works
Self-citationGlucagonlike peptide 1: a newly discovered gastrointestinal hormone
Holst, J. J. (1994) · Gastroenterology · doi:10.1016/0016-5085(94)90831-1 · Cited by 252 · see citing works
Esclapez, M., Tillakaratne, N. J. K., Tobin, A. J., & Houser, C. R. (1993) · The Journal of Comparative Neurology · doi:10.1002/cne.903310305 · Cited by 251 · see citing works
Distribution of vesicular glutamate transporter mRNA in rat hypothalamus
Ziegler, D. R., Cullinan, W. E., & Herman, J. P. (2002) · Journal of Comparative Neurology · doi:10.1002/cne.10257 · Cited by 241 · see citing works
Zhang, Y., Kerman, I. A., Laque, A., Nguyen, P., Faouzi, M., Louis, G. W., Jones, J. C., Rhodes, C. J., & Münzberg, H. (2011) · Journal of Neuroscience · doi:10.1523/jneurosci.3223-10.2011 · Cited by 240 · see citing works
Kataoka, N., Hioki, H., Kaneko, T., & Nakamura, K. (2014) · Cell Metabolism · doi:10.1016/j.cmet.2014.05.018 · Cited by 240 · see citing works
Lockie, S. H., Heppner, K. M., Chaudhary, N., Chabenne, J. R., Morgan, D. A., Veyrat‐Durebex, C., Ananthakrishnan, G., Rohner‐Jeanrenaud, F., Drucker, D. J., DiMarchi, R. D., et al. (2012) · Diabetes · doi:10.2337/db11-1556 · Cited by 238 · see citing works
Even, P. C., & Nadkarni, N. A. (2012) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00137.2012 · Cited by 237 · see citing works
The dorsomedial hypothalamic nucleus and its role in ingestive behavior and body weight regulation
Bellinger, L. L., & Bernardis, L. L. (2002) · Physiology & Behavior · doi:10.1016/s0031-9384(02)00756-4 · Cited by 228 · see citing works
Cao, W.-H., Fan, W., & Morrison, S. F. (2004) · Neuroscience · doi:10.1016/j.neuroscience.2004.03.013 · Cited by 221 · see citing works
Chao, P.-T., Yang, L., Aja, S. M., Moran, T. H., & Bi, S. (2011) · Cell Metabolism · doi:10.1016/j.cmet.2011.02.019 · Cited by 206 · see citing works
Kesterson, R. A., Huszar, D., Lynch, C. A., Simerly, R. B., & Cone, R. D. (1997) · Molecular Endocrinology · doi:10.1210/mend.11.5.9921 · Cited by 205 · see citing works
Preproglucagon neurons project widely to autonomic control areas in the mouse brain
Llewellyn-Smith, I. J., Reimann, F., Gribble, F. M., & Trapp, S. (2011) · Neuroscience · doi:10.1016/j.neuroscience.2011.02.023 · Cited by 194 · see citing works
Rezai-Zadeh, K. P., Yu, S., Jiang, Y., Laque, A., Schwartzenburg, C., Morrison, C. D., Derbenev, A. V., Zsombok, A., & Münzberg, H. (2014) · Molecular Metabolism · doi:10.1016/j.molmet.2014.07.008 · Cited by 193 · see citing works
Central Control of Brown Adipose Tissue Thermogenesis
Morrison, S. F., Madden, C. J., & Tupone, D. (2012) · Frontiers in Endocrinology · doi:10.3389/fendo.2012.00005 · Cited by 189 · see citing works
The central GLP-1: implications for food and drug reward
Skibicka, K. P. (2013) · Frontiers in Neuroscience · doi:10.3389/fnins.2013.00181 · Cited by 188 · see citing works
Nogueiras, R., Pérez-Tilve, D., Veyrat-Durebex, C., Morgan, D. A., Varela, L., Haynes, W. G., Patterson, J. T., Disse, E., Pfluger, P. T., López, M., et al. (2009) · The Journal of Neuroscience · doi:10.1523/jneurosci.5977-08.2009 · Cited by 182 · see citing works
Leptin Regulation of the Anorexic Response to Glucagon-Like Peptide-1 Receptor Stimulation
Williams, D. L., Baskin, D. G., & Schwartz, M. W. (2006) · Diabetes · doi:10.2337/db06-0558 · Cited by 178 · see citing works
Zaretskaia, M. V., Zaretsky, D. V., Shekhar, A., & DiMicco, J. A. (2002) · Brain Research · doi:10.1016/s0006-8993(01)03369-8 · Cited by 173 · see citing works
The Implication of Brown Adipose Tissue for Humans
Ravussin, É., & Galgani, J. E. (2011) · Annual Review of Nutrition · doi:10.1146/annurev-nutr-072610-145209 · Cited by 166 · see citing works
Swanson, L. W., Sanchez‐Watts, G., & Watts, A. G. (2005) · Neuroscience Letters · doi:10.1016/j.neulet.2005.06.066 · Cited by 149 · see citing works
Self-citationSchmidt, H. D., Mietlicki-Baase, E. G., Ige, K. Y., Maurer, J. J., Reiner, D. J., Zimmer, D. J., Van Nest, D. S., Guercio, L. A., Wimmer, M. E., Olivos, D. R., et al. (2016) · Neuropsychopharmacology · doi:10.1038/npp.2015.362 · Cited by 148 · see citing works
Self-citationMadden, C. J., & Morrison, S. F. (2009) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.91007.2008 · Cited by 140 · see citing works
Kooijman, S., Wang, Y., Parlevliet, E. T., Boon, M. R., Edelschaap, D., Snaterse, G., Pijl, H., Romijn, J. A., & Rensen, P. C. N. (2015) · Diabetologia · doi:10.1007/s00125-015-3727-0 · Cited by 140 · see citing works
Swanson, L. W. (1998) · Elsevier eBooks · Cited by 139 · see citing works
Induction of neuropeptide Y expression in dorsomedial hypothalamus of diet-induced obese mice
Guan, X.-M., Yu, H., Trumbauer, M. E., Frazier, E. G., der Ploeg, L. H. T. V., & Chen, H. (1998) · Neuroreport · doi:10.1097/00001756-199810260-00015 · Cited by 137 · see citing works
Geerling, J. J., Boon, M. R., Kooijman, S., Parlevliet, E. T., Havekes, L. M., Romijn, J. A., Meurs, I. M., & Rensen, P. C. N. (2014) · Journal of Lipid Research · doi:10.1194/jlr.r045013 · Cited by 137 · see citing works
Burmeister, M. A., Ayala, J. E., Smouse, H., Landivar-Rocha, A., Brown, J. D., Drucker, D. J., Stoffers, D. A., Sandoval, D. A., Seeley, R. J., & Ayala, J. E. (2017) · Diabetes · doi:10.2337/db16-1102 · Cited by 136 · see citing works
Dodd, G. T., Worth, A. A., Nunn, N., Korpal, A. K., Bechtold, D. A., Allison, M. B., Myers, M. G., Statnick, M. A., & Luckman, S. M. (2014) · Cell Metabolism · doi:10.1016/j.cmet.2014.07.022 · Cited by 127 · see citing works
Hsu, T. M., Noble, E. E., Liu, C. M., Cortella, A. M., Konanur, V., Suarez, A. N., Reiner, D. J., Hahn, J. D., Hayes, M. R., & Kanoski, S. E. (2017) · Molecular Psychiatry · doi:10.1038/mp.2017.91 · Cited by 123 · see citing works
Self-citationMietlicki‐Baase, E. G., Ortinski, P. I., Reiner, D. J., Sinon, C. G., McCutcheon, J. E., Pierce, R. C., Roitman, M. F., & Hayes, M. R. (2014) · Journal of Neuroscience · doi:10.1523/jneurosci.0115-14.2014 · Cited by 122 · see citing works
Self-citationThe effect of glucagon-like peptide-1 on energy expenditure and substrate metabolism in humans
Flint, A., Raben, A., Jf, R., Holst, J. J., & Astrup, A. V. (2000) · International Journal of Obesity · doi:10.1038/sj.ijo.0801126 · Cited by 120 · see citing works
Glucagon‐like peptide‐1 in the rat brain: Distribution of expression and functional implication
Gu, G., Roland, B. L., Tomaselli, K. J., Dolman, C. S., Lowe, C., & Heilig, J. S. (2012) · The Journal of Comparative Neurology · doi:10.1002/cne.23282 · Cited by 119 · see citing works
Watts, A. G., Sanchez-Watts, G., & Kelly, A. B. (1999) · The Journal of Neuroscience · doi:10.1523/jneurosci.19-14-06111.1999 · Cited by 102 · see citing works
Self-citationAlhadeff, A. L., Mergler, B. D., Zimmer, D. J., Turner, C. A., Reiner, D. J., Schmidt, H. D., Grill, H. J., & Hayes, M. R. (2017) · Neuropsychopharmacology · doi:10.1038/npp.2016.246 · Cited by 102 · see citing works
Self-citationPPG neurons of the lower brain stem and their role in brain GLP-1 receptor activation
Trapp, S., & Cork, S. C. (2015) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00333.2015 · Cited by 100 · see citing works
Dorsomedial hypothalamic NPY and energy balance control
Bi, S., Kim, Y. J., & Zheng, F. (2012) · Neuropeptides · doi:10.1016/j.npep.2012.09.002 · Cited by 96 · see citing works
The gut hormone glucagon-like peptide-1 produced in brain: is this physiologically relevant?
Trapp, S., & Richards, J. E. (2013) · Current Opinion in Pharmacology · doi:10.1016/j.coph.2013.09.006 · Cited by 93 · see citing works
Li, C., Chen, P., & Smith, M. S. (1998) · Regulatory Peptides · doi:10.1016/s0167-0115(98)00057-3 · Cited by 89 · see citing works
Osaka, T., Endo, M., Yamakawa, M., & Inoue, S. (2005) · Peptides · doi:10.1016/j.peptides.2005.02.016 · Cited by 84 · see citing works
Nucleus accumbens GLP-1 receptors influence meal size and palatability
Dossat, A. M., Diaz, R., Gallo, L. K., Panagos, A., Kay, K. E., & Williams, D. L. (2013) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00137.2013 · Cited by 81 · see citing works
Williams, D. L., Hyvarinen, N., Lilly, N., Kay, K. E., Dossat, A. M., Parise, E. M., & Torregrossa, A. (2011) · Physiology & Behavior · doi:10.1016/j.physbeh.2011.04.005 · Cited by 78 · see citing works
Modulation of Glucagon Receptor Pharmacology by Receptor Activity-modifying Protein-2 (RAMP2)
Weston, C. A., Lu, J. N., Li, N., Barkan, K., Richards, G. O., Roberts, D. J., Skerry, T. M., Poyner, D. R., Pardamwar, M., Reynolds, C. A., et al. (2015) · Journal of Biological Chemistry · doi:10.1074/jbc.m114.624601 · Cited by 77 · see citing works
Lee, S. J., Verma, S., Simonds, S. E., Kirigiti, M. A., Kievit, P., Lindsley, S. R., Loche, A., Smith, M. S., Cowley, M. A., & Grove, K. L. (2013) · Journal of Neuroscience · doi:10.1523/jneurosci.0837-13.2013 · Cited by 74 · see citing works
Self-citationGrove, K. L., Brogan, R. S., & Smith, M. S. (2001) · Endocrinology · doi:10.1210/endo.142.11.8498 · Cited by 65 · see citing works
Effects of glucagon‐like peptide 1 (7–36 amide) on whole‐body protein metabolism in healthy man
Shalev, A., Holst, J. J., & Keller, U. B. (1997) · European Journal of Clinical Investigation · doi:10.1046/j.1365-2362.1997.540613.x · Cited by 62 · see citing works
Hwa, J. J., Ghibaudi, L., Williams, P., Witten, M. B., Tedesco, R., & Strader, C. D. (1998) · Peptides · doi:10.1016/s0196-9781(98)00033-3 · Cited by 59 · see citing works
Cholinergic neurons in the dorsomedial hypothalamus regulate mouse brown adipose tissue metabolism
Jeong, J. H., Lee, D., Blouet, C., Ruiz, H. H., Buettner, C., Chua, S. C., Schwartz, G. J., & Jo, Y. (2015) · Molecular Metabolism · doi:10.1016/j.molmet.2015.03.006 · Cited by 56 · see citing works
Investigating G protein signalling bias at the glucagon‐like peptide‐1 receptor in yeast
Weston, C. J., Poyner, D. R., Patel, V. C., Dowell, S. J., & Ladds, G. (2014) · British Journal of Pharmacology · doi:10.1111/bph.12716 · Cited by 54 · see citing works
Decreased Hypothalamic Glucagon-Like Peptide-1 Receptor Expression in Type 2 Diabetes Patients
ten Kulve, J. S., van Bloemendaal, L., Balesar, R., IJzerman, R. G., Swaab, D. F., Diamant, M., la Fleur, S. E., & Alkemade, A. (2016) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2015-3291 · Cited by 54 · see citing works
Watts, A. G., & Sanchez‐Watts, G. (1995) · The Journal of Comparative Neurology · doi:10.1002/cne.903520403 · Cited by 53 · see citing works
Self-citationLee, S. J., Kirigiti, M. A., Lindsley, S. R., Loche, A., Madden, C. J., Morrison, S. F., Smith, M. S., & Grove, K. L. (2012) · The Journal of Comparative Neurology · doi:10.1002/cne.23265 · Cited by 53 · see citing works
Self-citationYang, Y., Moghadam, A. A., Cordner, Z. A., Liang, N., & Moran, T. H. (2014) · Endocrinology · doi:10.1210/en.2014-1052 · Cited by 46 · see citing works
Heppner, K. M., Marks, S., Holland, J., Ottaway, N., Smiley, D., DiMarchi, R. D., & Pérez–Tilve, D. (2015) · Diabetologia · doi:10.1007/s00125-015-3651-3 · Cited by 44 · see citing works
GLP-1 as a target for therapeutic intervention
Rajeev, S. P., & Wilding, J. P. H. (2016) · Current Opinion in Pharmacology · doi:10.1016/j.coph.2016.08.005 · Cited by 43 · see citing works
Schober, G., Arnold, M., Birtles, S., Buckett, L. K., Pacheco‐López, G., Turnbull, A. V., Langhans, W., & Mansouri, A. (2013) · Journal of Lipid Research · doi:10.1194/jlr.m035154 · Cited by 41 · see citing works
Self-citationRenner, É., Puškaš, N., Dobolyi, Á., & Palkovits, M. (2012) · Peptides · doi:10.1016/j.peptides.2012.02.018 · Cited by 40 · see citing works
Defective adaptive thermogenesis contributes to metabolic syndrome and liver steatosis in obese mice
Poekes, L., Legry, V., Schakman, O., Detrembleur, C., Bol, A., Horsmans, Y., Farrell, G. C., & Leclercq, I. A. (2016) · Clinical Science · doi:10.1042/cs20160469 · Cited by 39 · see citing works
Watts, A. G., & Sanchez‐Watts, G. (2007) · The Journal of Comparative Neurology · doi:10.1002/cne.21316 · Cited by 37 · see citing works
Self-citationHillebrand, J. J., Langhans, W., & Geary, N. (2009) · Obesity · doi:10.1038/oby.2009.341 · Cited by 34 · see citing works
Self-citationZheng, F., Kim, Y. J., Chao, P.-T., & Bi, S. (2013) · Obesity · doi:10.1002/oby.20467 · Cited by 33 · see citing works
Draper, S. J., Kirigiti, M. A., Glavas, M. M., Grayson, B. E., Chong, C. N. A., Jiang, B. S., Smith, M. S., Zeltser, L. M., & Grove, K. L. (2010) · Brain Research · doi:10.1016/j.brainres.2010.03.082 · Cited by 33 · see citing works
Hepatic and intestinal handling of metabolites during feeding in rats
Langhans, W. (1991) · Physiology & Behavior · doi:10.1016/0031-9384(91)90352-o · Cited by 28 · see citing works
Self-citationKim, Y. J., & Bi, S. (2015) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00174.2015 · Cited by 28 · see citing works
Wei, Q., Li, L., Chen, J., Wang, S., & Sun, Z. (2015) · PubMed · Cited by 23 · see citing works
Limiting glucocorticoid secretion increases the anorexigenic property of Exendin-4
Lee, S. J., Diener, K., Kaufman, S., Krieger, J.-P., Pettersen, K. G., Jejelava, N., Arnold, M., Watts, A. G., & Langhans, W. (2016) · Molecular Metabolism · doi:10.1016/j.molmet.2016.04.008 · Cited by 20 · see citing works
Self-citationLi, L., Serre, C. B. D. L., Zhang, N., Yang, L., Li, H., & Bi, S. (2016) · Endocrinology · doi:10.1210/en.2016-1662 · Cited by 16 · see citing works
A Potential Link between Dorsomedial Hypothalamic Nucleus NPY and Energy Balance
Bartness, T. J. (2011) · Cell Metabolism · doi:10.1016/j.cmet.2011.04.006 · Cited by 3 · see citing works
Merchenthaler (1999) · doi:10.1002/(sici)1096-9861(19990111)403:2
Elmquist (1998) · doi:10.1002/(sici)1096-9861(19980615)395:4
Flagged first, then by citations
2 of the 104 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
Glucagon-like peptide 1 (GLP-1)
Müller, T. D., Finan, B., Bloom, S. R., D'Alessio, D., Drucker, D. J., Flatt, P. R., Fritsche, A., Gribble, F., Grill, H. J., Habener, J. F., et al. (2019) · Molecular Metabolism · doi:10.1016/j.molmet.2019.09.010 · Cited by 1,868 · see citing works
“In keeping with this, site-specific disruption of GLP-1R on neurons of the DMH of rats results in significant body weight gain paralleled by a reduction in energy expenditure and BAT heat production [777].”
BackgroundSelf-citationGLP-1 physiology informs the pharmacotherapy of obesity
Drucker, D. J. (2022) · Molecular Metabolism · doi:10.1016/j.molmet.2021.101351 · Cited by 510 · see citing works
“Conversely, selective knockdown of the GLP1R in the dorsomedial nucleus of the rat hypothalamus reduced adipose tissue uncoupling protein 1 (UCP1) expression, decreased BAT temperature and energy expenditure, and increased body weight and adiposity [4].”
BackgroundSignaling pathways in obesity: mechanisms and therapeutic interventions
Wen, X.-Q., Zhang, B.-H., Wu, B., Xiao, H.-T., Li, Z.-H., Li, R.-Y., Xu, X.-W., & Li, T. (2022) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-022-01149-x · Cited by 376 · see citing works
“Central signaling may play a role in GLP-1-induced thermogenesis since GLP-1 administered into the dorsomedial hypothalamus of rats increases BAT thermogenesis and triglyceride mobilization in the liver, whereas loss of GLP-1 signaling in the dorsomedial hypothalamus area reduces BAT thermogenesis and increases adipos…”
ResultRevisiting the Complexity of GLP-1 Action from Sites of Synthesis to Receptor Activation
McLean, B. A., Wong, C. K., Campbell, J. E., Hodson, D. J., Trapp, S., & Drucker, D. J. (2021) · Endocrine Reviews · doi:10.1210/endrev/bnaa032 · Cited by 289 · see citing works
Treatment of type 2 diabetes: challenges, hopes, and anticipated successes
Nauck, M. A., Wefers, J., & Meier, J. J. (2021) · The Lancet Diabetes & Endocrinology · doi:10.1016/s2213-8587(21)00113-3 · Cited by 300 · see citing works
Holt, M. K., Richards, J. E., Cook, D. R., Brierley, D. I., Williams, D. L., Reimann, F., Gribble, F. M., & Trapp, S. (2019) · Diabetes · doi:10.2337/db18-0729 · Cited by 212 · 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
“Similarly, administration of the incretin hormone GLP-1 in the DMH increases BAT thermogenesis [82].”
The physiological control of eating: signals, neurons, and networks
Watts, A. G., Kanoski, S. E., Sanchez-Watts, G., & Langhans, W. (2022) · Physiological Reviews · doi:10.1152/physrev.00028.2020 · Cited by 168 · see citing works
Self-citationTrapp, S., & Brierley, D. I. (2022) · British Journal of Pharmacology · doi:10.1111/bph.15638 · Cited by 154 · see citing works
“diture, to cardiovascular effects and neuroprotective actions (Barragan et al., 1999; During et al., 2003; Kanoski et al., 2016; Lee et al., 2018; Tang-Christensen et al., 1996; Turton et al., 1996).”
BackgroundGLP-1 increases preingestive satiation via hypothalamic circuits in mice and humans
Kim, K. S., Park, J. S., Hwang, E., Park, M. J., Shin, H. Y., Lee, Y. H., Kim, K. M., Gautron, L., Godschall, E., Portillo, B., et al. (2024) · Science · doi:10.1126/science.adj2537 · Cited by 148 · see citing works
Neuropeptide Y Is an Immunomodulatory Factor: Direct and Indirect
Chen, W.-C., Liu, Y., Liu, W.-F., Zhou, Y., He, H., & Lin, S. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.580378 · Cited by 136 · see citing works
“Overexpression of NPY in DMH decreased the expression of UCP1 in BAT, leading to insulin resistance (122); however, the downregulation of DMH NPY improved glucose homeostasis and enhanced insulin sensitivity (103).”
BackgroundHe, Z., Gao, Y., Lieu, L., Afrin, S., Cao, J., Michael, N. J., Dong, Y., Sun, J., Guo, H., & Williams, K. W. (2019) · Molecular Metabolism · doi:10.1016/j.molmet.2019.07.008 · Cited by 128 · see citing works
“These observations are consistent with previous reports showing liraglutide fails to bind directly to NPY neurons due to low or absent GLP-1 receptor expression [31,72].”
ResultTargeting the GIPR for obesity: To agonize or antagonize? Potential mechanisms
Campbell, J. E. (2021) · Molecular Metabolism · doi:10.1016/j.molmet.2020.101139 · Cited by 133 · see citing works
“Although Ap2-Cre has documented activity in brown adipocytes [41], it is interesting to note that the rescue model of GIPR failed to increase GIPR expression in BAT [51].”
BackgroundInfluentialGlucagon-Like Peptide-1: New Regulator in Lipid Metabolism
Bu, T., Sun, Z., Pan, Y., Deng, X., & Yuan, G. (2024) · Diabetes & Metabolism Journal · doi:10.4093/dmj.2023.0277 · Cited by 131 · see citing works
Kabahizi, A., Wallace, B., Lieu, L., Chau, D., Dong, Y., Hwang, E., & Williams, K. W. (2022) · British Journal of Pharmacology · doi:10.1111/bph.15682 · Cited by 126 · see citing works
“…selective expression of GLP-1 receptor in the dorsomedial hypothalamus appears analogous to the GLP-1 receptor-dependent regulation of arcuate NPY neurons, as GLP-1 receptor expression on GABAergic neurons negatively regulates NPY expression within the dorsomedial hypothalamus (Lee et al., 2018).”
BackgroundInfluentialVarin, E. M., Mulvihill, E. E., Baggio, L. L., Koehler, J. A., Cao, X., Seeley, R. J., & Drucker, D. J. (2019) · Cell Reports · doi:10.1016/j.celrep.2019.05.055 · Cited by 104 · see citing works
“, 2017), and selective reduction of GLP-1R activitywithin different regions of the rat brain impaired the control of either food intake, meal size, body weight, energy expenditure, or adiposity (Alhadeff et al., 2017; Lee et al., 2018; López-Ferreras et al., 2018).”
BackgroundSingh, I., Wang, L., Xia, B., Liu, J., Tahiri, A., El Ouaamari, A., Wheeler, M. B., & Pang, Z. P. (2022) · Cell & Bioscience · doi:10.1186/s13578-022-00914-3 · Cited by 98 · see citing works
“Consistent with this notion, knockdown of GLP-1R in the dorsomedial hypothalamus increased food intake, decreased energy expenditure, and increased body weight over weeks of observation [16].”
BackgroundA novel mouse model of glucagon‐like peptide‐1 receptor expression: A look at the brain
Graham, D. L., Durai, H. H., Trammell, T. S., Noble, B. L., Mortlock, D. P., Galli, A., & Stanwood, G. D. (2020) · The Journal of Comparative Neurology · doi:10.1002/cne.24905 · Cited by 89 · see citing works
Switching on the furnace: Regulation of heat production in brown adipose tissue
Li, L., Li, B., Li, M., & Speakman, J. R. (2019) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2019.07.005 · Cited by 85 · see citing works
Glucagon-Like Peptide-1 (GLP-1) in the Integration of Neural and Endocrine Responses to Stress
Diz-Chaves, Y., Herrera-Pérez, S., González-Matías, L. C., Lamas, J. A., & Mallo, F. (2020) · Nutrients · doi:10.3390/nu12113304 · Cited by 84 · see citing works
“GLP-1 emerges as a crucial modulator of BAT thermogenesis in mice by increasing SNS activity without altering peripheral insulin responsiveness [162].”
BackgroundHypothalamic AMPK as a Mediator of Hormonal Regulation of Energy Balance
Wang, B., & Cheng, K. K. Y. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19113552 · Cited by 84 · see citing works
“Although injection of liraglutide in DMH has no effect on BAT thermogenesis, injection of native GLP-1 in DMH increases the core body temperature and thermogenic program in BAT [138,167].”
BackgroundThe Role of AMPK Signaling in Brown Adipose Tissue Activation
van der Vaart, J. I., Boon, M. R., & Houtkooper, R. H. (2021) · Cells · doi:10.3390/cells10051122 · Cited by 82 · see citing works
“In rats, injection of GLP‐1 in the DMH increases core body temperature and expression of thermogenic markers [92].”
BackgroundMishra, D., Richard, J. E., Marić, I., Porteiro, B., Häring, M., Kooijman, S., Musovic, S., Eerola, K., López‐Ferreras, L., Peris, E., et al. (2019) · Cell Reports · doi:10.1016/j.celrep.2019.02.044 · Cited by 80 · see citing works
Huang, Z., Liu, L., Zhang, J., Conde, K., Phansalkar, J., Li, Z., Yao, L., Xu, Z., Wang, W., Zhou, J., et al. (2022) · Science Advances · doi:10.1126/sciadv.abn5345 · Cited by 78 · see citing works
“7A), although RPa, which mediates a sympathetic activity (41, 48), also receives some afferents from DMHGLP-1R (fig.”
BackgroundIncretin Hormones in Obesity and Related Cardiometabolic Disorders: The Clinical Perspective
Michałowska, J. M., Miller‐Kasprzak, E., & Bogdański, P. (2021) · Nutrients · doi:10.3390/nu13020351 · Cited by 69 · see citing works
“revealed that central injection of liraglutide stimulates BAT thermogenesis and adipocyte browning through hypothalamic AMP-activated protein kinase (AMPK) [80], and the direct administration of GLP-1 into the dorsomedial hypothalamus (DMH) increases BAT thermogenesis through DMH GLP-1R signaling [83].”
BackgroundSaglietto, A., Falasconi, G., Penela, D., Francia, P., Sau, A., Ng, F. S., Dusi, V., Castagno, D., Gaïta, F., Berruezo, A., et al. (2024) · European Journal of Clinical Investigation · doi:10.1111/eci.14292 · Cited by 64 · see citing works
“34,35 This peculiarity might explain why semaglutide, T A B L E 1 D e t a i l s o f t h e s t u d i e s i n c l u d e d i n t h e p r e s e n t s y s t e m a t i c r e v i e w a n d m e t a - a n a l y s i s .”
Zhang, F., Chen, Z., Wu, D., Tian, L., Chen, Q., Ye, Y., Chen, W., Wu, X., Wu, P., Yuan, W., et al. (2021) · iScience · doi:10.1016/j.isci.2021.103382 · Cited by 54 · see citing works
Holt, M. K., & Rinaman, L. (2021) · British Journal of Pharmacology · doi:10.1111/bph.15576 · Cited by 44 · see citing works
Le, T. D. V., Fathi, P. A., Watters, A. B., Ellis, B. J., Besing, G.-L. K., Bozadjieva-Kramer, N., Perez, M. B., Sullivan, A. I., Rose, J. P., Baggio, L. L., et al. (2023) · Molecular Metabolism · doi:10.1016/j.molmet.2023.101718 · Cited by 48 · see citing works
Obesity pharmacotherapy: incretin action in the central nervous system
Boer, G. A., Hay, D. L., & Tups, A. (2022) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2022.11.001 · Cited by 43 · see citing works
Park, J. S., Kim, K. S., & Choi, H. J. (2025) · Diabetes & Metabolism Journal · doi:10.4093/dmj.2025.0106 · Cited by 48 · see citing works
“GLP-1R are known to be expressed in the neurons of the DMH of mice and humans, and previous studies have emphasized its role in regulating metabolic responses by exendin-4 [68,69].”
Zheng, H., Reiner, D. J., Hayes, M. R., & Rinaman, L. (2019) · Journal of Neuroscience · doi:10.1523/jneurosci.2180-18.2019 · Cited by 41 · see citing works
“used to reduce translatable GLP1R mRNA in different brain regions (Schmidt et al., 2016; Alhadeff et al., 2017; Tuesta et al., 2017; Lee et al., 2018; López-Ferreras et al., 2018).”
MethodResultSelf-citationNovel GLP-1-based Medications for Type 2 Diabetes and Obesity
Son, J. W., le Roux, C. W., Blüher, M., Nauck, M. A., & Lim, S. (2026) · Endocrine Reviews · doi:10.1210/endrev/bnaf036 · Cited by 33 · see citing works
Exercise-induced hypothalamic neuroplasticity: Implications for energy and glucose metabolism
Hwang, E., Portillo, B., Grose, K. C., Fujikawa, T., & Williams, K. W. (2023) · Molecular Metabolism · doi:10.1016/j.molmet.2023.101745 · Cited by 34 · see citing works
“[83] Lee SJ, Sanchez-Watts G, Krieger JP, Pignalosa A, Norell PN, Cortella A, et al.”
BackgroundGLP-1 receptor agonists and myocardial metabolism in atrial fibrillation
Zhong, J., Chen, H., Liu, Q., Zhou, S., Liu, Z., & Xiao, Y. (2023) · Journal of Pharmaceutical Analysis · doi:10.1016/j.jpha.2023.12.007 · Cited by 30 · see citing works
“Second, GLP-1 RAs act on GLP-1 R-enriched areas in the dorsome-dial hypothalamus to modulate sympathetic nerve activity, which is important for body weight regulation and brown adipose tissue thermogenesis, thereby reducing body weight [98].”
BackgroundEffect of central JAZF1 on glucose production is regulated by the PI3K‐Akt‐AMPK pathway
Zhou, M., Xu, X., Wang, H., Yang, G., Yang, M., Zhao, X., Guo, H., Song, J., Zheng, H., Zhu, Z., et al. (2020) · The FASEB Journal · doi:10.1096/fj.201901836rr · Cited by 30 · see citing works
GLP-1 mimetics as a potential therapy for nonalcoholic steatohepatitis
Chen, Y., Xu, Y.-N., Ye, C.-Y., Feng, W., Zhou, Q., Yang, D., & Wang, M. (2021) · Acta Pharmacologica Sinica · doi:10.1038/s41401-021-00836-9 · Cited by 32 · see citing works
“DNL of the liver is most commonly produced by carbohydrate catabolism.”
BackgroundInfluentialUpdated Role of Neuropeptide Y in Nicotine-Induced Endothelial Dysfunction and Atherosclerosis
Zheng, Y.-L., Wang, W.-D., Li, M., Lin, S., & Lin, H. (2021) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2021.630968 · Cited by 27 · see citing works
Hou, L., Du, J.-Y., Dong, Y., Wang, M., Wang, L., & Zhao, J. (2024) · Human Cell · doi:10.1007/s13577-024-01038-1 · Cited by 28 · see citing works
Brown Adipose Tissue: A Metabolic Regulator in a Hypothalamic Cross Talk?
Henningsen, J. B., & Schéele, C. (2020) · Annual Review of Physiology · doi:10.1146/annurev-physiol-032420-042950 · Cited by 24 · see citing works
Long-term functional alterations following prenatal GLP-1R activation
Graham, D. L., Madkour, H. S., Noble, B. L., Schatschneider, C. W., & Stanwood, G. D. (2021) · Neurotoxicology and Teratology · doi:10.1016/j.ntt.2021.106984 · Cited by 23 · see citing works
Li, C., Xu, Y., Hu, Y., Zhou, X., Huang, Z., Ye, J., & Rao, Y. (2022) · Pharmacological Research · doi:10.1016/j.phrs.2022.106136 · Cited by 24 · see citing works
GLP-1 physiology and pharmacology along the gut-brain axis
Beutler, L. R. (2026) · Journal of Clinical Investigation · doi:10.1172/jci194744 · Cited by 28 · see citing works
“Additional studies confirmed that virus-mediated GLP-1R knockdown in rats and mice increased bodyweight, but found this occurred through decreased energy expenditure, not increased food intake (111, 112).”
Food phenolics stimulate adipocyte browning via regulating gut microecology
Wang, Z., Zeng, M., Wang, Z., Qin, F., Wang, Y., Chen, J., Christian, M., & He, Z. (2021) · Critical Reviews in Food Science and Nutrition · doi:10.1080/10408398.2021.1997905 · Cited by 22 · see citing works
Glucagon-like peptide (GLP)-1 regulation of lipid and lipoprotein metabolism
HOFFMAN, S. S., & Adeli, K. (2024) · Medical Review · doi:10.1515/mr-2024-0011 · Cited by 22 · see citing works
“Interestingly, this e ff ect on WAT was seen to be blunted in a diet-induced obese mouse model [96].”
BackgroundMaejima, Y., Yokota, S., Shimizu, M., Horita, S., Kobayashi, D., Hazama, A., & Shimomura, K. (2021) · Nutrition & Metabolism · doi:10.1186/s12986-021-00582-z · Cited by 21 · see citing works
“It is reported that 16% of GLP-1R expressing neurons are glutamatergic neurons [19].”
BackgroundResultInfluentialSingh, A., Zapata, R. C., Pezeshki, A., Workentine, M. L., & Chelikani, P. K. (2019) · The FASEB Journal · doi:10.1096/fj.201801627rrr · Cited by 21 · see citing works
Pharmacological modulation of adaptive thermogenesis: new clues for obesity management?
Genchi, V. A., Palma, G., Sorice, G. P., D’Oria, R., Caccioppoli, C., Marrano, N., Biondi, G., Caruso, I., Cignarelli, A., Natalicchio, A., et al. (2023) · Journal of Endocrinological Investigation · doi:10.1007/s40618-023-02125-0 · Cited by 19 · see citing works
“Consistent with these findings, selective in vivo ablation of GLP-1R in the neuronal circuits of both DMH and VMH nuclei blunted the effect of liraglutide on body weight, in addition to reducing the thermogenic and browning action mediated by liraglutide and exendin-4 [30, 148, 154]; these observations suggest that en…”
BackgroundALVARES, D. C. L., HOFFMAN, S. S., Stankovic, B., & Adeli, K. (2018) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2018.12.010 · Cited by 19 · see citing works
Key role for hypothalamic interleukin-6 in food-motivated behavior and body weight regulation
López‐Ferreras, L., Longo, F., Richard, J. E., Eerola, K., Shevchouk, O. T., Tuzinovic, M., & Skibicka, K. P. (2021) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2021.105284 · Cited by 18 · see citing works
“A FLIR T500-Series thermal camera was used to measure the temperature of the area above the brown adipose tissue (BAT; interscapular depot) and core temperature (ear), as previously described (Lee et al., 2018; Martinez-Sanchez et al., 2017; Matesanz et al., 2017).”
Regulatory Roles of GADD45α in Skeletal Muscle and Adipocyte
You, W., Xu, Z., & Shan, T. (2019) · Current Protein and Peptide Science · doi:10.2174/1389203720666190624143503 · Cited by 16 · see citing works
AlZaim, I., Eid, A. H., Abd‐Elrahman, K. S., & EL‐Yazbi, A. F. (2022) · Biochemical Pharmacology · doi:10.1016/j.bcp.2022.115337 · Cited by 16 · see citing works
Brown, J. D., McAnally, D., Ayala, J. E., Burmeister, M. A., Morfa, C. J., Smith, L. H., & Ayala, J. E. (2018) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00459.2017 · Cited by 16 · see citing works
“Furthermore, knockdown of the GLP-1R in the dorsomedial hypothalamus results in decreased BAT activity, increased weight gain, and increased adiposity (38).”
BackgroundRIIβ‐PKA in GABAergic Neurons of Dorsal Median Hypothalamus Governs White Adipose Browning
Wang, B., Zhao, M., Su, Z., Jin, B., Yang, X., Zhang, C., Guo, B., Li, J., Hong, W., Liu, J., et al. (2022) · Advanced Science · doi:10.1002/advs.202205173 · Cited by 14 · see citing works
Poole, E. I., McGavin, J. J., Cochkanoff, N. L., & Crosby, K. M. (2019) · MethodsX · doi:10.1016/j.mex.2019.07.005 · Cited by 15 · see citing works
Zhang, C., Barkholt, P., Nielsen, J. C., Thorbek, D. D., Rigbolt, K. T. G., Vrang, N., Woldbye, D. P. D., & Jelsing, J. (2019) · Brain Research · doi:10.1016/j.brainres.2019.146538 · Cited by 15 · see citing works
Chondronikola, M. (2020) · Current Opinion in Clinical Nutrition & Metabolic Care · doi:10.1097/mco.0000000000000662 · Cited by 14 · see citing works
“In rodents, GLP1 agonism stimulates BAT metabolic activity, increasing glucose and lipid combustion for the thermogenesis [20].”
BackgroundWang, X., Wang, Q., Zhao, M., Xu, Y., Fu, B., Zhang, L., Wu, S., Yang, D., & Jia, C. (2023) · Molecular & Cellular Proteomics · doi:10.1016/j.mcpro.2023.100525 · Cited by 13 · see citing works
Integration of Glucagon-Like Peptide 1 Receptor Actions Through the Central Amygdala
Duran, M., Willis, J. R., Dalvi, N., Fokakis, Z. N., VIRKUS, S., & Hardaway, J. A. (2025) · Endocrinology · doi:10.1210/endocr/bqaf019 · Cited by 13 · see citing works
Hypothalamic CDK4 regulates thermogenesis by modulating sympathetic innervation of adipose tissues
Castillo‐Armengol, J., Barquissau, V., Geller, S., Ji, H., Severi, I., Venema, W., Fernandez, E. A., Moret, C., Huber, K., Leal-Esteban, L. C., et al. (2020) · EMBO Reports · doi:10.15252/embr.201949807 · Cited by 13 · see citing works
“There, several hypothalamic nuclei integrate this sensory information to regulate the thermogenic response (Oldfield et al , 2002; Monda et al , 2005; Morrison et al , 2012; Contreras et al , 2015; Martins et al , 2016; Lee et al , 2018).”
Progress in the contrary effects of glucagon-like peptide-1 and chemerin on obesity development
Zhang, Q., Ye, J., & Wang, X. (2023) · Experimental Biology and Medicine · doi:10.1177/15353702231214270 · Cited by 12 · see citing works
“63 Therefore, GLP-1R signaling in DMH is well placed to regulate energy balance by controlling sympathetic outflow and BAT function.”
BackgroundGLP-1 and Its Role in Glycogen Production: A Narrative Review
Lotosky, J., Jean, X., Altankhuyag, A., Khan, S. R., Bernotas, A., Sharafshah, A., Blum, K., Posner, A. R., & Thanos, P. K. (2025) · Biomedicines · doi:10.3390/biomedicines13071610 · Cited by 13 · see citing works
“A loss of neuronal GLP-1R decreases energy expenditure and uncoupling protein 1 expression (UCP1), where GLP-1 activity is necessary for the dorsomedial hypothalamus to activate brown-adipose-tissue thermogenesis [109].”
Glucagon‐Like Peptide‐1 Links Ingestion, Homeostasis, and the Heart
Krieger, J., Daniels, D., Lee, S. J., Mastitskaya, S., & Langhans, W. (2024) · Comprehensive physiology · doi:10.1002/cph4.7 · Cited by 13 · see citing works
“Recently, some of us showed that GLP-1R activation in the DMH increased BAT temperature in rats and chronic reduction of GLP-1R signaling in the DMH reduced BAT thermogenic capacity and increased fat accumulation in rats on a standard chow diet (Lee et al. 2018).”
Self-citationGlucagon-Like Peptide 1 (GLP-1) Action on Hypothalamic Feeding Circuits
Hwang, E., Portillo, B., & Williams, K. W. (2025) · Endocrinology · doi:10.1210/endocr/bqaf125 · Cited by 10 · see citing works
Hu, H., Lu, X., He, Y., Li, J., Wang, S., Luo, Z., Wang, Y., Wei, J., Huang, H., Duan, C., et al. (2024) · The Journal of Nutritional Biochemistry · doi:10.1016/j.jnutbio.2024.109703 · Cited by 9 · see citing works
Leuthardt, A. S., Boyle, C. N., Raun, K., Lutz, T. A., John, L. M., & Foll, C. L. (2023) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2023.175912 · Cited by 9 · see citing works
GLP-1 and IL-6 regulates obesity in the gut and brain
Yang, K., Wu, Y., He, Y., Dai, J.-X., Luo, Y.-L., Xie, J.-H., & Ding, W. (2024) · Life Sciences · doi:10.1016/j.lfs.2024.123339 · Cited by 8 · see citing works
Hindbrain insulin controls feeding behavior
Eerola, K., Longo, F., Reinbothe, T. M., Richard, J. E., Shevchouk, O. T., López‐Ferreras, L., Mishra, D., Asker, M., Tolö, J., MIRANDA, C. A., et al. (2022) · Molecular Metabolism · doi:10.1016/j.molmet.2022.101614 · Cited by 8 · see citing works
A Brain Reward Circuit Inhibited By Next-Generation Weight Loss DrugsPreprint
Godschall, E., Güngül, T. B., Sajonia, I. R., Buyukaksakal, A. K., Li, O. D.-A., Ogilvie, S., Keeler, A. B., Tian, G., Koita, O., Shi, Y., et al. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.12.12.628169 · Cited by 8 · see citing works
“When targeting the DMH, a BMH subnucleus recently implicated in encoding satiation 26,57,65 , we found similar selective effects on SD intake ( Fig.”
Povysheva, N. V., Zheng, H., & Rinaman, L. (2021) · Neurobiology of Stress · doi:10.1016/j.ynstr.2021.100363 · Cited by 7 · see citing works
Mattar, P., Jaque, C., Teske, J. A., Morselli, E., Kerr, B., Cortés, V., Baudrand, R. F., & Perez‐Leighton, C. E. (2023) · Frontiers in Endocrinology · doi:10.3389/fendo.2023.1164047 · Cited by 7 · see citing works
“The latter result is consistent with data showing that activation of the GLP1R in the dorsal medial hypothalamus (a brain site likely reached by EX4 ICV administration into the third ventricle) can increase BAT thermogenesis (47).”
ResultPhysiology and pharmacology of glucagon-like peptide-1 receptor
Куркин, Д. В., Bakulin, D. A., Morkovin, E. I., Petrov, V. I., Strygin, A. V., Koryanova, K. N., Gorbunova, Y. V., Kolosov, Y. A., Ivanova, O. V., Pavlova, E. V., et al. (2024) · Pharmacy & Pharmacology · doi:10.19163/2307-9266-2023-11-4-347-380 · Cited by 6 · see citing works
Blevins, J. E., Honeycutt, M. K., Slattery, J. D., Goldberg, M., Rambousek, J. R., Tsui, E. W., Dodson, A. D., Shelton, K. A., Salemeh, T. S., Elfers, C., et al. (2024) · Frontiers in Endocrinology · doi:10.3389/fendo.2024.1432928 · Cited by 6 · see citing works
Zhou, M., Du, M., Tang, R., Liu, H., Gao, Z., Wang, Y., You, H., Hao, J.-W., Ji, Z., Wang, D., et al. (2023) · Neuroendocrinology · doi:10.1159/000529438 · Cited by 4 · see citing works
Singh, I., Wang, L., Xia, B., Liu, J., Tahiri, A., Ouaamari, A. E., Wheeler, M. B., & Pang, Z. P. (2022) · Research Square · doi:10.21203/rs.3.rs-1971723/v1 · Cited by 4 · see citing works
Cheng, L., Gan, M., Wang, H., Song, Y., Bai, Y., & Zhang, D. (2026) · Phytotherapy Research · doi:10.1002/ptr.70254 · Cited by 3 · see citing works
Xu, Z., Wen, S., Dong, M., & Zhou, L. (2024) · Diabetes Obesity and Metabolism · doi:10.1111/dom.16146 · Cited by 3 · see citing works
“68 Consequently, it is possible to infer that GLP-1 can induce an increase in BAT thermogenesis by stimulating GLP-1R-expressing neurons in the DMH, presumably through the regulation of sympathetic nerve activity.”
Alves, G. A. M., Teranishi, M., Majumdar, R., Khan, F., Dodeja, M., Ortega, A. C. T. D. C. G., Acerboni, M., Arachchige, A. S. P. M., & James, F. (2026) · Chronic Diseases and Translational Medicine · doi:10.1002/cdt3.70048 · Cited by 2 · see citing works
“Complementary studies show that central GLP‐1R activation increases sympathetic outflow to brown and white adipose tissue, enhancing thermogenesis and fatty acid uptake, although these responses may be blunted in diet‐induced obesity [31].”
Serendipity and spontaneity – Critical components in 40 years of academia
Langhans, W. (2019) · Physiology & Behavior · doi:10.1016/j.physbeh.2019.02.011 · Cited by 2 · see citing works
Self-citationLe, T. D. V., Fathi, P. A., Watters, A. B., Ellis, B. J., Bozadjieva-Kramer, N., Perez, M. B., Sullivan, A. I., Rose, J. P., Baggio, L. L., Koehler, J. A., et al. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.01.03.522509 · Cited by 2 · see citing works
Mechanisms of glucagon-like-peptide 1 in the brain beyond metabolic effects
Kim, K. S., Park, J. S., & Choi, H. J. (2025) · Annals of Pediatric Endocrinology & Metabolism · doi:10.6065/apem.2448320.160 · Cited by 2 · see citing works
“Other studies also highlighted the crucial role of DMH GLP-1R neurons in metabolism [49,62].”
Insights into the mechanisms of body weight control
Pereira, S. (2025) · AJP Advances in Physiology Education · doi:10.1152/advan.00091.2025 · Cited by 1 · see citing works
Recent developments in GPCR signalling in appetite regulation
Brittain, H. R., & Gorvin, C. M. (2026) · Bioscience Reports · doi:10.1042/bsr20250120 · Cited by 1 · see citing works
“GLP-1R at the DMH regulates energy expenditure and feeding [65] and at the PVN suppresses feeding [66].”
The central amygdala gates exogenous glucagon-like peptide 1 signals
Duran, M., Zeng, N., Cutts, E. J., POLAMARASETTY, A., Rodríguez, M., Habegger, K. M., & Hardaway, J. A. (2026) · Molecular Metabolism · doi:10.1016/j.molmet.2026.102403 · Cited by 1 · see citing works
“Within the dorsomedial hypothalamus, viral knockdown of GLP-1R expressing neurons fails to produce hyperphagia but decreases energy expenditure and attenuates Ex-4 induced hypophagia [36].”
Sanetra, A. M., Palus‐Chramiec, K., Chrobok, Ł., Jeczmien‐Lazur, J. S., Klich, J. D., & Lewandowski, M. H. (2023) · Molecular and Cellular Neuroscience · doi:10.1016/j.mcn.2023.103873 · Cited by 1 · see citing works
“In line with previous reports (Merchenthaler et al., 1999; Tang-Christensen et al., 2000, 2001; Cork et al., 2015; Lee et al., 2018; Maejima et al., 2021; Huang et al., 2022), we observed fluorescent signal from both Glp1r-and Glp2r -targeting probes within the DMH.”
BackgroundResultInfluentialFischer, S. V., Siqueira, B. S., Cancian, C. R. C., Montes, E. G., Nogaroto, V., Svidnicki, P. V., & Grassiolli, S. (2024) · Einstein (São Paulo) · doi:10.31744/einstein_journal/2024ao0619 · Cited by 1 · see citing works
How blockbuster obesity drugs create a full feeling — even before one bite of food
Lenharo, M. (2024) · Nature · doi:10.1038/d41586-024-02106-0 · Cited by 1 · see citing works
Glucagon‐Like Peptide‐1 Receptor Activators
Wagner, M., Evers, A., Bossart, M., & Konkar, A. A. (2021) · Burger's Medicinal Chemistry and Drug Discovery · doi:10.1002/0471266949.bmc268
GLP-1RA Promotes Beige Differentiation in Adipose Tissue
刘, 臻. (2024) · Advances in Clinical Medicine · doi:10.12677/acm.2024.143795
Maintaining Fat-Free Mass and Muscle Mass during obesity therapy with Incretin-Mimetic Drugs
Popiela, D., Urbańska, K., Stojak, Ł., Grego, M., Kwiatkowski, F., Baczewski, M., Grego, K., & Czyż, W. (2025) · Quality in Sport · doi:10.12775/qs.2025.37.57000
Bueter, M., Alceste, D., Jucker, N., van der Burgh, Y., File, B., Thalheimer, A., Steinert, R. E., Spector, A. C., Maurer, S., Hazebroek, E. J., et al. (2025) · Research Square · doi:10.21203/rs.3.rs-6018162/v1
Maejima, Y., Yokota, S., Shimizu, M., Horita, S., Kobayashi, D., Hazama, A., & Shimomura, K. (2021) · Figshare · doi:10.6084/m9.figshare.14746675
The central amygdala integrates exogenous glucagon-like peptide 1 signalsPreprint
Duran, M., Zeng, N., Cutts, E. J., Habegger, K. M., & Hardaway, J. A. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.04.06.716705
“…[8], [9], [10], [11], [12], [13], [14], [15], [16], [17], [18], [19], [20], [21], [22], [23], [24], [25], [26], [27], [28], [29], [30], [31], [32], [33], [34], [35], [36], [37], [38], [39], [40], [41], [42], [43], [44], [45], [46], [47], [48], [49], [50], [51], [52], [53], [54], [55], [56], [57].”
Liu, H., 张庆红, Du, M., Hao, J., 牛玉梅, You, H., Cao, D., Tang, R., 杨艳艳, Wei, X., et al. (2026) · Clinical Nutrition · doi:10.1016/j.clnu.2026.106740
Burmeister, M. A., Brown, S. A., Greer, J. J., Hoggatt, T. J., & Zumwalt, W. (2026) · Frontiers in Endocrinology · doi:10.3389/fendo.2026.1925534
“These paradoxical events occur because activation of hypothalamic GLP-1R promotes non-shivering IBAT thermogenesis via increased sympathetic out fl ow; reduced FI and BW, in turn, lower CT to conserve energy (55, 56).”
- Authors
- Lee, S. J., Sanchez-Watts, G., Krieger, J.-P., Pignalosa, A., Norell, P. N., Cortella, A., Pettersen, K. G., Vrdoljak, D., Hayes, M. R., Kanoski, S. E., Langhans, W., & Watts, A. G.
- Affiliations
- ETH Zurich (CH)
- University of Southern California (US)
- University of Pennsylvania (US)
- Corresponding author
- Lee, Shin J.
- ORCID
- Venue
- Molecular Metabolism
- Publisher
- Elsevier BV
- Published
- 2018-05
- Volume
- 11
- Pages
- 33-46
- ISSN
- 2212-8778 (ISSN-L)
- PMC
- PMC6001878
- OpenAlex
- W2789458740
- Cited by
- 95
- References
- 104
- Citations by year
- 2026: 8 · 2025: 9 · 2024: 15 · 2023: 11 · 2022: 9 · 2021: 18 · 2020: 9 · 2019: 12 · 2018: 4
- FWCI
- 6.05
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Molecular Metabolism (publishedVersion, cc-by-nc-nd)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Repository for Publications and Research Data (ETH Zurich) (submittedVersion, cc-by-nc-nd)
- ETH Zürich Research Collection
- Funders
- Eidgenössische Technische Hochschule Zürich (NS029728, IZK0Z3 173687, DK104897, 47 12-2, IZK0Z3 158027, NIH-DK096139)
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (PMPDP3_151360)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Keywords
- glucagon-like peptide-1, dorsomedial hypothalamus, GLP-1 receptor, brown adipose tissue thermogenesis, adiposity, energy expenditure, UCP1, hepatic steatosis, de novo lipogenesis, insulin resistance, neuropeptide Y neurons, GABAergic neurons, exendin-4, energy balance, body weight regulation
- MeSH terms
- Glucagon-Like Peptide-1 Receptor, Uncoupling Protein 1, Exenatide, Animals, Adipose Tissue, Brown, Hypothalamus, Insulin Resistance, Male, Neuropeptide Y, Signal Transduction, Rats, Sprague-Dawley, Thermogenesis, Adiposity, Lipogenesis, Rats, Glucagon-Like Peptide 1, GABAergic Neurons
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
