microRNA-33 controls hunger signaling in hypothalamic AgRP neurons
Open accessAbstract
AgRP neurons drive hunger, and excessive nutrient intake is the primary driver of obesity and associated metabolic disorders. While many factors impacting central regulation of feeding behavior have been established, the role of microRNAs in this process is poorly understood. Utilizing unique mouse models, we demonstrate that miR-33 plays a critical role in the regulation of AgRP neurons, and that loss of miR-33 leads to increased feeding, obesity, and metabolic dysfunction in mice. These effects include the regulation of multiple miR-33 target genes involved in mitochondrial biogenesis and fatty acid metabolism. Our findings elucidate a key regulatory pathway regulated by a non-coding RNA that impacts hunger by controlling multiple bioenergetic processes associated with the activation of AgRP neurons, providing alternative therapeutic approaches to modulate feeding behavior and associated metabolic diseases.
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miR-33a controls hunger signaling in hypothalamic AgRP neurons possibly through several miR-33 target genes such as PRKAA1, Ppargc1a, CPT1a and CROT; thus, loss of miR-33a leads to increased feeding, obesity, and metabolic dysfunction in mice.
“MiR-33a has been shown to control hunger signaling in hypothalamic AgRP neurons possibly through several miR-33 target genes such as PRKAA1, Ppargc1a, CPT1a and CROT; thus, loss of miR-33a leads to increased feeding, obesity, and metabolic dysfunction in mice 41) .”
From Critical Role of microRNA-33a/b in Cardiovascular and Metabolic Disease: Molecular Mechanisms and Therapeutic Perspectives (2026) · cites this paper as [41]
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Cites
Watterson, K. R., Bestow, D., Gallagher, J. R., Hamilton, D. L., Ashford, F. B., Meakin, P. J., & Ashford, M. L. J. (2012) · Neurosignals · doi:10.1159/000334144 · Cited by 3,395 · see citing works
AMP-kinase regulates food intake by responding to hormonal and nutrient signals in the hypothalamus
Minokoshi, Y., Alquier, T., Furukawa, N., Kim, Y.-B., Lee, A., Xue, B., Mu, J., Foufelle, F., Ferré, P., Birnbaum, M. J., et al. (2004) · Nature · doi:10.1038/nature02440 · Cited by 1,637 · cited 1× · see citing works
“…be important for the ability of thehypothalamustoproperlyregulatefeedingbehaviorinresponseto changes in nutrient status, and inhibition of hypothalamic AMPK impairs the regulation of feeding behavior in response to fasting and refeeding or stimulation with hormones like ghrelin and leptin 26,45 .”
BackgroundRapid, reversible activation of AgRP neurons drives feeding behavior in mice
Krashes, M. J., Koda, S., Ye, C., Rogan, S. C., Adams, A. C., Cusher, D. S., Maratos-Flier, E., Roth, B. L., & Lowell, B. B. (2011) · Journal of Clinical Investigation · doi:10.1172/jci46229 · Cited by 1,578 · see citing works
MiR-33 Contributes to the Regulation of Cholesterol Homeostasis
Rayner, K. J., Suárez, Y., Dávalos, A., Parathath, S., Fitzgerald, M. L., Tamehiro, N., Fisher, E. A., Moore, K. J., & Fernández-Hernando, C. (2010) · Science · doi:10.1126/science.1189862 · Cited by 1,260 · cited 1× · see citing works
“…of miR-33a and miR-33b, are intronic miRNAs encoded within the sterol response binding protein 2 ( SREBP2 ) and SREBP1 genes, respectively 4,5 . miRNA-33a/b provide a critical link between the regulation of cholesterol and fatty acid biosynthesis by SREBPs, and cholesterol ef fl ux,…”
BackgroundSelf-citationAGRP neurons are sufficient to orchestrate feeding behavior rapidly and without training
Aponte, Y., Atasoy, D., & Sternson, S. M. (2011) · Nature Neuroscience · doi:10.1038/nn.2739 · Cited by 1,157 · see citing works
Cell-type-specific isolation of ribosome-associated mRNA from complex tissues
Sanz, E., Yang, L., Su, T., Morris, D. R., McKnight, G. S., & Amieux, P. S. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0907143106 · Cited by 982 · cited 2× · see citing works
“These mice express an unmodi fi ed copy of the core ribosome subunit RPL22 under normal conditions, which is excised in cells expressing CRE, leading to the expression of a modi fi ed RPL22 construct containing multiple HA tags 30,31 .”
BackgroundMicroRNA-33 and the SREBP Host Genes Cooperate to Control Cholesterol Homeostasis
Najafi-Shoushtari, S. H., Kristo, F., Li, Y., Shioda, T., Cohen, D. E., Gerszten, R. E., & Näär, A. M. (2010) · Science · doi:10.1126/science.1189123 · Cited by 957 · cited 5× · see citing works
“…of miR-33a and miR-33b, are intronic miRNAs encoded within the sterol response binding protein 2 ( SREBP2 ) and SREBP1 genes, respectively 4,5 . miRNA-33a/b provide a critical link between the regulation of cholesterol and fatty acid biosynthesis by SREBPs, and cholesterol ef fl ux,…”
BackgroundInfluentialMolecular mechanisms of dietary restriction promoting health and longevity
Green, C. L., Lamming, D. W., & Fontana, L. (2022) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-021-00411-4 · Cited by 714 · cited 1× · see citing works
“On the other hand, increased activity of these cells is associated with calorie restriction, the most robust intervention to promote health-and life-span across species 39 .”
BackgroundUCP2 mediates ghrelin’s action on NPY/AgRP neurons by lowering free radicals
Andrews, Z. B., Liu, Z.-W., Walllingford, N., Erion, D. M., Borok, E., Friedman, J. M., Tschöp, M. H., Shanabrough, M., Cline, G., Shulman, G. I., et al. (2008) · Nature · doi:10.1038/nature07181 · Cited by 710 · see citing works
Self-citationInhibition of miR-33a/b in non-human primates raises plasma HDL and lowers VLDL triglycerides
Rayner, K. J., Esau, C. C., Hussain, F. N., McDaniel, A. L., Marshall, S. M., van Gils, J. M., Ray, T. D., Sheedy, F. J., Goedeke, L., Liu, X., et al. (2011) · Nature · doi:10.1038/nature10486 · Cited by 706 · cited 4× · see citing works
“…response binding protein 2 ( SREBP2 ) and SREBP1 genes, respectively 4,5 . miRNA-33a/b provide a critical link between the regulation of cholesterol and fatty acid biosynthesis by SREBPs, and cholesterol ef fl ux, high-density lipoprotein (HDL) bio-genesis, and fatty acid oxidation pathways 4 – 8 .”
BackgroundInfluentialRayner, K. J., Sheedy, F. J., Esau, C. C., Hussain, F. N., Temel, R. E., Parathath, S., van Gils, J. M., Rayner, A. J., Chang, A. N., Suarez, Y., et al. (2011) · Journal of Clinical Investigation · doi:10.1172/jci57275 · Cited by 690 · cited 3× · see citing works
“Notably, pharmacological inhibition of miR-33 elevates hepatic ABCA1 expression, thereby increasing circulating HDL-C and attenuating the progression of atherosclerosis, highlighting the therapeutic potential of miR-33 inhibitors for the treatment of cardiovascular disease 9,10 .”
BackgroundmiR-33a/b contribute to the regulation of fatty acid metabolism and insulin signaling
Dávalos, A., Goedeke, L., Smibert, P., Ramírez, C. M., Warrier, N. P., Andreo, U., Cirera-Salinas, D., Rayner, K., Suresh, U., Pastor-Pareja, J. C., et al. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1102281108 · Cited by 670 · see citing works
Self-citationmiR-33 links SREBP-2 induction to repression of sterol transporters
Marquart, T. J., Allen, R. M., Ory, D. S., & Baldán, Á. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1005191107 · Cited by 562 · see citing works
Astrocytic Insulin Signaling Couples Brain Glucose Uptake with Nutrient Availability
García‐Cáceres, C., Quarta, C., Varela, L., Gao, Y., Gruber, T., Legutko, B., Jastroch, M., Johansson, P., Ninkovic, J., Yi, C., et al. (2016) · Cell · doi:10.1016/j.cell.2016.07.028 · Cited by 516 · cited 1× · see citing works
“Astrocytes have also been shown to control the activity of central feeding circuits and related behavioral and autonomic outputs 18 – 21 .”
BackgroundSelf-citationAMPK is essential for energy homeostasis regulation and glucose sensing by POMC and AgRP neurons
Claret, M., Smith, M. A., Batterham, R. L., Selman, C., Choudhury, A. I., Fryer, L. G. D., Clements, M., Al‐Qassab, H., Heffron, H., Xu, A. W., et al. (2007) · Journal of Clinical Investigation · doi:10.1172/jci31516 · Cited by 506 · see citing works
Molecular interrogation of hypothalamic organization reveals distinct dopamine neuronal subtypes
Romanov, R. A., Zeisel, A., Bakker, J., Girach, F., Hellysaz, A., Tomer, R., Alpár, A., Mulder, J., Clotman, F., Keimpema, E., et al. (2017) · Nature Neuroscience · doi:10.1038/nn.4462 · Cited by 502 · see citing works
Loss of GABAergic Signaling by AgRP Neurons to the Parabrachial Nucleus Leads to Starvation
Wu, Q., Boyle, M. P., & Palmiter, R. D. (2009) · Cell · doi:10.1016/j.cell.2009.04.022 · Cited by 465 · cited 1× · see citing works
“…predicted targets are involved in functions related to the activation and signaling in AgRP neurons, including GABAergic signaling related genes 32,33 , calcium transport and singaling 34 , and other lipid metabolism related genes associated with cholesterol and ceramide metabolism 35 ,…”
BackgroundIsolation and culture of adult neurons and neurospheres
Brewer, G. J., & Torricelli, J. R. (2007) · Nature Protocols · doi:10.1038/nprot.2007.207 · Cited by 448 · cited 1× · see citing works
“Tissue digestion was performed as previously described 50,51 .”
MethodExpression of miR-33 from an SREBP2 Intron Inhibits Cholesterol Export and Fatty Acid Oxidation*
Gerin, I., Clerbaux, L.-A., Haumont, O., Lanthier, N., Das, A. K., Burant, C. F., Leclercq, I. A., MacDougald, O. A., & Bommer, G. T. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.152090 · Cited by 382 · cited 1× · see citing works
“…been shown to suppress numerous factors involved in mitochondrial biogenesis and function, including AMP-activated protein kinase subunit-a ( Prkaa1 ), peroxisome proliferator-activated receptor gamma, coactivator 1 alpha ( Ppargc1a ), and carnitine palmitoyl-transferase 1 ( Cpt1a ) 6,22 – 25 .”
BackgroundLeptin signaling in astrocytes regulates hypothalamic neuronal circuits and feeding
Kim, J. G., Suyama, S., Koch, M., Jin, S., Argente-Arizon, P., Argente, J., Liu, Z.-W., Zimmer, M. R., Jeong, J. K., Szigeti-Buck, K., et al. (2014) · Nature Neuroscience · doi:10.1038/nn.3725 · Cited by 336 · cited 1× · see citing works
“Mice (at least 3 per group) were euthanized by iso fl urane inhalation and transcardially perfused with freshly prepared 4% PFA and 0.1% glutaraldehyde, as previously reported 19,21 .”
MethodInfluentialFernandez-Hernando, C. F., Suárez, Y., Rayner, K. J., & Moore, K. J. (2010) · Current Opinion in Lipidology · doi:10.1097/mol.0b013e3283428d9d · Cited by 307 · see citing works
Self-citationDietrich, M. O., Liu, Z.-W., & Horvath, T. L. (2013) · Cell · doi:10.1016/j.cell.2013.09.004 · Cited by 306 · cited 1× · see citing works
“Toassesswhethertheincreasedfeeding behavior in miR-33 AgRPiKO mice may be linked to alterations in mitochondrial abundance and function, as we reported previously 26,28,29 , we performed electron microscopical analysis on AgRP neurons (Fig.”
Coppola, A., Liu, Z.-W., Andrews, Z. B., Paradis, E., Roy, M.-C., Friedman, J. M., Ricquier, D., Richard, D., Horvath, T. L., Gao, X.-B., et al. (2007) · Cell Metabolism · doi:10.1016/j.cmet.2006.12.002 · Cited by 295 · cited 1× · see citing works
“Toassesswhethertheincreasedfeeding behavior in miR-33 AgRPiKO mice may be linked to alterations in mitochondrial abundance and function, as we reported previously 26,28,29 , we performed electron microscopical analysis on AgRP neurons (Fig.”
Hypothalamic Agrp Neurons Drive Stereotypic Behaviors beyond Feeding
Dietrich, M. O., Zimmer, M. R., Bober, J., & Horváth, T. L. (2015) · Cell · doi:10.1016/j.cell.2015.02.024 · Cited by 271 · cited 1× · see citing works
“Finally, AgRP neuronal activity was tied to con-trol of the cerebral cortex and complex behaviors 40,41 and their disorders, including anorexia nervosa 42 .”
MicroRNAs in Metabolic Disease
Fernández-Hernando, C., Ramírez, C. M., Goedeke, L., & Suárez, Y. (2013) · Arteriosclerosis, Thrombosis, and Vascular Biology · doi:10.1161/atvbaha.112.300144 · Cited by 257 · cited 1× · see citing works
“…promoting and supporting healthy dietary practices. microRNAs (miRNAs) and other non-coding RNAs have been demonstrated to be critical regulators of numerous physiologic conditions, and to play a key role in a multitude of different diseases, including those associated with metabolic syndrome 1,2 .”
BackgroundSelf-citationArcuate AgRP neurons mediate orexigenic and glucoregulatory actions of ghrelin
Wang, Q., Liu, C., Uchida, A., Chuang, J.-C., Walker, A. K., Liu, T., Osborne-Lawrence, S. L., Mason, B. L., Mosher, C. A., Berglund, E. D., et al. (2013) · Molecular Metabolism · doi:10.1016/j.molmet.2013.10.001 · Cited by 246 · cited 1× · see citing works
“First, mice expressing a tamoxifen-inducible Cre recombinase ( CreERT2 ) in cells expressing AgRP ( Agrp Cre:ERT2 ) 48 were crossed with Rosa26-lox-stop-lox-tdTomato ( Ai14 ; cre-recombinase-dependent expression) mice (Ai14 reporter mice; stock #007914; The Jackson Laboratory, Bar Harbor, ME, USA)…”
Postembryonic ablation of AgRP neurons in mice leads to a lean, hypophagic phenotype
Bewick, G. A., Gardiner, J., Dhillo, W. S., Kent, A. S., White, N. E., Webster, Z., Ghatei, M. A., & Bloom, S. R. (2005) · The FASEB Journal · doi:10.1096/fj.04-3434fje · Cited by 235 · cited 1× · see citing works
“Impairment in the activity of AgRP neurons has been shown to lead to a lean phenotype while activation of AgRP neurons increases feeding and promotes obesity 15 – 17 .”
BackgroundMicroRNA-33 regulates sterol regulatory element-binding protein 1 expression in mice
Horie, T., Nishino, T., Baba, O., Kuwabara, Y., Nakao, T., Nishiga, M., Usami, S., Izuhara, M., Sowa, N., Yahagi, N., et al. (2013) · Nature Communications · doi:10.1038/ncomms3883 · Cited by 230 · cited 3× · see citing works
“Global deletion of miR-33 was found to promote obesity and metabolic dysfunction due to excess feeding 11,12 .”
BackgroundDynamic GABAergic afferent modulation of AgRP neurons
Garfield, A. S., Shah, B. P., Burgess, C. R., Li, M. M., Li, C., Steger, J. S., Madara, J. C., Campbell, J. N., Kroeger, D., Scammell, T. E., et al. (2016) · Nature Neuroscience · doi:10.1038/nn.4392 · Cited by 211 · cited 1× · see citing works
“…predicted targets are involved in functions related to the activation and signaling in AgRP neurons, including GABAergic signaling related genes 32,33 , calcium transport and singaling 34 , and other lipid metabolism related genes associated with cholesterol and ceramide metabolism 35 ,…”
BackgroundNutritive, Post-ingestive Signals Are the Primary Regulators of AgRP Neuron Activity
Su, Z., Alhadeff, A. L., & Betley, J. N. (2017) · Cell Reports · doi:10.1016/j.celrep.2017.11.036 · Cited by 208 · cited 1× · see citing works
“…related to the activation and signaling in AgRP neurons, including GABAergic signaling related genes 32,33 , calcium transport and singaling 34 , and other lipid metabolism related genes associated with cholesterol and ceramide metabolism 35 , suggesting that additional miR-33 targets may…”
BackgroundKarunakaran, D., Thrush, A. B., Nguyen, M.-A., Richards, L., Geoffrion, M., Singaravelu, R., Ramphos, E., Shangari, P., Ouimet, M., Pezacki, J. P., et al. (2015) · Circulation Research · doi:10.1161/circresaha.117.305624 · Cited by 188 · cited 1× · see citing works
“…been shown to suppress numerous factors involved in mitochondrial biogenesis and function, including AMP-activated protein kinase subunit-a ( Prkaa1 ), peroxisome proliferator-activated receptor gamma, coactivator 1 alpha ( Ppargc1a ), and carnitine palmitoyl-transferase 1 ( Cpt1a ) 6,22 – 25 .”
BackgroundRotllan, N., Ramírez, C. M., Aryal, B., Esau, C. C., & Fernández-Hernando, C. (2013) · Arteriosclerosis, Thrombosis, and Vascular Biology · doi:10.1161/atvbaha.113.301732 · Cited by 174 · cited 3× · see citing works
“Notably, pharmacological inhibition of miR-33 elevates hepatic ABCA1 expression, thereby increasing circulating HDL-C and attenuating the progression of atherosclerosis, highlighting the therapeutic potential of miR-33 inhibitors for the treatment of cardiovascular disease 9,10 .”
BackgroundSelf-citationAllen, R. M., Marquart, T. J., Albert, C. J., Suchy, F. J., Wang, D. Q. ‐., Ananthanarayanan, M., Ford, D. A., & Baldán, Á. (2012) · EMBO Molecular Medicine · doi:10.1002/emmm.201201228 · Cited by 159 · see citing works
Regulation of cholesterol and bile acid homeostasis by the CYP7A1/SREBP2/miR-33a axis
Li, T.-G., Francl, J., Boehme, S., & Chiang, J. Y. L. (2013) · Hepatology · doi:10.1002/hep.26427 · Cited by 153 · see citing works
Genetic dissection of the impact of miR-33a and miR-33b during the progression of atherosclerosis
Price, N. L., Rotllan, N., Canfrán-Duque, A., Zhang, X., Pati, P., Arias, N., Moen, J., Mayr, M., Ford, D. A., Baldán, Á., et al. (2017) · Cell reports · doi:10.1016/j.celrep.2017.10.023 · Cited by 129 · cited 1× · see citing works
“These adverse metabolic effects were suf fi cient to offset the bene fi cial effects of miR-33 de fi - ciency on macrophage cholesterol ef fl ux, thereby negating any ben-e fi cial effects on atherosclerosis in the LDLR knockout model of atherosclerosis 13 .”
BackgroundSelf-citationRiboTag: Ribosomal Tagging Strategy to Analyze Cell‐Type‐Specific mRNA Expression In Vivo
Sanz, E., Bean, J. C., Carey, D. P., Quintana, A., & McKnight, G. S. (2019) · Current Protocols in Neuroscience · doi:10.1002/cpns.77 · Cited by 126 · cited 2× · see citing works
“These mice express an unmodi fi ed copy of the core ribosome subunit RPL22 under normal conditions, which is excised in cells expressing CRE, leading to the expression of a modi fi ed RPL22 construct containing multiple HA tags 30,31 .”
BackgroundPrice, N. L., Singh, A. K., Rotllan, N., Goedeke, L., Wing, A., Canfrán-Duque, A., Diaz-Ruiz, A., Araldi, E., Baldán, Á., Camporez, J.-P., et al. (2018) · Cell Reports · doi:10.1016/j.celrep.2018.01.074 · Cited by 110 · cited 4× · see citing works
“Glucose tolerance tests (GTT) were performed following overnight fasting (16h) by intraperitoneal (IP) injection of glucose at a dose of 1 g/kg body weight in mice fed a HFD for 3 months, following standard procedure 12 .”
BackgroundMethodInfluentialSelf-citationCentral Ceramide Signaling Mediates Obesity-Induced Precocious Puberty
Heras, V., Castellano, J. M., Fernandois, D., Velasco, I., Rodríguez-Vázquez, E., Roa, J., Vazquez, M. J., Ruíz-Pino, F., Rubio, M., Pineda, R., et al. (2020) · Cell Metabolism · doi:10.1016/j.cmet.2020.10.001 · Cited by 91 · cited 1× · see citing works
“…AgRP neurons, including GABAergic signaling related genes 32,33 , calcium transport and singaling 34 , and other lipid metabolism related genes associated with cholesterol and ceramide metabolism 35 , suggesting that additional miR-33 targets may also be involved in mediating some of these effects.”
BackgroundGABAergic mechanisms regulated by miR-33 encode state-dependent fear
Jovasevic, V., Corcoran, K. A., Leaderbrand, K., Yamawaki, N., Guedea, A. L., Chen, H. J., Shepherd, G. M. G., & Radulovic, J. (2015) · Nature Neuroscience · doi:10.1038/nn.4084 · Cited by 88 · cited 1× · see citing works
“Other studies have shown that miR-33 in speci fi c subsetsofneuronscanregulatestatedependentmemoryandadaptive thermogenesis through repression of gamma-aminobutyric acid (GABA) A receptor subunits, but an impact on obesity was not observed 37,38 .”
BackgroundPrice, N., Rotllan, N., Zhang, X.-B., Canfrán-Duque, A., Nottoli, T., Suárez, Y., & Fernández-Hernando, C. (2019) · Circulation Research · doi:10.1161/circresaha.118.314415 · Cited by 80 · see citing works
Self-citationAgRP neurons control compulsive exercise and survival in an activity-based anorexia model
Miletta, M. C., İyilikci, O., Shanabrough, M., Šestan-Peša, M., Cammisa, A., Zeiss, C. J., Dietrich, M. O., & Horváth, T. L. (2020) · Nature Metabolism · doi:10.1038/s42255-020-00300-8 · Cited by 79 · cited 1× · see citing works
“Finally, AgRP neuronal activity was tied to con-trol of the cerebral cortex and complex behaviors 40,41 and their disorders, including anorexia nervosa 42 .”
MethodSelf-citationHunger-promoting AgRP neurons trigger an astrocyte-mediated feed-forward autoactivation loop in mice
Varela, L., Stutz, B., Song, J. E., Kim, J. G., Liu, Z.-W., Gao, X., & Horváth, T. L. (2021) · Journal of Clinical Investigation · doi:10.1172/jci144239 · Cited by 75 · cited 3× · see citing works
“The sections were coverslipped and imaged using a Keyence BZ-X700 fl uoresce microscope 20,21 .”
BackgroundMethodInfluentialSelf-citationAhangari, F., Price, N. L., Malik, S., Chioccioli, M., Bärnthaler, T., Adams, T. S., Kim, J., Pradeep, S. P., Ding, S., Cosmos, C., et al. (2023) · JCI Insight · doi:10.1172/jci.insight.158100 · Cited by 70 · see citing works
Self-citationGenetic deficiency or pharmacological inhibition of miR-33 protects from kidney fibrosis
Price, N. L., Miguel, V., Ding, W. J., Singh, A. K., Malik, S., Rotllán, N., Moshnikova, A., Toczek, J., Zeiss, C. J., Sadeghi, M. M., et al. (2019) · JCI Insight · doi:10.1172/jci.insight.131102 · Cited by 67 · see citing works
Self-citationPrice, N. L., Zhang, X., Fernández-Tussy, P., Singh, A. K., Burnap, S. A., Rotllan, N., Goedeke, L., Sun, J., Canfrán-Duque, A., Aryal, B., et al. (2021) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2006478118 · Cited by 50 · cited 5× · see citing works
“…loss of miR-33 in peripheral organs, such as the liver and adipose tissue, that indirectly regulate feeding behavior, did not lead to increased body weight 14 , we nextsoughttodetermineifmiR-33isdirectlyinvolvedinregulatingthe activityoftheAgRPandPOMCneuronsthatpromotesignalsofhunger and satiety.”
BackgroundMethodInfluentialSelf-citationmicroRNA-33 maintains adaptive thermogenesis via enhanced sympathetic nerve activity
Horie, T., Nakao, T., Miyasaka, Y., Nishino, T., Matsumura, S., Nakazeki, F., Ide, Y., Kimura, M., Tsuji, S., Rodriguez, R. R., et al. (2021) · Nature Communications · doi:10.1038/s41467-021-21107-5 · Cited by 49 · cited 2× · see citing works
“Other studies have shown that miR-33 in speci fi c subsetsofneuronscanregulatestatedependentmemoryandadaptive thermogenesis through repression of gamma-aminobutyric acid (GABA) A receptor subunits, but an impact on obesity was not observed 37,38 .”
BackgroundAstrocytic lipid metabolism determines susceptibility to diet-induced obesity
Varela, L., Kim, J. G., Fernández‐Tussy, P., Aryal, B. K., Liu, Z. W., Fernandez-Hernando, C. F., & Horváth, T. L. (2021) · Science Advances · doi:10.1126/sciadv.abj2814 · Cited by 44 · cited 1× · see citing works
“The sections were coverslipped and imaged using a Keyence BZ-X700 fl uoresce microscope 20,21 .”
MethodSelf-citationDrp1 is required for AgRP neuronal activity and feeding
Jin, S., Yoon, N. A., Liu, Z.-W., Song, J. E., Horvath, T. L., Kim, J. D., & Diano, S. (2021) · eLife · doi:10.7554/elife.64351 · Cited by 38 · cited 1× · see citing works
“…in the absence of tamoxifen administration, indicating that recombination was strictly dependent upon tamoxifen-induced Cre recombinase activation 49 . miR-33 loxP/loxP were crossed with AgRP-ERT2 Cre-Ai14 miceto generated mice that wereheterozygous for the miR-33 inducible knockout allele, with…”
BackgroundSelf-citationIDOL regulates systemic energy balance through control of neuronal VLDLR expression
Lee, S. D., Priest, C., Bjursell, M., Gao, J., Arneson, D. V., Ahn, I. S., Diamante, G., van Veen, J. E., Massa, M. G., Calkin, A. C., et al. (2019) · Nature Metabolism · doi:10.1038/s42255-019-0127-7 · Cited by 26 · cited 1× · see citing works
“Tissue digestion was performed as previously described 50,51 .”
MethodHypothalamic miRNAs: emerging roles in energy balance control
Schneeberger, M., Gómez-Valadés, A. G., Ramírez, S., Gomis, R., & Claret, M. (2015) · Frontiers in Neuroscience · doi:10.3389/fnins.2015.00041 · Cited by 24 · see citing works
AgRP neurons control structure and function of the medial prefrontal cortex
Stutz, B., Waterson, M. J., Šestan-Peša, M., Dietrich, M. O., Škarica, M., Šestan, N., Rácz, B., Magyar, A., Sótonyi, P., Liu, Z.-W., et al. (2022) · Molecular Psychiatry · doi:10.1038/s41380-022-01691-8 · Cited by 21 · cited 1× · see citing works
“Finally, AgRP neuronal activity was tied to con-trol of the cerebral cortex and complex behaviors 40,41 and their disorders, including anorexia nervosa 42 .”
MethodCPT1A in AgRP neurons is required for sex-dependent regulation of feeding and thirst
Zagmutt, S., Mera, P., González‐García, I., Ibeas, K., Romero, M. D. M., Obri, A., Martín‐Mur, B., Esteve‐Codina, A., Soler‐Vázquez, M. C., Bastías-Pérez, M., et al. (2023) · Biology of Sex Differences · doi:10.1186/s13293-023-00498-8 · Cited by 14 · cited 1× · see citing works
“Targeted deletion of CPT1 in AgRP neurons resulted in reduced body weight in both sexes, although feeding was only found to be reduced in male mice, while females demonstrated similar feeding but an increase in energy expenditure 47 .”
BackgroundPGC-1α expression in murine AgRP neurons regulates food intake and energy balance
Gill, J. F., Delezie, J., Santos, G., & Handschin, C. (2016) · Molecular Metabolism · doi:10.1016/j.molmet.2016.05.008 · Cited by 12 · see citing works
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Wang, J., Tao, X., Liu, Z., Yan, Y., Cheng, P.-F., Liu, B., Du, H., & Niu, B. (2025) · Pharmacological Research · doi:10.1016/j.phrs.2025.107596 · Cited by 47 · see citing works
Neuronal Regulation of Feeding and Energy Metabolism: A Focus on the Hypothalamus and Brainstem
Chen, J. W., Cai, M., & Zhan, C. (2024) · Neuroscience Bulletin · doi:10.1007/s12264-024-01335-7 · Cited by 34 · see citing works
“Loss of miRNA-33 leads to increased food intake, obesity, and metabolic dysfunction, underscoring its pivotal role in energy regulation [61].”
miR-33 deletion in hepatocytes attenuates MASLD-MASH-HCC progression
Fernández-Tussy, P., Cardelo, M. P., Zhang, H., Sun, J., Price, N. L., Boutagy, N. E., Goedeke, L., Cadena-Sandoval, M., Xirouchaki, C. E., Brown, W., et al. (2024) · JCI Insight · doi:10.1172/jci.insight.168476 · Cited by 21 · see citing works
Self-citationTherapeutic Applications of Poly-miRNAs and miRNA Sponges
Ibáñez-Hernández, M., Avendaño-Portugal, C., Montaño-Samaniego, M., Guttman-Bazbaz, R., & Bravo‐Estupiñan, D. M. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26104535 · Cited by 22 · see citing works
“In another study, miR-33 was deleted in AgRP neurons, leading to metabolic dysregulation and obesity in mice [104]. miR-33b serum levels are potential biomarkers for obesity and hypercholesterolemia [98], as well as possible treatments, underscoring the importance and need for more targeted miRNA…”
Liu, S., Zhuang, S., Li, R., & Duan, H. (2025) · Diabetology & Metabolic Syndrome · doi:10.1186/s13098-025-01683-y · Cited by 18 · see citing works
The power of microRNA regulation—insights into immunity and metabolism
Oliveto, S., Manfrini, N., & Biffo, S. (2025) · FEBS Letters · doi:10.1002/1873-3468.70039 · Cited by 20 · see citing works
“This repression leads to decreased fatty acid oxidation and increased cellular lipid accumulation [54,86,87].”
Intramolecular DNA Wheel Construction for Highly Sensitive Electrochemical Detection of miRNA
Qu, X., Han, Y., Huang, Q., & Miao, P. (2025) · Nano Letters · doi:10.1021/acs.nanolett.4c05127 · Cited by 18 · see citing works
MicroRNAs in metabolic dysfunction‐associated diseases: Pathogenesis and therapeutic opportunities
Ma, N., Tan, J., Chen, Y., Liu, Y., Li, M., & He, Y. (2024) · The FASEB Journal · doi:10.1096/fj.202401464r · Cited by 20 · see citing works
DNA Nanostructure Disintegration-Assisted SPAAC Ligation for Electrochemical Biosensing
Wang, T., Zheng, X., Chai, H., et al. (2024) · Nano Letters · doi:10.1021/acs.nanolett.4c03394 · Cited by 14 · see citing works
Zacharjasz, J., Sztachera, M., Smuszkiewicz, M., & Piwecka, M. (2024) · FEBS Letters · doi:10.1002/1873-3468.14948 · Cited by 10 · see citing works
Endoplasmic reticulum Nogo drives AgRP neuronal activation and feeding behavior
Jin, S., Yoon, N. A., Wei, M., Worgall, T. S., Rubinelli, L., Horváth, T. L., Min, W., Diano, N., Lorenzo, A. D., & Diano, S. (2025) · Cell Metabolism · doi:10.1016/j.cmet.2025.04.005 · Cited by 9 · see citing works
Masoumi‐Ardakani, Y., Eghbalian, M., Fallah, H., Jafari, A., & Shahouzehi, B. (2025) · BMC Endocrine Disorders · doi:10.1186/s12902-025-01849-9 · Cited by 7 · see citing works
Rapps, K., Marco, A., Pe’er-Nissan, H., Kisliouk, T., Stemp, G., Yadid, G., Weller, A., & Meiri, N. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25137188 · Cited by 6 · see citing works
“In the satiety centers, in the hypothalamus, microRNA-33 has been demonstrated to controls hunger signaling in hypothalamic AgRP neurons [46].”
BackgroundHorie, T., Baba, O., Nishino, T., Yamashita, Y., Tsujisaka, Y., & Ono, K. (2026) · Journal of Atherosclerosis and Thrombosis · doi:10.5551/jat.rv22045 · Cited by 5 · see citing works
“MiR-33a has been shown to control hunger signaling in hypothalamic AgRP neurons possibly through several miR-33 target genes such as PRKAA1 , Ppargc1a , CPT1a and CROT ; thus, loss of miR-33a leads to increased feeding, obesity, and metabolic dysfunction in mice 41) .”
Huang, K., Pokhrel, A., Echesabal-Chen, J., Scott, J., Bruce, T., Jo, H., & Stamatikos, A. (2025) · Medicina · doi:10.3390/medicina61020329 · Cited by 4 · see citing works
“Though we and other laboratories have extensively evaluated the atherogenic effects of miR-33a in several cell types [39,44,45,51,52,55,81–83], these studies have predominantly focused on miR-33a-5p, and scant data have been published on assessing whether miR-33a-3p plays an atherogenic role in…”
Röhrborn, K., Hoffmann, A., Lorenz, A., et al. (2025) · Molecular Metabolism · doi:10.1016/j.molmet.2025.102265 · Cited by 2 · see citing works
Shnayder, N. A., Pekarets, N. I., Pekarets, N. I., Дмитренко, Д. В., Владимировна, Г. В., Петрова, М. М., Al-Zamil, M., & Nasyrova, R. F. (2025) · Journal of Clinical Medicine · doi:10.3390/jcm14072432 · Cited by 2 · see citing works
“MiR-33 suppresses appetite by reducing the activity of AgRP neurons in the hypothalamus [55] but at the same time reduces responsiveness to leptin [60].”
InfluentialShnayder, N. A., Nasyrova, R. F., Pekarets, N. I., Владимировна, Г. В., & Петрова, М. М. (2025) · Safety and Risk of Pharmacotherapy · doi:10.30895/2312-7821-2025-478 · Cited by 2 · see citing works
Emerging role of exosomal-microRNA in obesity
Moncy, A. T. P., Das, S., & Vasanthi, H. R. (2025) · Current Opinion in Physiology · doi:10.1016/j.cophys.2025.100827 · Cited by 1 · see citing works
Sun, K., & Sun, Y. (2025) · Next research. · doi:10.1016/j.nexres.2025.100484 · Cited by 1 · see citing works
Shnayder, N. A., Nasyrova, R. F., Pekarets, N. I., Владимировна, Г. В., & Петрова, М. М. (2025) · Safety and Risk of Pharmacotherapy · doi:10.30895/2312-7821-2025-499 · Cited by 1 · see citing works
Exploring Reward Sensitivity as a Central Mechanism in Binge-Eating Behavior
Minari, T. P., Filho, G. M. D. A., & Pisani, L. P. (2025) · Journal of Nutrition · doi:10.1016/j.tjnut.2025.101294 · Cited by 1 · see citing works
Targeting Gβγ subunits in hypothalamic AgRP neurons to treat obesity
Ye, X., Xiong, X., Wang, X., Wang, Y., Shen, Y. H., Zhang, H., Zhang, R., Chen, L., Zhang, P., Zhang, Y., et al. (2026) · Metabolism · doi:10.1016/j.metabol.2026.156569 · Cited by 1 · see citing works
RNA-based approaches in the diagnosis and treatment of obesity
Parekh, K., & Sarker, G. (2026) · Frontiers in Pharmacology · doi:10.3389/fphar.2026.1882300
“A recent study supports a cell-type-specific role for miRNAs in this context (Price et al., 2024).”
Central epigenetic mechanisms of overeating and thermal regulation
Meiri, N., & Weller, A. (2026) · Handbook of clinical neurology · doi:10.1016/b978-0-443-19043-8.00020-7
- Authors
- Price, N. L., Fernández-Tussy, P., Varela, L., Cardelo, M. P., Shanabrough, M., Aryal, B., de Cabo, R., Suárez, Y., Horvath, T. L., & Fernández-Hernando, C.
- Affiliations
- National Institutes of Health (US)
- Ikerbasque (ES)
- Yale University (US)
- ORCID
- Venue
- Nature Communications
- Published
- 2024-03-08
- Volume
- 15
- Issue
- 1
- Pages
- 2131-2131
- ISSN
- 2041-1723 (ISSN-L)
- PMC
- PMC10923783
- OpenAlex
- W4392598126
- Semantic Scholar
- 9a340c515c38cfe3bac32f5162dee9e67eff0e5a
- Cited by
- 25
- References
- 53
- Citations by year
- 2026: 3 · 2025: 16 · 2024: 6
- FWCI
- 5.39
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Nature Communications (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (R35HL135820)
- American Heart Association (20TPA35490416, 874771)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
- Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
- Keywords
- miR-33, microRNA, AgRP neurons, hypothalamus, feeding behavior, obesity, metabolic dysfunction, mitochondrial biogenesis, fatty acid metabolism, non-coding RNA, bioenergetics
- MeSH terms
- Animals, Hunger, Hypothalamus, Neurons, Obesity, MicroRNAs, Mice, Agouti-Related Protein
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