The DOI matches its Crossref record; 57 of the 57 references it cites were found in a registry or an index.
Characteristics and mechanisms of hypothalamic neuronal fatty acid sensing
Open accessAbstract
We assessed the mechanisms by which specialized hypothalamic ventromedial nucleus (VMN) neurons utilize both glucose and long-chain fatty acids as signaling molecules to alter their activity as a potential means of regulating energy homeostasis. Fura-2 calcium (Ca 2+) and membrane potential dye imaging, together with pharmacological agents, were used to assess the mechanisms by which oleic acid (OA) alters the activity of dissociated VMN neurons from 3- to 4-wk-old rats. OA excited up to 43% and inhibited up to 29% of all VMN neurons independently of glucose concentrations. In those neurons excited by both 2.5 mM glucose and OA, OA had a concentration-dependent effective excitatory concentration (EC 50) of 13.1 nM. Neurons inhibited by both 2.5 mM glucose and OA had an effective inhibitory concentration (IC 50) of 93 nM. At 0.5 mM glucose, OA had markedly different effects on these same neurons. Inhibition of carnitine palmitoyltransferase, reactive oxygen species formation, long-chain acetyl-CoA synthetase and ATP-sensitive K+channel activity or activation of uncoupling protein 2 (UCP2) accounted for only ∼20% of OA's excitatory effects and ∼40% of its inhibitory effects. Inhibition of CD36, a fatty acid transporter that can alter cell function independently of intracellular fatty acid metabolism, reduced the effects of OA by up to 45%. Thus OA affects VMN neuronal activity through multiple pathways. In glucosensing neurons, its effects are glucose dependent. This glucose-OA interaction provides a potential mechanism whereby such “metabolic sensing” neurons can respond to differences in the metabolic states associated with fasting and feeding.
Overview
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
Verification
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?
In the citing paper
“However, basal levels of FAO enzymes and FA transport proteins (such as FATP-1, FATP-4, and FAT/CD36) are expressed in hypothalamic neurons ([93](#B93), [95](#B95)).”
From Mitochondrial fatty acid oxidation in obesity (2013) · cites this paper as [95]
In the citing paper
“and the capacity of hypothalamic neurons to sense glucose and FFA simultaneously and to integrate other nutritional and hormonal inputs ([95](#B95), [99](#B99))”
From Mitochondrial fatty acid oxidation in obesity (2013) · cites this paper as [95]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Sokoloff, L., Reivich, M., Kennedy, C., Rosiers, M. H. D., Patlak, C. S., Pettigrew, K. D., Sakurada, O., & Shinohara, M. (1977) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.1977.tb10649.x · Cited by 6,000
Ischemic Cell Death in Brain Neurons
Lipton, P. (1999) · Physiological Reviews · doi:10.1152/physrev.1999.79.4.1431 · Cited by 3,043
Neural activity triggers neuronal oxidative metabolism followed by astrocytic glycolysis
Kasischke, K. A., Vishwasrao, H. D., Fisher, P. J., Zipfel, W. R., & Webb, W. W. (2004) · Science · doi:10.1126/science.1096485 · Cited by 742
UCP2 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
Glucose sensing by POMC neurons regulates glucose homeostasis and is impaired in obesity
Parton, L. E., Ye, C. P., Coppari, R., Enriori, P. J., Choi, B., Zhang, C.-Y., Xu, C., Vianna, C. R., Balthasar, N., Lee, C. E., et al. (2007) · Nature · doi:10.1038/nature06098 · Cited by 700
Laugerette, F. (2005) · Journal of Clinical Investigation · doi:10.1172/jci25299 · Cited by 678
Central Administration of Oleic Acid Inhibits Glucose Production and Food Intake
Obici, S., Feng, Z., Morgan, K., Stein, D., Karkanias, G., & Rossetti, L. (2002) · Diabetes · doi:10.2337/diabetes.51.2.271 · Cited by 654
Glucose and Osmosensitive Neurones of the Rat Hypothalamus
Oomura, Y., Ono, T., Ooyama, H., & Wayner, M. J. (1969) · Nature · doi:10.1038/222282a0 · Cited by 597
Obici, S., Feng, Z., Arduini, A., Conti, R., & Rossetti, L. (2003) · Nature Medicine · doi:10.1038/nm873 · Cited by 548
Structure of Biological Membranes
Korn, E. D. (1966) · Science · doi:10.1126/science.153.3743.1491 · Cited by 547
Cited by
Sorted by citations
Schönfeld, P., & Reiser, G. (2013) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1038/jcbfm.2013.128 · Cited by 457
Hypothalamic nutrient sensing in the control of energy homeostasis
Blouet, C., & Schwartz, G. J. (2009) · Behavioural Brain Research · doi:10.1016/j.bbr.2009.12.024 · Cited by 343
Lipid Processing in the Brain: A Key Regulator of Systemic Metabolism
Bruce, K. D., Zsombok, A., & Eckel, R. H. (2017) · Frontiers in Endocrinology · doi:10.3389/fendo.2017.00060 · Cited by 279
“Similarly, inhibition of FAS activity by central administration of the pharmacological FAS inhibitor C75 has been shown to reduce food intake (73) and to elevate malonyl-CoA levels (74).”
BackgroundInfluentialTaste of Fat: A Sixth Taste Modality?
Besnard, P., Passilly‐Degrace, P., & Khan, N. A. (2016) · Physiological Reviews · doi:10.1152/physrev.00002.2015 · Cited by 269
“By its expression in the gustatory papillae (105), as well as the small intestine (160) and hypothalamus (106), CD36 might also be the cornerstone of a “functional continuum” along the oro-intestinal-brain axis, responsible for a real-time adaptation of food selection and the subsequent metabolic fate of dietary lipid…”
BackgroundMitochondrial fatty acid oxidation in obesity
Serra, D., Mera, P., Malandrino, M. I., Mir, J. F., & Herrero, L. (2013) · Antioxidants & Redox Signaling · doi:10.1089/ars.2012.4875 · Cited by 246
“Nonetheless, the direct correlation observed between fasting and FFA levels (156) and the capacity of hypothalamic neurons to sense glucose and FFA simultaneously and to integrate other nutritional and hormonal inputs (95, 99) seem to throw light on how important FAO really is in hypothalamic nuclei.”
Kuda, O., Pietka, T., Demianová, Z., Kudová, E., Cvačka, J., Kopecký, J., & Abumrad, N. A. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.m113.473298 · Cited by 218
Delgado, M. J., Cerdá‐Reverter, J. M., & Soengas, J. L. (2017) · Frontiers in Neuroscience · doi:10.3389/fnins.2017.00354 · Cited by 171
“…the increased binding to fatty acid translocase (FAT/CD36) induced by increased levels of LCFA results in the modulation of transcription factors like sterol regulatory element-binding protein type 1c (SREBP1c), and peroxisome proliferator-activated receptor type α (PPARα) (Le Foll et al., 2009).”
BackgroundInfluentialBouret, S., Levin, B. E., & Ozanne, S. E. (2015) · Physiological Reviews · doi:10.1152/physrev.00007.2014 · Cited by 157
Self-citationMartin, C., Chevrot, M., Poirier, H., Passilly‐Degrace, P., Niot, I., & Besnard, P. (2011) · Physiology & Behavior · doi:10.1016/j.physbeh.2011.02.029 · Cited by 162
Metabolic Sensing and the Brain: Who, What, Where, and How?
Levin, B. E., Magnan, C., Dunn-Meynell, A. A., & Foll, C. L. (2011) · Endocrinology · doi:10.1210/en.2011-0194 · Cited by 147
“Importantly, most neurons use fatty acids primarily for membrane production rather than as a metabolic substrate (58, 59), and only nanomolar concentrations of fatty acid are required to alter the activity of fatty acid sensing neurons in the absence of astrocytes (39).”
BackgroundSelf-citationCircadian Rhythms in Diet-Induced Obesity
Engin, A. (2017) · Advances in experimental medicine and biology · doi:10.1007/978-3-319-48382-5_2 · Cited by 149
Nutrient Sensing Systems in Fish: Impact on Food Intake Regulation and Energy Homeostasis
Conde‐Sieira, M., & Soengas, J. L. (2017) · Frontiers in Neuroscience · doi:10.3389/fnins.2016.00603 · Cited by 147
“…are also implicated in the regulation of energy homeostasis through processes other than food intake (Levin, 2006; Blouet and Schwartz, 2010; Morton et al., 2014), such as hormone secretion and energy expenditure (Morgan et al., 2004; Pocai et al., 2005; Le Foll et al., 2009; Roh et al., 2016).”
BackgroundThe regulation of food intake in mammalian hibernators: a review
Florant, G. L., & Healy, J. E. (2011) · Journal of Comparative Physiology B · doi:10.1007/s00360-011-0630-y · Cited by 121
“The conclusion from several recent studies suggests that FA can alter many hypothalamic activities including calcium signaling (Le Foll et al. 2009b), FA transporters (Migrenne et al. 2011), receptors, and potassium channels (Le Foll et al. 2009a).”
BackgroundRegulation of Hypothalamic Neuronal Sensing and Food Intake by Ketone Bodies and Fatty Acids
Foll, C. L., Dunn-Meynell, A. A., Miziorko, H. M., & Levin, B. E. (2013) · Diabetes · doi:10.2337/db13-1090 · Cited by 125
“In fact, this method correlates well with changes in membrane potential induced by FA (18,21), but we cannot state with certainty that this necessarily correlates with changes in neuronal activity.”
InfluentialSelf-citationFatty acid-induced astrocyte ketone production and the control of food intake
Foll, C. L., & Levin, B. E. (2016) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00113.2016 · Cited by 107
Self-citationKuda, O., Jenkins, C. M., Skinner, J. R., Moon, S. H., Su, X., Gross, R. W., & Abumrad, N. A. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.232975 · Cited by 90
FAT/CD36: A Major Regulator of Neuronal Fatty Acid Sensing and Energy Homeostasis in Rats and Mice
Foll, C. L., Dunn-Meynell, A. A., Musatov, S., Magnan, C., & Levin, B. E. (2013) · Diabetes · doi:10.2337/db12-1689 · Cited by 90
“We previously showed that ;50% of the OA-induced alterations in [Ca]i oscillations were paralleled by alterations in membrane potential (5).”
BackgroundMethodResultInfluentialSelf-citationBrain lipid sensing and the neural control of energy balance
Magnan, C., Levin, B. E., & Luquet, S. H. (2015) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2015.09.019 · Cited by 96
Self-citationAmylin-Induced Central IL-6 Production Enhances Ventromedial Hypothalamic Leptin Signaling
Foll, C. L., Johnson, M. D., Dunn-Meynell, A. A., Boyle, C. N., Lutz, T. A., & Levin, B. E. (2014) · Diabetes · doi:10.2337/db14-0645 · Cited by 87
“Slices were placed in RNA Later (Ambion, Grand Island, NY), the VMH was punched under microscopic guidance, and mRNA expression was assayed by quantitative reverse transcriptase PCR (QPCR; Applied Biosystems, Grand Island, NY) (28,29).”
MethodSelf-citationSoengas, J. L. (2014) · General and Comparative Endocrinology · doi:10.1016/j.ygcen.2014.01.015 · Cited by 85
Cardinal, P., André, C., Quarta, C., Bellocchio, L., Clark, S., Elie, M., Lesté-Lasserre, T., Maître, M., Gonzales, D., Cannich, A., et al. (2014) · Molecular Metabolism · doi:10.1016/j.molmet.2014.07.004 · Cited by 96
Acyl Coenzyme A Thioesterase 7 Regulates Neuronal Fatty Acid Metabolism To Prevent Neurotoxicity
Ellis, J. M., Wong, G. W., & Wolfgang, M. J. (2013) · Molecular and Cellular Biology · doi:10.1128/mcb.01548-12 · Cited by 85
“Free fatty acids are known to elicit a response from a subset of neurons in culture (47, 48), and when injected into the lateral ventricles, free fatty acids affect animal behavior and physiology (45, 46).”
BackgroundSchwinkendorf, D. R., Tsatsos, N. G., Gosnell, B. A., & Mashek, D. G. (2010) · International Journal of Obesity · doi:10.1038/ijo.2010.159 · Cited by 81
Nutrient Sensing: Another Chemosensitivity of the Olfactory System
Julliard, A., Koborssy, D. A., Fadool, D., & Palouzier-Paulignan, B. (2017) · Frontiers in Physiology · doi:10.3389/fphys.2017.00468 · Cited by 67
“In the hypothalamus, it has been postulated that binding of FAs to CD36 alters neuronal activity in a manner analogous to that utilized for fat perception by taste receptor cells (Le Foll et al., 2009).”
BackgroundInfluentialCanosa, L. F., & Bertucci, J. I. (2020) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2020.111029 · Cited by 72
Hypothalamic lipotoxicity and the metabolic syndrome
de Morentin, P. B. M., Varela, L., Fernø, J., Nogueiras, R., Diéguez, C., & López, M. (2009) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2009.09.016 · Cited by 73
“treatment [91,98] and they are also dependent of glucose levels [69,141].”
BackgroundLibrán-Pérez, M., Polakof, S., López‐Patiño, M. A., Míguez, J. M., & Soengas, J. L. (2012) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00070.2012 · Cited by 66
Taïb, B., Bouyakdan, K., Hryhorczuk, C., Rodaros, D., Fulton, S., & Alquier, T. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.m113.506238 · Cited by 65
“In agreement with this idea, etomoxir had a minor effect on oleateinduced calciummobilization in ventromedial nucleus neurons (67).”
BackgroundPathophysiology of Lipid Droplets in Neuroglia
Smolič, T., Zorec, R., & Vardjan, N. (2021) · Antioxidants · doi:10.3390/antiox11010022 · Cited by 73
McFadden, J. W., Aja, S. M., Li, Q., Bandaru, V. V. R., Kim, E. K., Haughey, N. J., Kuhajda, F. P., & Ronnett, G. V. (2014) · PLoS ONE · doi:10.1371/journal.pone.0115642 · Cited by 64
“However, it is important to note that hypothalamic neurons have basal expression of FA oxidative enzymes and transport proteins [56], and equal levels of CPT-1a expression have been demonstrated in cultured neurons versus astrocytes [35].”
BackgroundBrain lipid sensing and nervous control of energy balance
Migrenne, S., Le Foll, C., Levin, B. E., & Magnan, C. (2011) · Diabetes & Metabolism · doi:10.1016/j.diabet.2010.11.001 · Cited by 58
“Le métabolisme intracellulaire des AGL semble être aussi important pour elayer leurs effets mais des données récentes indiquent que dans la moitié au moins des neurones sensibles au AGL, ce soit un mécanisme épendant du transporteur membranaire des acides gras, FAT/CD36, qui soit impliqué.”
BackgroundInfluentialSelf-citationSupraoptic oxytocin and vasopressin neurons function as glucose and metabolic sensors
Song, Z., Levin, B. E., Stevens, W., & Sladek, C. D. (2014) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00520.2013 · Cited by 58
Self-citationLipid sensing in the brain and regulation of energy balance
Moullé, V. S., Picard, A., Foll, C. L., Levin, B. E., & Magnan, C. (2013) · Diabetes & Metabolism · doi:10.1016/j.diabet.2013.10.001 · Cited by 65
“Dissociated neurons from the hypothalamic ventromedial nucleus (VMN) of rats, for example, express mRNA for FA transport proteins (FATP)-1 and -4 and for the FA transporter/receptor FAT/CD36 [7,16].”
BackgroundInfluentialSelf-citationLevin, B. E. (2010) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2010.02.005 · Cited by 59
Self-citationTracey, T. J., Kirk, S. E., Steyn, F. J., & Ngo, S. T. (2020) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2020.08.012 · Cited by 57
Librán-Pérez, M., Otero-Rodiño, C., López‐Patiño, M. A., Míguez, J. M., & Soengas, J. L. (2014) · Physiology & Behavior · doi:10.1016/j.physbeh.2014.02.061 · Cited by 55
Tanycytes and a differential fatty acid metabolism in the hypothalamus
Hofmann, K., Lamberz, C., Piotrowitz, K., Offermann, N., But, D., Scheller, A., Al‐Amoudi, A., & Kuerschner, L. (2016) · Glia · doi:10.1002/glia.23088 · Cited by 56
“…231 transport protein CD36, neuronal lipoprotein lipase, carnitine palmitoyltransferase and fatty acid oxidation has been identified (Cruciani-Guglielmacci et al., 2004; Gao et al., 2011; Le Foll et al., 2009, 2013; Moulle et al., 2013; Obici et al., 2003; Wang et al., 2011; Wolfgang et al., 2006).”
BackgroundA Neural basis for Octanoic acid regulation of energy balance
Haynes, V. R., Michael, N. J., van den Top, M., Zhao, F., Brown, R. D., Souza, D. P. D., Dodd, G. T., Spanswick, D. C., & Watt, M. J. (2020) · Molecular Metabolism · doi:10.1016/j.molmet.2020.01.002 · Cited by 52
Ross, R., Rossetti, L., Lam, T. K. T., & Schwartz, G. J. (2010) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00190.2010 · Cited by 49
“LCFA may enter neurons by flip-flop mechanisms (19, 21) or, alternatively, rely on the neuronal expression of fatty acid-binding proteins (25), which are regulated by transcription factors activated by LCFA (50).”
BackgroundThe multiple roles of fatty acid handling proteins in brain
Moullé, V. S. F., Cansell, C., Luquet, S., & Cruciani-Guglielmacci, C. (2012) · Frontiers in Physiology · doi:10.3389/fphys.2012.00385 · Cited by 49
“…et al., 2009). www.frontiersin.org September 2012 | Volume 3 | Article 385 | 3 In addition, studies suggest that hypothalamic FA sensitive neurons are dependent on the metabolic state and display different responses during fasting versus overfed state (Le Foll et al., 2009; Migrenne et al., 2011).”
BackgroundLibrán-Pérez, M., López‐Patiño, M. A., Míguez, J. M., & Soengas, J. L. (2013) · PLoS ONE · doi:10.1371/journal.pone.0059507 · Cited by 46
“The concentrations of the different agents used were those previously used in fish [17,21,22] and mammals [1,23,24].”
BackgroundResultInfluentialNon-Neuronal Cells in the Hypothalamic Adaptation to Metabolic Signals
Freire‐Regatillo, A., Argente-Arizón, P., Argente, J., García‐Segura, L. M., & Chowen, J. A. (2017) · Frontiers in Endocrinology · doi:10.3389/fendo.2017.00051 · Cited by 48
Hypothalamic control of energy and glucose metabolism
Sisley, S. R., & Sandoval, D. A. (2011) · Reviews in Endocrine and Metabolic Disorders · doi:10.1007/s11154-011-9189-x · Cited by 45
“show that oleic acid neuronal activation in the VMN involves carnitine palmitoyl CoA transferase (CPT-1), fatty acid transport proteins, long-chain fatty acid CoA synthetase, and KATP channels [66].”
Fatty acid sensing in the gut and the hypothalamus: In vivo and in vitro perspectives
Duca, F. A., & Yue, J. T. Y. (2014) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2014.09.022 · Cited by 46
“…synthesis, such as long-chain ACS, CPT-1a and CPT-1c, uncoupling protein 2, ACC1 and ACC2, fatty acid synthase (FAS), MCD, and PDHa1 and PDHa2 (Le Foll et al., 2009; Taib et al., 2013), providing some evidence to support in vivo findings that fatty acids can be sensed and metabolized in neurons…”
Foll, C. L. (2019) · Frontiers in Physiology · doi:10.3389/fphys.2019.01036 · Cited by 46
Foll, C. L., Irani, B. G., Magnan, C., Dunn-Meynell, A. A., & Levin, B. E. (2009) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00370.2009 · Cited by 42
Self-citationCD36 is expressed in a defined subpopulation of neurons in the olfactory epithelium
Xavier, A. M., Ludwig, R. G., Nagai, M. H., de Almeida, T. J., Watanabe, H. M., Hirata, M. Y., Rosenstock, T. R., Papes, F., Malnic, B., & Glezer, I. (2016) · Scientific Reports · doi:10.1038/srep25507 · Cited by 40
“For instance, it was shown that a subpopulation of glucose-responsive hypothalamic neurons senses fatty acids through CD36 38,39 .”
Gut fat sensing in the negative feedback control of energy balance — Recent advances
Schwartz, G. J. (2011) · Physiology & Behavior · doi:10.1016/j.physbeh.2011.05.003 · Cited by 41
“CD36 is also expressed by neurons, including ventromedial (VMH) hypothalamic neurons where it mediates oleic acid-induced signaling independently of fatty acid metabolism [19], suggesting that it may act centrally as a lipid sensor important in the control of energy balance.”
BackgroundGao, S., Casals, N., Keung, W., Moran, T. H., & Lopaschuk, G. D. (2013) · Physiology & Behavior · doi:10.1016/j.physbeh.2013.03.030 · Cited by 40
“Moreover, fatty acid sensing neurons have been identified in VMN [34].”
BackgroundFang, X.-L., Zhu, X., Chen, S., Zhang, Z., Zeng, Q.-J., Deng, L., Peng, J., Yu, J., Wang, L., Wang, S., et al. (2014) · Poultry Science · doi:10.3382/ps.2014-04047 · Cited by 39
“…from https://academic.oup.com/ps/article-abstract/93/11/2841/2730468 by guest on 29 July 2018 hypothalamic long-chain acyl-CoA (LC-CoA) are associated with regulation of feed intake (Obici et al., 2002; Gao et al., 2007; Lopez et al., 2007; Lopez and Vidal-Puig, 2008; Le Foll et al., 2009).”
BackgroundEffect of dietary fatty acid composition on food intake, triglycerides, and hypothalamic peptides
Barson, J. R., Karatayev, O., Gaysinskaya, V. A., Chang, G., & LEIBOWITZ, S. F. (2011) · Regulatory Peptides · doi:10.1016/j.regpep.2011.08.012 · Cited by 38
“Previous research has shown that certain fatty acids, specifically the long-chain unsaturated fatty acid oleic acid, can decrease expression of both NPY and AgRP [61] but that this same fatty acid differentially affects hypothalamic neurons, stimulating the activity of some while inhibiting others [59].”
BackgroundBrain lipoprotein lipase as a regulator of energy balance
Cruciani‐Guglielmacci, C., & Magnan, C. (2017) · Biochimie · doi:10.1016/j.biochi.2017.07.012 · Cited by 37
Self-citationFoll, C. L., Dunn-Meynell, A. A., & Levin, B. E. (2014) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00367.2014 · Cited by 38
“2, A and B) and glucose and insulin AUCs were increased by 118% and 148%, respectively (Table 1).”
MethodInfluentialSelf-citationFatty Acid Transporter CD36 Mediates Hypothalamic Effect of Fatty Acids on Food Intake in Rats
Moullé, V. S., Foll, C. L., Philippe, E., Kassis, N., Rouch, C., Marsollier, N., Bui, L. C., Guissard, C., Dairou, J., Lorsignol, A., et al. (2013) · PLoS ONE · doi:10.1371/journal.pone.0074021 · Cited by 39
“At least 50% of the FA sensing in VMH neurons was attributable to the interaction of long chain FA with CD36, while only ,20% was attributable to intracellular metabolism of FA, including the inhibition of long chain FA acylCoA synthase (ACS) with triacsin C [14].”
BackgroundInfluentialSelf-citationConde‐Sieira, M., Bonačić, K., Velasco, C., Valente, L. M. P., Morais, S., & Soengas, J. L. (2015) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00386.2015 · Cited by 37
Otlivanchik, O., Foll, C. L., & Levin, B. E. (2014) · Diabetes · doi:10.2337/db14-0671 · Cited by 32
“Given these in vivo findings, we next explored the effects of 5-HT on PFH neuronal excitability using fura-2 calcium imaging in dissociated PFH neurons [15, 30].”
BackgroundMethodSelf-citationOleic Acid in the Ventral Tegmental Area Inhibits Feeding, Food Reward, and Dopamine Tone
Hryhorczuk, C., Sheng, Z., Décarie-Spain, L., Giguère, N., Ducrot, C., Trudeau, L., Routh, V. H., Alquier, T., & Fulton, S. (2017) · Neuropsychopharmacology · doi:10.1038/npp.2017.203 · Cited by 33
Misalignment of Circadian Rhythms in Diet-Induced Obesity
Engin, A. (2024) · Advances in experimental medicine and biology · doi:10.1007/978-3-031-63657-8_2 · Cited by 35
Mechanisms Mediating the Actions of Fatty Acids in the Hypothalamus
Dragano, N. R. V., Monfort‐Pires, M., & Velloso, L. A. (2019) · Neuroscience · doi:10.1016/j.neuroscience.2019.10.012 · Cited by 31
Foll, C. L., Dunn-Meynell, A. A., Miziorko, H. M., & Levin, B. E. (2015) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00015.2015 · Cited by 30
Self-citationLaperrousaz, E., Moullé, V. S., Denis, R., Kassis, N., Berland, C., Colsch, B., Fioramonti, X., Philippe, E., Lacombe, A., Vanacker, C., et al. (2017) · Diabetologia · doi:10.1007/s00125-017-4282-7 · Cited by 30
“The present work tested the hypothesis that LPL in the mediobasal hypothalamus (MBH, defined as ventromedial hypothalamus plus arcuate nucleus [11]) participates in the regulation of systemic energy balance, as up to 70% of its neurons are fatty acid sensitive [4, 12].”
Self-citationPhysiological and pathophysiological implications of lipid sensing in the brain
Picard, A., Moullé, V. S., Foll, C. L., Cansell, C., Véret, J., Coant, N., Stunff, H. L., Migrenne, S., Luquet, S. H., Cruciani‐Guglielmacci, C., et al. (2014) · Diabetes Obesity and Metabolism · doi:10.1111/dom.12335 · Cited by 32
“They also express enzymes for de novo FA synthesis such as FA synthase (FAS) [18].”
BackgroundInfluentialSelf-citationRiel, E. B., Jürs, B. C., Cordeiro, S., Musinszki, M. A., Schewe, M., & Baukrowitz, T. (2021) · The Journal of General Physiology · doi:10.1085/jgp.202112989 · Cited by 28
The hypothalamic regulation of metabolic adaptations to exercise
Fujikawa, T., Castorena, C. M., Lee, S., & Elmquist, J. K. (2017) · Journal of Neuroendocrinology · doi:10.1111/jne.12533 · Cited by 28
Hypothalamic Nutrient Sensing and Energy Balance
Moran, T. H. (2009) · Forum of nutrition/Bibliotheca Nutritio et dieta · doi:10.1159/000264397 · Cited by 29
The (dys)regulation of energy storage in obesity
Levin, B. E., Geary, N., & Lutz, T. A. (2025) · Physiological Reviews · doi:10.1152/physrev.00002.2024 · Cited by 27
Self-citationHeeley, N., Kirwan, P., Darwish, T., Arnaud, M., Evans, M. L., Merkle, F. T., Reimann, F. M., Gribble, F. M., & Blouet, C. (2018) · Molecular Metabolism · doi:10.1016/j.molmet.2018.01.021 · Cited by 23
Dietary lipids as regulators of reward processes: multimodal integration matters
Berland, C., Small, D. M., Luquet, S. H., & Gangarossa, G. (2021) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2021.05.008 · Cited by 27
Martins, N., Magalhães, R., Vieria, L., Couto, A., Serra, C. R., Maia, M. R. G., Fonseca, A. J. M., Cabrita, A. R. J., Pousão‐Ferreira, P., Castro, C., et al. (2023) · Aquaculture · doi:10.1016/j.aquaculture.2023.739870 · Cited by 21
Unraveling brain palmitic acid: Origin, levels and metabolic fate
Smith, M. E., & Bazinet, R. P. (2024) · Progress in Lipid Research · doi:10.1016/j.plipres.2024.101300 · Cited by 22
Stunff, H. L., Coant, N., Migrenne, S., & Magnan, C. (2013) · Expert Opinion on Therapeutic Targets · doi:10.1517/14728222.2013.768233 · Cited by 23
“is unlikely that neurons derive much of their energy supply from FFAs, these same neurons do express mRNAs for the intracellular metabolism of FAs, such as long chain acyl-CoA synthetase, carnitine palmitoyltransferase (CPT)-1a and -1c and uncoupling protein-2 (UCP2) [24].”
BackgroundInfluentialSelf-citationPhysiologic and Neural Controls of Eating
Moran, T. H., & Ladenheim, E. E. (2016) · Gastroenterology Clinics of North America · doi:10.1016/j.gtc.2016.07.009 · Cited by 22
Luo, H., Liang, X., Li, J., Zhang, Y., Xiao, Q., Peng, B., & Zhang, Z. (2019) · Comparative Biochemistry and Physiology Part B Biochemistry and Molecular Biology · doi:10.1016/j.cbpb.2019.110395 · Cited by 20
Fosch, A., Rodriguez-Garcia, M., Miralpeix, C., Zagmutt, S., Larrañaga, M., Reguera, A. C., García-Chica, J., Herrero, L., Serra, D., Casals, N., et al. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24021697 · Cited by 19
“These oleic acid effects are closely related to intracellular accumulation of LCFA-CoA [11,12] and activation of”
BackgroundInfluentialVelasco, C., Librán-Pérez, M., Otero-Rodiño, C., López‐Patiño, M. A., Míguez, J. M., & Soengas, J. L. (2016) · General and Comparative Endocrinology · doi:10.1016/j.ygcen.2016.01.016 · Cited by 18
Routh, V. H., Donovan, C. M., & Ritter, S. (2012) · Translational endocrinology & metabolism · doi:10.1210/team.9781936704200.ch2 · Cited by 19
Triglyceride sensing in the reward circuitry: A new insight in feeding behaviour regulation
Cansell, C., & Luquet, S. H. (2015) · Biochimie · doi:10.1016/j.biochi.2015.07.004 · Cited by 21
Librán-Pérez, M., Otero-Rodiño, C., López‐Patiño, M. A., Míguez, J. M., & Soengas, J. L. (2014) · Aquaculture Nutrition · doi:10.1111/anu.12158 · Cited by 18
Control of metabolism by nutrient-regulated nuclear receptors acting in the brain
Bantubungi, K., Prawitt, J., & Staels, B. (2011) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/j.jsbmb.2011.10.002 · Cited by 19
“Several studies have shown that central administration of oleic acid reduces food intake, body weight, energy homeostasis and hepatic glucose production [81,94-98].”
Solakivi, T., Kunnas, T. A., & Nikkari, S. T. (2015) · Scandinavian Journal of Clinical and Laboratory Investigation · doi:10.3109/00365513.2014.1003596 · Cited by 18
“Since CD36 is a high affi nity, low capacity fatty acid transporter [17], it is thought to be especially suitable to function in cooperation with other receptors in fatty acid sensing [18,19].”
BackgroundLong Chain Fatty Acids Differentially Regulate Sub-populations of Arcuate POMC and NPY Neurons
Michael, N. J., & Watt, M. J. (2020) · Neuroscience · doi:10.1016/j.neuroscience.2020.09.045 · Cited by 16
Marsollier, N., Kassis, N., Mezghenna, K., Soty, M., Fioramonti, X., Lacombe, A., Joly‐Amado, A., Pillot, B., Zitoun, C., Vilar, J., et al. (2009) · PLoS ONE · doi:10.1371/journal.pone.0006649 · Cited by 16
“Indeed, growing evidences show involvement of both glucose [5–7] and fatty acids (FA) [8,9] sensitive neurons within hypothalamus, especially arcuate and ventromedial part, in the regulation of both energy homeostasis and food intake [10– 12].”
BackgroundSelf-citationObeticholic acid inhibits hepatic fatty acid uptake independent of FXR in mouse
Lin, C., Yu, B., Liu, X., Chen, L., Zhang, Z., Ye, W., Zhong, H., Bai, W., Yang, Y., & Nie, B. (2022) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2022.112984 · Cited by 15
Fanalli, S. L., da Silva, B. P. M., Gomes, J. D., Durval, M. C., de Almeida, V. V., Moreira, G. C. M., Silva‐Vignato, B., Afonso, J., Freitas, F. A. O., Reecy, J. M., et al. (2023) · Frontiers in Genetics · doi:10.3389/fgene.2023.1053021 · Cited by 15
Dearden, L., Furigo, I. C., Pantaleão, L. C., Wong, L. W. P., Fernandez‐Twinn, D. S., de Almeida-Faria, J., Kentistou, K. A., Carreira, M. V., Bidault, G., Vidal‐Puig, A., et al. (2024) · PLoS Biology · doi:10.1371/journal.pbio.3002641 · Cited by 18
Does Nutrient Sensing Determine How We “See” Food?
Hamr, S. C., Wang, B., Swartz, T. D., & Duca, F. A. (2015) · Current Diabetes Reports · doi:10.1007/s11892-015-0604-7 · Cited by 15
Hypothalamic integration of nutrient sensing in fish
Soengas, J. L., Comesaña, S., Conde‐Sieira, M., & Blanco, A. M. (2024) · Journal of Experimental Biology · doi:10.1242/jeb.247410 · Cited by 14
Otero-Rodiño, C., Velasco, C., Álvarez‐Otero, R., López‐Patiño, M. A., Míguez, J. M., & Soengas, J. L. (2016) · Journal of Experimental Biology · doi:10.1242/jeb.137737 · Cited by 13
“The concentrations of inhibitors/antagonists was selected based on previous studies in fish (Soengas and Moon, 1998; Librán-Pérez et al., 2013) and mammals (Forman et al., 1997; Le Foll et al., 2009; Maillet et al., 2009).”
MethodDadak, S., Beall, C., Walker, J. M. V., Soutar, M. P. M., McCrimmon, R. J., & Ashford, M. L. J. (2017) · Neuroscience · doi:10.1016/j.neuroscience.2016.12.053 · Cited by 14
“The concentration of oleate used here is larger than that previously used in some studies of hypothalamic glucose-sensing neurons (Wang et al., 2006; Le Foll et al., 2009), although a recent study in humans measured an oleate level of >10 lM in the CSF of nonobese humans (Levi et al., 2013).”
BackgroundMethodResultInfluentialOnaolapo, A. Y., Ojo, F. O., Adeleye, O. O., Falade, J., & Onaolapo, O. J. (2023) · Current Diabetes Reviews · doi:10.2174/1573399819666230102141154 · Cited by 14
Yılmaz, B., Erdogan, C. S., Sandal, S., Keleştimur, F., & Carpenter, D. O. (2024) · Neuroendocrinology · doi:10.1159/000542901 · Cited by 13
“Specialized neurons in the ventromedial nucleus and ARC can detect changes in FA levels [90, 91] via multiple pathways for FA sensing, including intracellular metabolism and interaction with the FA transporter/receptor FAT/CD36, and can be either inhibited or activated by FAs [92, 93].”
Otero-Rodiño, C., Velasco, C., Álvarez‐Otero, R., López‐Patiño, M. A., Míguez, J. M., & Soengas, J. L. (2016) · Comparative Biochemistry and Physiology Part B Biochemistry and Molecular Biology · doi:10.1016/j.cbpb.2016.04.010 · Cited by 12
Cell mechanisms of gustatory lipids perception and modulation of the dietary fat preference
Dramane, G., Akpona, S., Besnard, P., & Khan, N. A. (2014) · Biochimie · doi:10.1016/j.biochi.2014.06.018 · Cited by 12
Rebello, C. J., O’Neil, C. E., & Greenway, F. (2015) · International Journal of Obesity · doi:10.1038/ijo.2015.142 · Cited by 12
Circulating free fatty acids inhibit food intake in an oleate-specific manner in rats
Oh, Y. T., Oh, H. H., Nguyen, A.-K., Choi, C. S., & Youn, J. H. (2016) · Physiology & Behavior · doi:10.1016/j.physbeh.2016.09.015 · Cited by 12
Outcomes associated with timing of maintenance treatment for COPD exacerbation.
Dalal, A. A., Shah, M. B., D’Souza, A. O., Dhamane, A. D., & Crater, G. (2012) · PubMed · Cited by 10
Brain lipid sensing and the neural control of energy balance
Cruciani‐Guglielmacci, C., Stunff, H. L., & Magnan, C. (2024) · Biochimie · doi:10.1016/j.biochi.2024.05.020 · Cited by 13
Self-citationFat sensing and metabolic syndrome
Youn, J. H. (2014) · Reviews in Endocrine and Metabolic Disorders · doi:10.1007/s11154-014-9300-1 · Cited by 10
CD36 Deficiency Suppresses Epileptic Seizures
Zheng, F., Yang, Y., Lu, S., Yang, Q. Z., Li, Y., Xu, X., Zhang, Y., Liu, F., Tian, X., & Wang, X. (2017) · Neuroscience · doi:10.1016/j.neuroscience.2017.10.024 · Cited by 10
Lipid-Induced Peroxidation in the Intestine Is Involved in Glucose Homeostasis Imbalance in Mice
Sérino, M., Waget, A., Marsollier, N., Masseboeuf, M., Payros, G., Gallou‐Kabani, C., Denom, J., Lacombe, A., Thiers, J., Nègre‐Salvayre, A., et al. (2011) · PLoS ONE · doi:10.1371/journal.pone.0021184 · Cited by 10
“Among nutrients, increasing evidence suggests an important role for an intestinal lipid-induced gutbrain neuronal axis to regulate energy homeostasis [9,10] as well as direct hypothalamic fatty acid (FA) sensing [11,12,13].”
BackgroundSelf-citation
Metadata
- Authors
- Le Foll, C., Irani, B. G., Magnan, C., Dunn-Meynell, A. A., & Levin, B. E.
- ORCID
- Levin, Barry E.
- Venue
- American Journal of Physiology-Regulatory, Integrative and Comparative Physiology
- Publisher
- American Physiological Society
- Published
- 2009-09
- Volume
- 297
- Issue
- 3
- Pages
- R655-R664
- ISSN
- 0363-6119 (ISSN-L)
- 1522-1490
- PMC
- PMC2739790
- OpenAlex
- W2067285665
- Cited by
- 159
- References
- 57
- Citations by year
- 2026: 4 · 2025: 5 · 2024: 7 · 2023: 7 · 2022: 4 · 2021: 7 · 2020: 6 · 2019: 6 · 2018: 3 · 2017: 15 · 2016: 13 · 2015: 15 · 2014: 18 · 2013: 17 · 2012: 9
- FWCI
- 4.79
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- American Journal of Physiology-Regulatory, Integrative and Comparative Physiology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Diabetes and Digestive and Kidney Diseases (DK 53181, R01DK053181)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Neuroscience of respiration and sleep
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
- Keywords
- ventromedial hypothalamus, oleic acid, fatty acid sensing, glucose detection, energy homeostasis, neuronal excitation and inhibition, CD36, fatty acid transporters, carnitine palmitoyltransferase, reactive oxygen species, ATP-sensitive potassium channels, UCP2, fasting and feeding
- MeSH terms
- Uncoupling Protein 2, Animals, Carnitine O-Palmitoyltransferase, Coenzyme A Ligases, Energy Metabolism, Enzyme Inhibitors, Glucose, Homeostasis, Ion Channels, Male, Membrane Potentials, Microscopy, Fluorescence, Neural Inhibition, Neurons, Time Factors, Ventromedial Hypothalamic Nucleus, Free Radical Scavengers, Rats, Sprague-Dawley, Reactive Oxygen Species, CD36 Antigens, Oleic Acid, Calcium Signaling, Mitochondrial Proteins, Potassium Channel Blockers, Rats, KATP Channels
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
