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.
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Basal levels of fatty acid oxidation enzymes and fatty acid transport proteins (such as FATP-1, FATP-4, and FAT/CD36) are expressed in hypothalamic neurons.
“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]
Hypothalamic neurons have the capacity to sense glucose and free fatty acids simultaneously and to integrate other nutritional and hormonal inputs.
“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]
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“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 · see citing works
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 · see citing works
“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 69 · see citing works
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 63 · see citing works
“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 · see citing works
“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 · see citing works
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 56 · see citing works
“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 57 · see citing works
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 54 · see citing works
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 · see citing works
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 54 · see citing works
“…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 50 · see citing works
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 48 · see citing works
“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. H., & Cruciani‐Guglielmacci, C. (2012) · Frontiers in Physiology · doi:10.3389/fphys.2012.00385 · Cited by 48 · see citing works
“…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 · see citing works
“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 45 · see citing works
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 44 · see citing works
“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 44 · see citing works
“…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 43 · see citing works
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 · see citing works
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 41 · see citing works
“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 39 · see citing works
“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., & Lopaschuk, G. (2013) · Physiology and Behavior · doi:10.1016/j.physbeh.2013.03.030 · Cited by 43 · see citing works
“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 · see citing works
“…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 · see citing works
“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 35 · see citing works
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 34 · see citing works
“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. F., 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 34 · see citing works
“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 34 · see citing works
Otlivanchik, O., Foll, C. L., & Levin, B. E. (2014) · Diabetes · doi:10.2337/db14-0671 · Cited by 32 · see citing works
“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 30 · see citing works
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 33 · see citing works
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 30 · see citing works
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 · see citing works
Self-citationLaperrousaz, E., Moullé, V. S. F., 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 · see citing works
“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 29 · see citing works
“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 · see citing works
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 · see citing works
Hypothalamic Nutrient Sensing and Energy Balance
Moran, T. H. (2009) · Forum of nutrition/Bibliotheca Nutritio et dieta · doi:10.1159/000264397 · Cited by 27 · see citing works
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 26 · see citing works
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 · see citing works
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 24 · see citing works
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 · see citing works
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 21 · see citing works
Stunff, H. L., Coant, N., Migrenne, S., & Magnan, C. (2013) · Expert Opinion on Therapeutic Targets · doi:10.1517/14728222.2013.768233 · Cited by 21 · see citing works
“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 21 · see citing works
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 · see citing works
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 18 · see citing works
“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 19 · see citing works
Routh, V. H., Donovan, C. M., & Ritter, S. (2012) · Translational endocrinology & metabolism · doi:10.1210/team.9781936704200.ch2 · Cited by 19 · see citing works
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 18 · see citing works
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 · see citing works
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 18 · see citing works
“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 · see citing works
“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 · see citing works
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 · see citing works
“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 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
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 13 · see citing works
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 · see citing works
“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 12 · see citing works
“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 · see citing works
Yılmaz, B., Erdogan, C. S., Sandal, S., Keleştimur, F., & Carpenter, D. O. (2024) · Neuroendocrinology · doi:10.1159/000542901 · Cited by 12 · see citing works
“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 · see citing works
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 · see citing works
Rebello, C. J., O’Neil, C. E., & Greenway, F. (2015) · International Journal of Obesity · doi:10.1038/ijo.2015.142 · Cited by 12 · see citing works
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 · see citing works
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 · see citing works
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 12 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
“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
- 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 ›
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