AMPK and the neuroendocrine regulation of appetite and energy expenditure
Abstract
This review highlights recent advances in the hormonal control of hypothalamic AMPK activity and the impact on appetite and energy metabolism. AMPK is an intracellular energy sensor that switches off ATP-consuming pathways and switches on ATP-producing pathways such as glucose uptake and fatty acid oxidation. In this regard, it is well positioned to respond to dynamic changes in metabolic state and nutritional over- or under-supply. Within the hypothalamus, AMPK responds to peripheral hormones that convey metabolic information based on increased plasma concentrations. For example, negative energy balance increases plasma ghrelin concentrations, increases hypothalamic AMPK and drives food intake. Conversely, plasma leptin concentrations are secreted in proportion to adipose levels and leptin suppresses hypothalamic AMPK activity and restricts food intake. This review explains that hypothalamic AMPK mediates neuroendocrine feedback control of energy metabolism. A current working model suggests that endocrine feedback influences hypothalamic AMPK via a number of mechanisms designed to shift an organism from negative to neutral energy balance. These mechanisms include (1) ghrelin stimulation of AMPK in NPY/AgRP in the arcuate nucleus (2) ghrelin stimulation of AMPK in the ventromedial hypothalamic nucleus, (3) a novel ghrelin-stimulated AMPK-dependent presynaptic mechanism that sustains AgRP neuron firing via a local synaptic memory system, (4) adiponectin stimulation of hypothal…
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The beneficial role of ghrelin in the central nervous system has been widely discussed, including enhanced cognition.
“Moreover, the beneficial role of ghrelin in the central nervous system has been widely discussed, including enhanced cognition [48, 59–61].”
From Protective PLCG2 variants associate with a delayed onset of Alzheimer’s disease among heterozygous APOE ε4 carriers (2026) · cites this paper as [61]
Cites
AMPK and PPARδ Agonists Are Exercise Mimetics
Narkar, V. A., Downes, M., Yu, R. T., Embler, E., Wang, Y.-X., Banayo, E., Mihaylova, M. M., Nelson, M. C., Zou, Y., Juguilon, H., et al. (2008) · Cell · doi:10.1016/j.cell.2008.06.051 · Cited by 1,222 · see citing works
Abizaid, A., Liu, Z.-W., Andrews, Z. B., Shanabrough, M., Borok, E., Elsworth, J. D., Roth, R. H., Sleeman, M. W., Picciotto, M. R., Tschöp, M. H., et al. (2006) · Journal of Clinical Investigation · doi:10.1172/jci29867 · Cited by 984 · see citing works
Self-citationVousden, K. H., & Ryan, K. M. (2009) · Nature Reviews Cancer · doi:10.1038/nrc2715 · Cited by 959 · see citing works
Adiponectin Stimulates AMP-Activated Protein Kinase in the Hypothalamus and Increases Food Intake
Kubota, N., Yano, W., Kubota, T., Yamauchi, T., Itoh, S., Kumagai, H., Kozono, H., Takamoto, I., Okamoto, S., Shiuchi, T., et al. (2007) · Cell Metabolism · doi:10.1016/j.cmet.2007.06.003 · Cited by 844 · see citing works
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 · see citing works
Self-citationTong, Q., Ye, C., McCrimmon, R. J., Dhillon, H., Choi, B., Kramer, M. D., Yu, J., Yang, Z., Christiansen, L. M., Lee, C. E., et al. (2007) · Cell Metabolism · doi:10.1016/j.cmet.2007.04.001 · Cited by 413 · see citing works
Sixteen years and counting: an update on leptin in energy balance
Gautron, L., & Elmquist, J. K. (2011) · Journal of Clinical Investigation · doi:10.1172/jci45888 · Cited by 367 · see citing works
Leptin-Dependent Control of Glucose Balance and Locomotor Activity by POMC Neurons
Huo, L., Gamber, K., Greeley, S., Silva, J., Huntoon, N., Leng, X.-H., & Bjørbæk, C. (2009) · Cell Metabolism · doi:10.1016/j.cmet.2009.05.003 · Cited by 226 · cited 3× · see citing works
“, 2009), but a strong effect on whole body glucose metabolism (Huo et al., 2009).”
Leptin activates hypothalamic acetyl-CoA carboxylase to inhibit food intake
Gao, S., Kinzig, K. P., Aja, S., Scott, K. A., Keung, W., Kelly, S., Strynadka, K., Chohnan, S., Smith, W. W., Tamashiro, K. L. K., et al. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0708385104 · Cited by 215 · see citing works
Role for insulin signaling in catecholaminergic neurons in control of energy homeostasis
Könner, A. C., Hess, S., Tovar, S., Mesaros, A., Sánchez-Lasheras, C., Evers, N., Verhagen, L. A. W., Brönneke, H. S., Kleinridders, A., Hampel, B., et al. (2011) · Cell Metabolism · doi:10.1016/j.cmet.2011.03.021 · Cited by 194 · see citing works
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AMPK at the Nexus of Energetics and Aging
Burkewitz, K., Zhang, Y., & Mair, W. B. (2014) · Cell Metabolism · doi:10.1016/j.cmet.2014.03.002 · Cited by 483 · see citing works
Metformin: Mechanisms in Human Obesity and Weight Loss
Yerevanian, A., & Soukas, A. A. (2019) · Current Obesity Reports · doi:10.1007/s13679-019-00335-3 · Cited by 414 · see citing works
The physiological control of eating: signals, neurons, and networks
Watts, A. G., Kanoski, S. E., Sanchez-Watts, G., & Langhans, W. (2022) · Physiological Reviews · doi:10.1152/physrev.00028.2020 · Cited by 168 · see citing works
Jeskanen, H., Heikkinen, S., Kervinen, I., Lehtisalo, J., Ngandu, T., Willman, R.-M., Rosa, J., Hoffmann, D., FinnGen, Leinonen, V., et al. (2026) · Alzheimer's Research & Therapy · doi:10.1186/s13195-026-01957-1 · Cited by 1 · see citing works
- Authors
- Stark, R., Ashley, S. E., & Andrews, Z. B.
- Affiliations
- Monash University (AU)
- Corresponding author
- Andrews, Zane B.
- Venue
- Molecular and Cellular Endocrinology
- Publisher
- Elsevier BV
- Published
- 2013-02
- Volume
- 366
- Issue
- 2
- Pages
- 215-223
- ISSN
- 0303-7207 (ISSN-L)
- OpenAlex
- W2129404095
- Cited by
- 94
- References
- 10
- Citations by year
- 2026: 7 · 2025: 5 · 2024: 1 · 2023: 3 · 2022: 8 · 2021: 7 · 2020: 6 · 2019: 6 · 2018: 7 · 2017: 6 · 2016: 9 · 2015: 7 · 2014: 14 · 2013: 7
- FWCI
- 1.03
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Molecular and Cellular Endocrinology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Keywords
- AMPK, hypothalamus, appetite regulation, energy expenditure, energy balance, ghrelin, leptin, adiponectin, arcuate nucleus, NPY/AgRP neurons, ventromedial hypothalamus, synaptic memory, thyroid hormones, neuroendocrine regulation, dietary intake
- MeSH terms
- Appetite, Arcuate Nucleus of Hypothalamus, Eating, Energy Metabolism, Fatty Acids, Glucose, Humans, Neurosecretory Systems, Thyroid Hormones, Ventromedial Hypothalamic Nucleus, Leptin, Feedback, Physiological, Adiponectin, Ghrelin, AMP-Activated Protein Kinases
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