Astrocytic GABA in LHA is an obesity ‘thermostat’

Neuroscience

Nature Metabolism (2023)Cite this article

10 Altmetric

Metrics details

Sa et al. identified a distinct neuronal subpopulation that controls brown adipose tissue thermogenesis. In mice fed a high-fat diet, hypothalamic GABRA5 neurons are deactivated by GABA released by surrounding astrocytes and inhibition of GABA synthesis ameliorates diet-induced obesity.

In mammals, the hypothalamus acts as the body’s ‘thermostat’ for temperature and weight regulation. Within the hypothalamus, the lateral hypothalamic area (LHA) stands out for its distinct role in controlling hunger1,2,3. Additionally, specific neuronal populations in the LHA that innervate brown adipose tissue are known to influence thermogenic activity and energy balance4,5. Despite extensive research aimed at unravelling these complex thermoregulatory circuits, a previously unnoticed neuronal population within the LHA has now come to the forefront.

This is a preview of subscription content, access via your institution

Access Nature and 54 other Nature Portfolio journals

Get Nature+, our best-value online-access subscription

$29.99 / 30 days

cancel any time

Subscribe to this journal

Receive 12 digital issues and online access to articles

$119.00 per year

only $9.92 per issue

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

Prices may be subject to local taxes which are calculated during checkout

Berthoud, H. R. & Münzberg, H. Physiol. Behav. 104, 29–39 (2011).

Article CAS PubMed PubMed Central Google Scholar

Jennings, J. H., Rizzi, G., Stamatakis, A. M., Ung, R. L. & Stuber, G. D. Science 341, 1517–1521 (2013).

Article CAS PubMed PubMed Central Google Scholar

Jennings, J. H. et al. Cell 160, 516–527 (2015).

Article CAS PubMed PubMed Central Google Scholar

Cerri, M. & Morrison, S. F. Neuroscience 135, 627–638 (2005).

Article CAS PubMed Google Scholar

Folgueira, C. et al. Nat. Metab. 1, 811–829 (2019).

Article CAS PubMed PubMed Central Google Scholar

Sa, M. et al. Nat. Metab. https://doi.org/10.1038/s42255-023-008XX-x (2023).

Article Google Scholar

Denroche, H. C. et al. Endocrinology 157, 2671–2685 (2016).

Article CAS PubMed Google Scholar

Rossi, M. A. et al. Science 364, 1271–1274 (2019).

Article CAS PubMed PubMed Central Google Scholar

Buckman, L. B., Thompson, M. M., Moreno, H. N. & Ellacott, K. L. J. Comp. Neurol. 521, 1322–1333 (2013).

Article CAS PubMed PubMed Central Google Scholar

Escartin, C. et al. Nat. Neurosci. 24, 312–325 (2021).

Article CAS PubMed PubMed Central Google Scholar

Thaler, J. P. et al. J. Clin. Invest. 122, 153–162 (2012).

Article CAS PubMed Google Scholar

Gruber, T. et al. Cell Metab. 33, 1155–1170.e10 (2021).

Article CAS PubMed PubMed Central Google Scholar

Lutomska, L. M. et al. Glia 70, 2062–2078 (2022).

Article CAS PubMed Google Scholar

González-García, I. & García-Cáceres, C. Int. J. Mol. Sci. 22, 6176 (2021).

Article PubMed PubMed Central Google Scholar

Download references

We thank C. Holleman (Helmholtz Munich; Germany) for her comments. The research of the authors is supported by funding from the European Research Council (ERC) (C.G.-C.: STG grant AstroNeuroCrosstalk no. 757393), the German Research Foundation (DFG) under Germany’s Excellence Strategy within the framework of the Munich Cluster for Systems Neurology (EXC 2145 SyNergy – ID 390857198), and Helmholtz Association - Initiative and Networking Fund. I.G.-G. is supported by a Ramón y Cajal Award (RYC2021-031225-I) from the Ministerio de Ciencia e Innovación of Spain. The funders had no role in decision to publish or prepare this work.

Department of Physiology, CiMUS, University of Santiago de Compostela–Instituto de Investigación Sanitaria, Santiago de Compostela, Spain

Ismael González-García

CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Santiago de Compostela, Spain

Ismael González-García

Institute for Diabetes and Obesity, Helmholtz Diabetes Center, Helmholtz Munich & German Center for Diabetes Research (DZD), Neuherberg, Germany

Cristina García-Cáceres

Medizinische Klinik und Poliklinik IV, Klinikum der Universität, Ludwig Maximilians Universität München, Munich, Germany

Cristina García-Cáceres

You can also search for this author in PubMed Google Scholar

You can also search for this author in PubMed Google Scholar

Correspondence to Ismael González-García or Cristina García-Cáceres.

The authors declare no competing interests.

Reprints and Permissions

González-García, I., García-Cáceres, C. Astrocytic GABA in LHA is an obesity ‘thermostat’. Nat Metab (2023). https://doi.org/10.1038/s42255-023-00849-0

Download citation

Published: 31 August 2023

DOI: https://doi.org/10.1038/s42255-023-00849-0

Anyone you share the following link with will be able to read this content:

Sorry, a shareable link is not currently available for this article.

Provided by the Springer Nature SharedIt content-sharing initiative