GABAergic RIP-Cre Neurons in the Arcuate Nucleus Selectively Regulate Energy Expenditure
Open accessAbstract
Neural regulation of energy expenditure is incompletely understood. By genetically disrupting GABAergic transmission in a cell-specific fashion, and by combining this with selective pharmacogenetic activation and optogenetic mapping techniques, we have uncovered an arcuate-based circuit that selectively drives energy expenditure. Specifically, mice lacking synaptic GABA release from RIP-Cre neurons have reduced energy expenditure, become obese and are extremely sensitive to high-fat diet-induced obesity, the latter due to defective diet-induced thermogenesis. Leptin's ability to stimulate thermogenesis, but not to reduce feeding, is markedly attenuated. Acute, selective activation of arcuate GABAergic RIP-Cre neurons, which monosynaptically innervate PVH neurons projecting to the NTS, rapidly stimulates brown fat and increases energy expenditure but does not affect feeding. Importantly, this response is dependent upon GABA release from RIP-Cre neurons. Thus, GABAergic RIP-Cre neurons in the arcuate selectively drive energy expenditure, contribute to leptin's stimulatory effect on thermogenesis, and protect against diet-induced obesity.
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AGRP neurons have been associated with the negative regulation of energy expenditure.
“AGRP neurons have also been associated with the negative regulation of energy expenditure36–38.”
From IDOL regulates systemic energy balance through control of neuronal VLDLR expression (2019) · cites this paper as [37]
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- Authors
- Kong, D., Tong, Q., Ye, C., Koda, S., Fuller, P. M., Krashes, M. J., Vong, L., Ray, R. S., Olson, D. P., & Lowell, B. B.
- Affiliations
- Beth Israel Deaconess Medical Center (US)
- Harvard University (US)
- Corresponding author
- Lowell, Bradford B.
- ORCID
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2012-10
- Volume
- 151
- Issue
- 3
- Pages
- 645-657
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC3500616
- OpenAlex
- W2021519886
- Cited by
- 215
- References
- 13
- Citations by year
- 2026: 6 · 2025: 10 · 2024: 9 · 2023: 9 · 2022: 9 · 2021: 9 · 2020: 17 · 2019: 7 · 2018: 16 · 2017: 29 · 2016: 21 · 2015: 23 · 2014: 30 · 2013: 17 · 2012: 2
- FWCI
- 9.71
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Diabetes and Digestive and Kidney Diseases (P30DK057521, R01DK075632, R01DK089044, R01DK071051, P30DK046200, K08DK071561, P30DK0460200, R01DK096010, R37DK053477, R01DK092605, P30DK020572)
- National Institute of Neurological Disorders and Stroke (NS0736313, R01NS073613)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
- Keywords
- GABAergic neurons, arcuate nucleus, energy expenditure, leptin, diet-induced obesity, high-fat diet, thermogenesis, brown adipose tissue, paraventricular nucleus, nucleus tractus solitarius, food intake regulation, optogenetic stimulation
- MeSH terms
- Animals, Arcuate Nucleus of Hypothalamus, Adipose Tissue, Brown, Diet, Energy Metabolism, Neural Pathways, Obesity, Paraventricular Hypothalamic Nucleus, Integrases, Leptin, Vesicular Inhibitory Amino Acid Transport Proteins, Vesicular Glutamate Transport Protein 2, Mice, GABAergic Neurons
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