Leptin and insulin pathways in POMC and AgRP neurons that modulate energy balance and glucose homeostasis.
Open accessAbstract
With the steady rise in the prevalence of obesity and its associated diseases, research aimed at understanding the mechanisms that regulate and control whole body energy homeostasis has gained new interest. Leptin and insulin, two anorectic hormones, have key roles in the regulation of body weight and energy homeostasis, as highlighted by the fact that several obese patients develop resistance to these hormones. Within the brain, the hypothalamic proopiomelanocortin and agouti-related protein neurons have been identified as major targets of leptin and insulin action. Many studies have attempted to discern the individual contributions of various components of the principal pathways that mediate the central effects of leptin and insulin. The aim of this review is to discuss the latest findings that might shed light on, and lead to a better understanding of, energy balance and glucose homeostasis. In addition, recently discovered targets and mechanisms that mediate hormonal action in the brain are highlighted.
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Energy expenditure in mice is predominantly regulated by the hypothalamus, centrally, and largely by thermogenic brown adipose tissue (BAT), peripherally.
“Energy expenditure in mice is predominantly regulated by the hypothalamus, centrally, and largely by thermogenic brown adipose tissue (BAT), peripherally (Varela and Horvath, 2012; Harms and Seale, 2013; Schneeberger et al., 2014).”
From Deletion of the Alzheimer’s disease risk gene Abi3 locus results in obesity and systemic metabolic disruption in mice (2022) · cites this paper as Varela and Horvath, 2012
The Introduction (page unavailable) describes the hypothalamus as pivotal in regulating energy homeostasis, supporting the central-regulation part of the claim. It does not establish that the hypothalamus predominantly regulates energy expenditure in mice or that thermogenic brown adipose tissue accounts for much of its peripheral regulation; searches for brown adipose tissue and thermogenesis found no supporting passage. (LLM, conf=0.83)
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Haynes, V. R., Michael, N., van den Top, M., Zhao, F.-Y., Brown, R. D., de Souza, D. D., Dodd, G., Spanswick, D., & Watt, M. (2020) · Molecular Metabolism · doi:10.1016/j.molmet.2020.01.002 · Cited by 39 · see citing works
Weiner, J., Zieger, K., Pippel, J., & Heiker, J. T. (2018) · Advances in experimental medicine and biology · doi:10.1007/5584_2018_241 · Cited by 49 · see citing works
- Authors
- Varela, L., & Horvath, T. L.
- Affiliations
- Yale University (US)
- ORCID
- Varela, Luis
- Venue
- The EMBO Reports
- Published
- 2012-11-13
- Volume
- 13
- Issue
- 12
- Pages
- 1079-1086
- ISSN
- 1469-221X (ISSN-L)
- 1469-3178
- PMC
- PMC3512417
- OpenAlex
- W2111734250
- Cited by
- 426
- References
- 80
- Citations by year
- 2026: 19 · 2025: 30 · 2024: 25 · 2023: 21 · 2022: 45 · 2021: 49 · 2020: 41 · 2019: 31 · 2018: 33 · 2017: 38 · 2016: 28 · 2015: 26 · 2014: 26 · 2013: 14
- FWCI
- 2.38
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- EMBO Reports (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Diabetes and Digestive and Kidney Diseases (DP1DK098058)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Keywords
- leptin, insulin, POMC neurons, AgRP neurons, hypothalamus, energy homeostasis, glucose homeostasis, obesity, leptin resistance, insulin resistance
- MeSH terms
- Insulin Secretion, Adipose Tissue, Brain, Energy Metabolism, Glucose, Homeostasis, Humans, Insulin, Obesity, Signal Transduction, Leptin, Proprotein Convertases, Agouti-Related Protein
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