The DOI matches its Crossref record; 67 of the 67 references it cites were found in a registry or an index.
Hypothalamic inflammation and energy homeostasis: Resolving the paradox
Abstract
Determining the effect of hypothalamic inflammatory signals on energy balance presents a paradox. On the one hand, a large body of work has identified inflammatory signaling in the hypothalamus as an essential mediator of the sickness response--the anorexia, cachexia, fever, inactivity, lethargy, anhedonia and adipsia that are triggered by systemic inflammatory stimuli and promote negative energy balance. On the other hand, numerous recent studies implicate inflammatory activation within the hypothalamus as a key factor whereby high-fat diets--and saturated fats in particular--cause central leptin and insulin resistance and thereby promote the defense of elevated body weight. This paradox will likely remain unresolved until several issues have been addressed. Firstly, the hypothalamus--unlike many peripheral inflamed tissues--is an extremely heterogeneous tissue comprised of astrocytes, oligodendrocytes, microglia, endothelial cells, ependymal cells as well as numerous neuronal subgroups. Determining exactly which cells activate defined inflammatory signals in response to a particular stimulus--i.e. sepsis vs. nutrient excess--may yield critical clues. Secondly, for the sake of simplicity many studies evaluate inflammation as an on/off phenomenon. More realistically, inflammatory signaling occurs as a cascade or cycle that changes and progresses over time. Accordingly, even within the same cell type, the low-grade, chronic signal induced by nutrient excess may invoke a different cascade of signals than a strong, acute signal such as sepsis. In addition, because tolerance can develop to certain inflammatory mediators, physiological outcomes may not correlate with early biochemical markers. Lastly, the neuroanatomical location, magnitude, and duration of the inflammatory stimulus can undoubtedly influence the net CNS response. Rigorously evaluating the progression of the inflammatory signaling cascade within specific hypothalamic cell types is a key next step towards resolving the paradox surrounding the effect of inflammatory signaling on energy homeostasis.
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“A number of recent studies directed attention to the hypothalamus, where high-fat diets disturb the delicate relationship between glial cells and neurons through increased endoplasmic reticulum and oxidative stress, leading to stress-response pathways with generally cytotoxic effects ([48](#B48), [121](#B121), [177](#B177), [198](#B198)).”
From Food reward, hyperphagia, and obesity (2011) · cites this paper as [177]
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Metadata
- Authors
- Thaler, J. P., Choi, S. J., Schwartz, M. W., & Wisse, B. E.
- Affiliations
- University of Washington (US)
- Yonsei University (KR)
- Corresponding author
- Wisse, Brent E.
- Venue
- Frontiers in Neuroendocrinology
- Publisher
- Elsevier BV
- Published
- 2010-01
- Volume
- 31
- Issue
- 1
- Pages
- 79-84
- ISSN
- 0091-3022 (ISSN-L)
- OpenAlex
- W2005519734
- Cited by
- 144
- References
- 67
- Citations by year
- 2026: 4 · 2025: 5 · 2024: 2 · 2023: 8 · 2022: 4 · 2021: 5 · 2020: 6 · 2019: 5 · 2018: 4 · 2017: 11 · 2016: 7 · 2015: 12 · 2014: 15 · 2013: 13 · 2012: 18
- FWCI
- 1.58
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Frontiers in Neuroendocrinology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK074758)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- hypothalamic inflammation, energy homeostasis, anorexia, cachexia, leptin resistance, insulin resistance, high-fat diet, saturated fat, microglia, astrocytes, sepsis, low-grade inflammation, neuroinflammation
- MeSH terms
- Animals, Dietary Fats, Eating, Energy Metabolism, Homeostasis, Humans, Hypothalamus, Inflammation, Insulin Resistance, Obesity, Signal Transduction, Weight Gain, Leptin, Melanocortins
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