The DOI matches its Crossref record; 42 of the 42 references it cites were found in a registry or an index.
Dietary sugars, not lipids, drive hypothalamic inflammation
Open accessAbstract
OBJECTIVE: The hypothalamus of hypercaloric diet-induced obese animals is featured by a significant increase of microglial reactivity and its associated cytokine production. However, the role of dietary components, in particular fat and carbohydrate, with respect to the hypothalamic inflammatory response and the consequent impact on hypothalamic control of energy homeostasis is yet not clear. METHODS: We dissected the different effects of high-carbohydrate high-fat (HCHF) diets and low-carbohydrate high-fat (LCHF) diets on hypothalamic inflammatory responses in neurons and non-neuronal cells and tested the hypothesis that HCHF diets induce hypothalamic inflammation via advanced glycation end-products (AGEs) using mice lacking advanced glycation end-products (AGEs) receptor (RAGE) and/or the activated leukocyte cell-adhesion molecule (ALCAM). RESULTS: We found that consumption of HCHF diets, but not of LCHF diets, increases microgliosis as well as the presence of N(ε)-(Carboxymethyl)-Lysine (CML), a major AGE, in POMC and NPY neurons of the arcuate nucleus. Neuron-secreted CML binds to both RAGE and ALCAM, which are expressed on endothelial cells, microglia, and pericytes. On a HCHF diet, mice lacking the RAGE and ALCAM genes displayed less microglial reactivity and less neovasculature formation in the hypothalamic ARC, and this was associated with significant improvements of metabolic disorders induced by the HCHF diet. CONCLUSIONS: , leads to excessive CML production in hypothalamic neurons, which, in turn, stimulates hypothalamic inflammatory responses such as microgliosis and eventually leads to neuronal dysfunction in the control of energy metabolism.
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“The presence of excess sugar in a HFD was shown to be necessary for hypothalamic inflammatory responses in mice, including the activation of microglia, the resident immune cells of the brain [58].”
From The menace of obesity to depression and anxiety prevalence (2022) · cites this paper as [58]
In the citing paper
“Advanced glycation end products (AGEs) are a complex and heterogeneous group of protein, lipid, and DNA adducts implicated in the development of numerous chronic diseases including diabetes related complications, cardiovascular, renal, and neurodegenerative disease, and have recently also been implicated in hypothalamic inflammation and obesity.[1]”
From The Role of Dietary Advanced Glycation End Products in Metabolic Dysfunction (2021) · cites this paper as [1]
In the citing paper
“AGEs are produced both naturally in the body, as part of normal metabolism, and during the cooking and processing of food with a significant proportion being absorbed in the gastrointestinal tract.”
From The Role of Dietary Advanced Glycation End Products in Metabolic Dysfunction (2021) · cites this paper as [1]
In the citing paper
“In mice, where AGEs were identified as being the mechanism by which a high-fat diet causes hypothalamic inflammation, knockdown of both RAGE and AL-CAM was required to block the proinflammatory effects of CML.[1]”
From The Role of Dietary Advanced Glycation End Products in Metabolic Dysfunction (2021) · cites this paper as [1]
In the citing paper
“In support of this, a diet high in both lipids and carbohydrates is required to induce a significant increase in hypothalamic inflammation in rodents associated with an increase in body weight.[1,150]”
From The Role of Dietary Advanced Glycation End Products in Metabolic Dysfunction (2021) · cites this paper as [1]
In the citing paper
“The high-fat and high-carbohydrate diet also caused an increase in CML immunoreactivity in both POMC and NPY neurons.”
From The Role of Dietary Advanced Glycation End Products in Metabolic Dysfunction (2021) · cites this paper as [1]
In the citing paper
“The role of AGEs in promoting hypothalamic inflammation was confirmed in animals lacking RAGE and ALCAM which have an improved metabolic phenotype and decreased microglial reactivity on a high-fat diet.[1]”
From The Role of Dietary Advanced Glycation End Products in Metabolic Dysfunction (2021) · cites this paper as [1]
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“The presence of excess sugar in a HFD was shown to be necessary for hypothalamic inflammatory responses in mice, including the activation of microglia, the resident immune cells of the brain [58].”
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The Role of Dietary Advanced Glycation End Products in Metabolic Dysfunction
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Metadata
- Authors
- Gao, Y., Bielohuby, M., Fleming, T., Grabner, G. F., Foppen, E., Bernhard, W., Guzmán-Ruiz, M., Layritz, C., Legutko, B., Zinser, E., García-Cáceres, C., Buijs, R. M., Woods, S. C., Kalsbeek, A., Seeley, R. J., Nawroth, P. P., Bidlingmaier, M., Tschöp, M. H., & Yi, C.-X.
- Affiliations
- Amsterdam UMC Location University of Amsterdam (NL)
- LMU Klinikum (DE)
- University Hospital Heidelberg (DE)
- University of Graz (AT)
- Helmholtz Munich (DE)
- FH JOANNEUM University of Applied Sciences (AT)
- Universidad Nacional Autónoma de México (MX)
- University of Cincinnati (US)
- Netherlands Institute for Neuroscience (NL)
- University of Michigan (US)
- Corresponding author
- Bidlingmaier, Martin
- Tschöp, Matthias H.
- Yi, Chun-Xia
- ORCID
- Venue
- Molecular Metabolism
- Publisher
- Elsevier BV
- Published
- 2017-08
- Volume
- 6
- Issue
- 8
- Pages
- 897-908
- ISSN
- 2212-8778 (ISSN-L)
- PMC
- PMC5518723
- OpenAlex
- W2652575518
- Cited by
- 131
- References
- 41
- Citations by year
- 2026: 6 · 2025: 10 · 2024: 12 · 2023: 15 · 2022: 18 · 2021: 23 · 2020: 13 · 2019: 22 · 2018: 9 · 2017: 2
- FWCI
- 6.27
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Molecular Metabolism (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Pure Amsterdam UMC (publishedVersion, other-oa)
- KNAW Research Portal (The Royal Netherlands Academy of Arts and Sciences) (publishedVersion, other-oa)
- FH JOANNEUM ePUB (submittedVersion, cc-by-nc-nd)
- PuSH - Publication Server of Helmholtz Zentrum München (submittedVersion, cc-by-nc-nd)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion, other-oa)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Open access LMU (Ludwid Maxmilian's Universitat Munchen) (submittedVersion, cc-by-nc-nd)
- mediaTUM (Technical University of Munich) (submittedVersion)
- Site cant be reached (submittedVersion, cc-by-nc-nd)
- Funders
- Daiichi-Sankyo
- Alexander von Humboldt-Stiftung
- Deutsche Forschungsgemeinschaft (SFB1123, ANR- 15-CE14-0030, SFB1118)
- U.S. Department of Homeland Security
- Novartis
- Novo Nordisk
- Academisch Medisch Centrum
- Helmholtz Association
- European Research Council (695054)
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
- Keywords
- hypothalamic inflammation, dietary sugar, high-fat high-carbohydrate diet, advanced glycation end products, carboxymethyllysine, microglial activation, RAGE, ALCAM, arcuate nucleus, POMC neurons, NPY neurons, neovasculature, energy homeostasis, obesity, hypercaloric diet, endothelial cells, pericytes
- MeSH terms
- Receptor for Advanced Glycation End Products, Dietary Sugars, Animals, Dietary Fats, Gliosis, Hypothalamus, Inflammation, Male, Mice, Inbred C57BL, Glycation End Products, Advanced, Activated-Leukocyte Cell Adhesion Molecule, Mice, Rats
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