| Title |
Dietary sugars, not lipids, drive hypothalamic inflammation
|
|---|---|
| Published in |
Molecular Metabolism, June 2017
|
| DOI | 10.1016/j.molmet.2017.06.008 |
| Pubmed ID | |
| Authors |
Yuanqing Gao, Maximilian Bielohuby, Thomas Fleming, Gernot F. Grabner, Ewout Foppen, Wagner Bernhard, Mara Guzmán-Ruiz, Clarita Layritz, Beata Legutko, Erwin Zinser, Cristina García-Cáceres, Ruud M. Buijs, Stephen C. Woods, Andries Kalsbeek, Randy J. Seeley, Peter P. Nawroth, Martin Bidlingmaier, Matthias H. Tschöp, Chun-Xia Yi |
| Abstract |
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. 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). 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. Combined overconsumption of fat and sugar, but not the overconsumption of fat per se, 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. |
X Demographics
The data shown below were collected from the profiles of 489 X users who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United States | 93 | 19% |
| United Kingdom | 22 | 4% |
| Canada | 19 | 4% |
| Spain | 18 | 4% |
| Mexico | 10 | 2% |
| Australia | 9 | 2% |
| Brazil | 8 | 2% |
| India | 8 | 2% |
| Netherlands | 7 | 1% |
| Other | 54 | 11% |
| Unknown | 241 | 49% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 406 | 83% |
| Practitioners (doctors, other healthcare professionals) | 52 | 11% |
| Scientists | 22 | 4% |
| Science communicators (journalists, bloggers, editors) | 9 | 2% |
Mendeley readers
The data shown below were compiled from readership statistics for 220 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 220 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Researcher | 40 | 18% |
| Student > Ph. D. Student | 35 | 16% |
| Student > Master | 29 | 13% |
| Student > Bachelor | 22 | 10% |
| Other | 12 | 5% |
| Other | 37 | 17% |
| Unknown | 45 | 20% |
| Readers by discipline | Count | As % |
|---|---|---|
| Biochemistry, Genetics and Molecular Biology | 37 | 17% |
| Neuroscience | 35 | 16% |
| Medicine and Dentistry | 34 | 15% |
| Agricultural and Biological Sciences | 21 | 10% |
| Nursing and Health Professions | 11 | 5% |
| Other | 24 | 11% |
| Unknown | 58 | 26% |
Attention Score in Context
This research output has an Altmetric Attention Score of 321. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 15 January 2024.
All research outputs
#106,887
of 25,726,194 outputs
Outputs from Molecular Metabolism
#11
of 1,630 outputs
Outputs of similar age
#2,356
of 330,986 outputs
Outputs of similar age from Molecular Metabolism
#1
of 47 outputs
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