Dataset Information

Dietary sugars, not lipids, drive hypothalamic inflammation.

ABSTRACT:

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(?)-(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

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.

SUBMITTER: Gao Y

PROVIDER: S-EPMC5518723 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature

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Publications

Dietary sugars, not lipids, drive hypothalamic inflammation.

Gao Yuanqing Y Bielohuby Maximilian M Fleming Thomas T Grabner Gernot F GF Foppen Ewout E Bernhard Wagner W Guzmán-Ruiz Mara M Layritz Clarita C Legutko Beata B Zinser Erwin E García-Cáceres Cristina C Buijs Ruud M RM Woods Stephen C SC Kalsbeek Andries A Seeley Randy J RJ Nawroth Peter P PP Bidlingmaier Martin M Tschöp Matthias H MH Yi Chun-Xia CX

Molecular metabolism 20170620 8

<h4>Objective</h4>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.<h4>Methods</h4>We dissected the different effects of high-carbohydrate high-fat (HCHF) diets and ...[more]

PMID: 28752053

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Project description:BACKGROUND AND AIMS:The objective of this study was to assess the feasibility (ability to recruit participants and develop the 12-month intervention), acceptability (retention of participants in the intervention), and impact on systemic inflammation and Dietary Inflammatory Index (DII®) scores over a 12-month DII-based intervention. METHODS:Adults were recruited to participate in a self-selection trial (intervention: n = 61, in-person classes; control: n = 34, newsletters). Classes included participatory cooking and dietary recommendations focused on consuming a plant-based diet rich in anti-inflammatory foods (spices, vegetables, etc.). Changes in markers of inflammation, lipids, and DII were analyzed using general linear models with repeated measurements. RESULTS:At 3 months, intervention participants had significantly lower DII scores (-2.66 ± 2.44) compared to controls (-0.38 ± 2.56) (p < 0.01); but not at 12 months (P = 0.10). The only biomarker to approach a significant group effect or group-by-time interaction was CRP (P = 0.11 for the group-by-time interaction). CRP decreased by -0.65 mg/L (95%CI = 0.10-1.20, P = 0.02) at 12 months in the intervention group; no significant decrease was seen for the control group. With both groups combined at 3 months, those with the greatest decrease/improvement in DII score (tertile 1) compared with those whose scores increased (tertile 3) had greater reductions in CRP (-1.09 vs. +0.52 mg/L, P = 0.04), total cholesterol (-9.38 vs. +12.02 mg/dL, P = 0.01), and LDL cholesterol (-11.99 vs. +7.16 mg/dL, P = 0.01). CONCLUSIONS:Although the intervention group had reductions in DII and CRP, main inflammation and lipid outcomes did not differ between groups. Overall, those participants with the largest reduction in DII scores had the largest reductions in CRP and LDL and total cholesterol. Future interventions may need to have more components in place to support maintenance and continued reductions in the DII. CLINICALTRIALS. GOV IDENTIFIER:NCT02382458.

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Dataset Information

Dietary sugars, not lipids, drive hypothalamic inflammation.

Objective

Methods

Results

Conclusions

Publications

Dietary sugars, not lipids, drive hypothalamic inflammation.

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