Sustained high‐fat diet modulates inflammation, insulin signalling and cognition in mice and a modified xenin peptide ameliorates neuropathology in a chronic high‐fat model

Denver, Paul; Gault, Victor; McClean, Paula

doi:10.1111/dom.13210

Cited by 55 publications

(50 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This was somewhat of a surprise, since the HF diet was ingested the most of all diets before surgery, and that is consistent with other studies [33,34]. Dietary fat causes low-grade gastrointestinal inflammation in rats [35,36] and in humans [37,38], which is diffused by a layer of visceral fat [39]. It may be speculated that loss of visceral fat shortly after surgery may compromise the endotoxemia barrier, which could then underlie higher sickness behavior after surgery in the HF feeding rats [40].…”

Section: Discussionsupporting

confidence: 86%

Ileal Transposition in Rats Reduces Energy Intake, Body Weight, and Body Fat Most Efficaciously When Ingesting a High-Protein Diet

et al. 2020

View full text Add to dashboard Cite

Purpose Ileal transposition (IT) allows exploration of hindgut effects of bariatric procedures in inducing weight loss and reducing adiposity. Here we investigated the role of dietary macronutrient content on IT effects in rats. Methods Male Lewis rats consuming one of three isocaloric liquid diets enriched with fat (HF), carbohydrates (HC), or protein (HP) underwent IT or sham surgery. Body weight, energy intake, energy efficiency, body composition, and (meal-induced) changes in plasma GIP, GLP-1, PYY, neurotensin, and insulin levels were measured. Results Following IT, HC intake remained highest leading to smallest weight loss among dietary groups. IT in HF rats caused high initial weight loss and profound hypophagia, but the rats caught up later, and finally had the highest body fat content among IT rats. HP diet most efficaciously supported IT-induced reduction in body weight and adiposity, but (as opposed to other diet groups) lean mass was also reduced. Energy efficiency decreased immediately after IT irrespective of diet, but normalized later. Energy intake alone explained variation in post-operative weight change by 80%. GLP-1, neurotensin, and PYY were upregulated by IT, particularly during (0–60 min) and following 17-h post-ingestive intake, with marginal diet effects. Thirty-day post-operative cumulative energy intake was negatively correlated to 17-h post-ingestive PYY levels, explaining 47% of its variation. Conclusion Reduction in energy intake underlies IT-induced weight loss, with highest efficacy of the HP diet. PYY, GLP-1, and neurotensin levels are upregulated by IT, of which PYY may be most specifically related to reduced intake and weight loss after IT.

show abstract

Section: Discussionsupporting

confidence: 86%

Ileal Transposition in Rats Reduces Energy Intake, Body Weight, and Body Fat Most Efficaciously When Ingesting a High-Protein Diet

et al. 2020

View full text Add to dashboard Cite

show abstract

“…Certain studies have found IL-5 to be reduced in diabetes [78], while others have found IL-5 plasma levels to be correlated with glycosylated hemoglobin in diabetic patients [62]. Similarly, increased levels of IL-5 have been shown in HFD-fed mice [90]. We also found IL-12p70 and IL-13 to be closely related to high insulin levels in APP/PS1xdb/db mice, both of which have been shown to be elevated in prediabetic patients [62].…”

Section: Discussionmentioning

confidence: 99%

Amyloid beta and diabetic pathology cooperatively stimulate cytokine expression in an Alzheimer’s mouse model

Sankar

Infante-Garcia

Weinstock

et al. 2020

J Neuroinflammation

View full text Add to dashboard Cite

Background: Diabetes is a risk factor for developing Alzheimer's disease (AD); however, the mechanism by which diabetes can promote AD pathology remains unknown. Diabetes results in diverse molecular changes in the brain, including dysregulation of glucose metabolism and loss of cerebrovascular homeostasis. Although these changes have been associated with increased Aβ pathology and increased expression of glial activation markers in APPswe/ PS1dE9 (APP/PS1) mice, there has been limited characterization, to date, of the neuroinflammatory changes associated with diabetic conditions. Methods: To more fully elucidate neuroinflammatory changes associated with diabetes that may drive AD pathology, we combined the APP/PS1 mouse model with either high-fat diet (HFD, a model of pre-diabetes), the genetic db/db model of type 2 diabetes, or the streptozotocin (STZ) model of type 1 diabetes. We then used a multiplexed immunoassay to quantify cortical changes in cytokine proteins. Results: Our analysis revealed that pathology associated with either db/db, HFD, or STZ models yielded upregulation of a broad profile of cytokines, including chemokines (e.g., MIP-1α, MIP-1β, and MCP-1) and proinflammatory cytokines, including IL-1α, IFN-γ, and IL-3. Moreover, multivariate partial least squares regression analysis showed that combined diabetic-APP/PS1 models yielded cooperatively enhanced expression of the cytokine profile associated with each diabetic model alone. Finally, in APP/PS1xdb/db mice, we found that circulating levels of Aβ1-40, Aβ1-42, glucose, and insulin all correlated with cytokine expression in the brain, suggesting a strong relationship between peripheral changes and brain pathology. Conclusions: Altogether, our multiplexed analysis of cytokines shows that Alzheimer's and diabetic pathologies cooperate to enhance profiles of cytokines reported to be involved in both diseases. Moreover, since many of the identified cytokines promote neuronal injury, Aβ and tau pathology, and breakdown of the blood-brain barrier, our data suggest that neuroinflammation may mediate the effects of diabetes on AD pathogenesis. Therefore, strategies targeting neuroinflammatory signaling, as well as metabolic control, may provide a promising strategy for intervening in the development of diabetes-associated AD.

show abstract

“…In contrast, astrogliosis (elevated levels of GFAP) and microgliosis (elevated levels of Iba1) were not observed in the hippocampus of mice exposed to HFD for 6 months (Lizarbe et al, 2019b). Denver et al (2018) showed astrogliosis and microgliosis in cortex and dentate gyrus of mice fed a HFD for 18 days, but not after 1 month, even though the expression of inflammatory genes such as IKKβ, ERK2, mTOR, NF-kB1, and TLR4 persisted upregulated for 5 months on HFD (Denver et al, 2018). It should be noted, however, that levels of GFAP or Iba1 alone might not report on changes in cellular morphology, and such simplistic assessments might contribute to reported controversies (Gzielo et al, 2017).…”

Section: Inflammation and Gliosismentioning

confidence: 95%

Brain Metabolism Alterations in Type 2 Diabetes: What Did We Learn From Diet-Induced Diabetes Models?

García-Serrano

Duarte

2020

Front. Neurosci.

View full text Add to dashboard Cite

Type 2 diabetes (T2D) is a metabolic disease with impact on brain function through mechanisms that include glucose toxicity, vascular damage and blood-brain barrier (BBB) impairments, mitochondrial dysfunction, oxidative stress, brain insulin resistance, synaptic failure, neuroinflammation, and gliosis. Rodent models have been developed for investigating T2D, and have contributed to our understanding of mechanisms involved in T2D-induced brain dysfunction. Namely, mice or rats exposed to diabetogenic diets that are rich in fat and/or sugar have been widely used since they develop memory impairment, especially in tasks that depend on hippocampal processing. Here we summarize main findings on brain energy metabolism alterations underlying dysfunction of neuronal and glial cells promoted by diet-induced metabolic syndrome that progresses to a T2D phenotype.

show abstract

Sustained high‐fat diet modulates inflammation, insulin signalling and cognition in mice and a modified xenin peptide ameliorates neuropathology in a chronic high‐fat model

Cited by 55 publications

References 45 publications

Ileal Transposition in Rats Reduces Energy Intake, Body Weight, and Body Fat Most Efficaciously When Ingesting a High-Protein Diet

Ileal Transposition in Rats Reduces Energy Intake, Body Weight, and Body Fat Most Efficaciously When Ingesting a High-Protein Diet

Amyloid beta and diabetic pathology cooperatively stimulate cytokine expression in an Alzheimer’s mouse model

Brain Metabolism Alterations in Type 2 Diabetes: What Did We Learn From Diet-Induced Diabetes Models?

Contact Info

Product

Resources

About