Obesity-Induced Neuroinflammation: Beyond the Hypothalamus

Guillemot-Legris, Owein; Muccioli, Giulio G.

doi:10.1016/j.tins.2017.02.005

Cited by 430 publications

(333 citation statements)

References 111 publications

Supporting

Mentioning

312

Contrasting

Unclassified

Order By: Relevance

“…Interestingly, we did not observe increases in expression of pro-inflammatory cytokines with HFD. Although diet-induced obesity increases features of neuroinflammation including glial activation [83], obesogenic diets often do not yield increased cytokine expression [84] or do so in a brain-region specific manner [85] even with evidence of significant microglial activation [86]. This disconnection between microglial activation and cytokine expression may be especially prevalent in female mice, which are relatively resistant to HFD [38, 87].…”

Section: Discussionmentioning

confidence: 99%

Age-dependent regulation of obesity and Alzheimer-related outcomes by hormone therapy in female 3xTg-AD mice

Christensen

Pike

2017

PLoS ONE

View full text Add to dashboard Cite

Depletion of ovarian hormones at menopause is associated with increased Alzheimer’s disease (AD) risk. Hormone loss also increases central adiposity, which promotes AD development. One strategy to improve health outcomes in postmenopausal women is estrogen-based hormone therapy (HT), though its efficacy is controversial. The window of opportunity hypothesis posits that HT is beneficial only if initiated near the onset of menopause. Here, we tested this hypothesis by assessing the efficacy of HT against diet-induced obesity and AD-related pathology in female 3xTg-AD mice at early versus late middle-age. HT protected against obesity and reduced β-amyloid burden only at early middle-age. One mechanism that contributes to AD pathogenesis is microglial activation, which is increased by obesity and reduced by estrogens. In parallel to its effects on β-amyloid accumulation, we observed that HT reduced morphological evidence of microglial activation in early but not late middle-age. These findings suggest that HT may be effective during human perimenopause in reducing indices of obesity and AD-related pathology, a conclusion consistent with the window of opportunity hypothesis.

show abstract

Section: Discussionmentioning

confidence: 99%

Age-dependent regulation of obesity and Alzheimer-related outcomes by hormone therapy in female 3xTg-AD mice

Christensen

Pike

2017

PLoS ONE

View full text Add to dashboard Cite

show abstract

“…[86] Further, diet-induced obesity is associated with a neuroinflammatory profile across a range of brain regions, including the amygdala, and it has been hypothesized that one mechanism for this diet-induced neuroinflammation is through alterations in the microbiota. [87] Overall, it is clear that there are many routes by which the microbiota might influence the amygdala.…”

Section: Immune Modulation Is a Key Communication Pathway In The Micrmentioning

confidence: 99%

Gutsy Moves: The Amygdala as a Critical Node in Microbiota to Brain Signaling

et al. 2017

View full text Add to dashboard Cite

The amygdala is a key brain area regulating responses to stress and emotional stimuli, so improving our understanding of how it is regulated could offer novel strategies for treating disturbances in emotion regulation. As we review here, a growing body of evidence indicates that the gut microbiota may contribute to a range of amygdala-dependent brain functions from pain sensitivity to social behavior, emotion regulation, and therefore, psychiatric health. In addition, it appears that the microbiota is necessary for normal development of the amygdala at both the structural and functional levels. While further investigations are needed to elucidate the exact mechanisms of microbiota-to-amygdala communication, ultimately, this work raises the intriguing possibility that the gut microbiota may become a viable treatment target in disorders associated with amygdala dysregulation, including visceral pain, post-traumatic stress disorder, and beyond. Also see the video abstract here: https://youtu.be/O5gvxVJjX18

show abstract

“…The origin of the increased metabolism during insulin stimulation in the obesity group is putative, but it is possible that it relates to neuroinflammation and glial hyperplasia. Both events have been clearly identified in the hypothalamus and in the hippocampus during obesity . We ascertained a change in metabolic connectivity for the hippocampus in the obesity group, together with an activation cluster in the obesity group during insulin stimulation.…”

Section: Discussionmentioning

confidence: 99%

Inward Glucose Transfer Accounts for Insulin‐Dependent Increase in Brain Glucose Metabolism Associated with Diet‐Induced Obesity

Bahri

Horowitz

Malbert³

2018

Obesity

View full text Add to dashboard Cite

Whole-body insulin sensitivity was reduced by more than 50% in the obesity group. During insulin stimulation, whole-brain insulin-induced increased glucose uptake was unaltered in lean animals but increased markedly in the animals with obesity. The increased glucose uptake reflected an increase in the inward transfer without changes in phosphorylation or outward brain transport. Connectivity was increased in the animals with obesity CONCLUSIONS: Diet-induced obesity is associated with an increase in insulin-stimulated brain glucose uptake as a consequence of a larger inward transfer. These changes occurred together with an increased connectivity in reference to regions associated with memory recollection.

show abstract

Obesity-Induced Neuroinflammation: Beyond the Hypothalamus

Cited by 430 publications

References 111 publications

Age-dependent regulation of obesity and Alzheimer-related outcomes by hormone therapy in female 3xTg-AD mice

Age-dependent regulation of obesity and Alzheimer-related outcomes by hormone therapy in female 3xTg-AD mice

Gutsy Moves: The Amygdala as a Critical Node in Microbiota to Brain Signaling

Inward Glucose Transfer Accounts for Insulin‐Dependent Increase in Brain Glucose Metabolism Associated with Diet‐Induced Obesity

Contact Info

Product

Resources

About