Cognitive impairment following high fat diet consumption is associated with brain inflammation

Pistell, Paul J.; Morrison, Christopher D.; Gupta, Sunita; Knight, Alecia G.; Keller, Jeffrey N.; Ingram, Donald K.; Bruce‐Keller, Annadora J.

doi:10.1016/j.jneuroim.2009.11.010

Cited by 512 publications

(407 citation statements)

References 85 publications

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“…Studies from our laboratory and others' have demonstrated that HFDs exacerbate tissue dysfunction in aging animals (11,29,46,68,76). Additionally, studies from our laboratory and others' have shown that HFDs promote much greater amounts of adipose gain, and presumably adipose tissue dysfunction, compared with younger animals (46,50,66). These data point to important, and as yet unknown, interactions between obesity and aging.…”

Section: Discussionmentioning

confidence: 53%

Aging is associated with hypoxia and oxidative stress in adipose tissue: implications for adipose function

Zhang

Ebenezer

Dasuri

et al. 2011

American Journal of Physiology-Endocrinology and Metabolism

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As a part of aging there are known to be numerous alterations which occur in multiple tissues of the body, and the focus of this study was to determine the extent to which oxidative stress and hypoxia occur during adipose tissue aging. In our studies we demonstrate for the first time that aging is associated with both hypoxia (38% reduction in oxygen levels, Po2 21.7 mmHg) and increases reactive oxygen species in visceral fat depots of aging male C57Bl/6 mice. Interestingly, aging visceral fat depots were observed to have significantly less change in the expression of genes involved in redox regulation compared with aging subcutaneous fat tissue. Exposure of 3T3-L1 adipocytes to the levels of hypoxia observed in aging adipose tissue was sufficient to alter multiple aspects of adipose biology inducing increased levels of in insulin-stimulated glucose uptake and decreased lipid content. Taken together, these data demonstrate that hypoxia and increased levels of reactive oxygen species occur in aging adipose tissue, highlighting the potential for these two stressors as potential modulators of adipose dysfunction during aging.

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Section: Discussionmentioning

confidence: 53%

Aging is associated with hypoxia and oxidative stress in adipose tissue: implications for adipose function

Zhang

Ebenezer

Dasuri

et al. 2011

American Journal of Physiology-Endocrinology and Metabolism

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“…52). Some of these peripheral effects, such as oxidative stress, also occur in the brain following HF feeding (21,40,58), and HF feeding increases cognitive impairment, tau deposition, MPTP vulnerability, and inflammation in the brain (15,38,44,45). Although specific contributions of other HF diet effects cannot be ruled out, our observation of increased markers of insulin resistance in the absence of increased total cholesterol or LDL-C levels and a positive correlation between HOMA-IR and DA depletion support a role for insulin resistance in mediating increased toxin-induced DA depletion.…”

Section: Discussionmentioning

confidence: 99%

Neurodegeneration in an animal model of Parkinson's disease is exacerbated by a high-fat diet

Morris

Bomhoff

Stanford

et al. 2010

American Journal of Physiology-Regulatory, Integrative and Comp

129

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(PD), the clinical literature remains equivocal. We, therefore, sought to address the relationship between insulin resistance and nigrostriatal dopamine (DA) in a preclinical animal model. High-fat feeding in rodents is an established model of insulin resistance, characterized by increased adiposity, systemic oxidative stress, and hyperglycemia. We subjected rats to a normal chow or high-fat diet for 5 wk before infusing 6-hydroxydopamine (6-OHDA) into the medial forebrain bundle. Our goal was to determine whether a high-fat diet and the resulting peripheral insulin resistance would exacerbate 6-OHDA-induced nigrostriatal DA depletion. Prior to 6-OHDA infusion, animals on the high-fat diet exhibited greater body weight, increased adiposity, and impaired glucose tolerance. Two weeks after 6-OHDA, locomotor activity was tested, and brain and muscle tissue was harvested. Locomotor activity did not differ between the groups nor did cholesterol levels or measures of muscle atrophy. High-fat-fed animals exhibited higher homeostatic model assessment of insulin resistance (HOMA-IR) values and attenuated insulin-stimulated glucose uptake in fast-twitch muscle, indicating decreased insulin sensitivity. Animals in the high-fat group also exhibited greater DA depletion in the substantia nigra and the striatum, which correlated with HOMA-IR and adiposity. Decreased phosphorylation of HSP27 and degradation of IB␣ in the substantia nigra indicate increased tissue oxidative stress. These findings support the hypothesis that a diet high in fat and the resulting insulin resistance may lower the threshold for developing PD, at least following DA-specific toxin exposure. dopamine; diabetes; substantia nigra; striatum; insulin resistance CLINICAL STUDIES SUGGEST A LINK between type 2 diabetes (T2D) and Parkinson's disease (PD) (30,46), and between fat intake or adiposity and PD (1, 31, 34). Moreover, it was reported over 40 years ago that greater than 50% of PD patients exhibit abnormal glucose tolerance (4, 10) or diabetes (36). Despite this information, very little is known regarding the relationship of these diseases and the impact of comorbidity on their pathogenesis. By 2025, T2D is estimated to impact 300 million individuals (47), with the elderly at greatest risk (54), the population also at greatest risk for neurodegenerative diseases like PD. For these reasons, understanding the potential for T2D, obesity, high dietary fat intake, and insulin resistance to contribute to PD is critical. Although the exact cause of PD is unknown, various environmental factors such as aging, diet, and environmental toxin exposure have been implicated in contributing to its development (29, 34, 51). The idea that "multiple hits" play a role in PD degeneration is supported by the fact that 80% of dopamine (DA)-producing neurons must be lost for symptoms to appear (50). While diabetes and PD do not invariably coincide, several studies suggest that obesity may potentiate neuronal dysfunction or even neurodegeneration (reviewed in Ref. 11). High-f...

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“…Obesity is now considered an 'inflammatory condition' that is associated with elevated peripheral and vascular pro-inflammatory profiles (Scarpellini and Tack 2012;Sun et al 2012) and central inflammatory changes including gliosis and activation of the cerebrovasculature in the brains of obese and high-fat fed rodents (Pistell et al 2010;Drake et al 2011;Thaler et al 2012). It is generally considered that peripheral inflammation is a consequence of obesity, however, recent data suggests that central inflammation actually precedes weight gain in high-fat fed rodents (Thaler et al 2012).…”

Section: Obesity/metabolic Syndromementioning

confidence: 99%

The Immune System in Stroke: Clinical Challenges and Their Translation to Experimental Research

Smith

Lawrence

Rodriguez‐Grande

et al. 2013

J Neuroimmune Pharmacol

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Stroke represents an unresolved challenge for both developed and developing countries and has a huge socio-economic impact. Although considerable effort has been made to limit stroke incidence and improve outcome, strategies aimed at protecting injured neurons in the brain have all failed. This failure is likely to be due to both the incompleteness of modelling the disease and its causes in experimental research, and also the lack of understanding of how systemic mechanisms lead to an acute cerebrovascular event or contribute to outcome.Inflammation has been implicated in all forms of brain injury and it is now clear that immune mechanisms profoundly influence (and are responsible for the development of) risk and causation of stroke, and the outcome following the onset of cerebral ischemia. Until very recently, systemic inflammatory mechanisms, with respect to common comorbidities in stroke, have largely been ignored in experimental studies. The main aim is therefore to understand interactions between the immune system and brain injury in order to develop novel therapeutic approaches. Recent data from clinical and experimental research clearly show that systemic inflammatory diseases -such as atherosclerosis, obesity, diabetes or infectionsimilar to stress and advanced age, are associated with dysregulated immune responses which can profoundly contribute to cerebrovascular inflammation and injury in the central nervous system. In this review, we summarize recent advances in the field of inflammation and stroke, focusing on the challenges of translation between pre-clinical and clinical studies, and potential anti-inflammatory/immunomodulatory therapeutic approaches.

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Cognitive impairment following high fat diet consumption is associated with brain inflammation

Cited by 512 publications

References 85 publications

Aging is associated with hypoxia and oxidative stress in adipose tissue: implications for adipose function

Aging is associated with hypoxia and oxidative stress in adipose tissue: implications for adipose function

Neurodegeneration in an animal model of Parkinson's disease is exacerbated by a high-fat diet

The Immune System in Stroke: Clinical Challenges and Their Translation to Experimental Research

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