scholarly journals Microglia Regulate Neuronal Circuits in Homeostatic and High-Fat Diet-Induced Inflammatory Conditions

2021 ◽  
Vol 15 ◽  
Author(s):  
Xiao-Lan Wang ◽  
Lianjian Li
Keyword(s):  
High Fat Diet ◽  
Microglial Activation ◽  
Current Knowledge ◽  
Brain Diseases ◽  
High Fat ◽  
Synaptic Remodeling ◽  
Inflammatory Conditions ◽  
Cellular Debris ◽  
Neuronal Connections ◽  
Almost All

Microglia are brain resident macrophages, which actively survey the surrounding microenvironment and promote tissue homeostasis under physiological conditions. During this process, microglia participate in synaptic remodeling, neurogenesis, elimination of unwanted neurons and cellular debris. The complex interplay between microglia and neurons drives the formation of functional neuronal connections and maintains an optimal neural network. However, activation of microglia induced by chronic inflammation increases synaptic phagocytosis and leads to neuronal impairment or death. Microglial dysfunction is implicated in almost all brain diseases and leads to long-lasting functional deficiency, such as hippocampus-related cognitive decline and hypothalamus-associated energy imbalance (i.e., obesity). High-fat diet (HFD) consumption triggers mediobasal hypothalamic microglial activation and inflammation. Moreover, HFD-induced inflammation results in cognitive deficits by triggering hippocampal microglial activation. Here, we have summarized the current knowledge of microglial characteristics and biological functions and also reviewed the molecular mechanism of microglia in shaping neural circuitries mainly related to cognition and energy balance in homeostatic and diet-induced inflammatory conditions.

scholarly journals Behavioral Feeding Circuit: Dietary Fat-Induced Effects of Inflammatory Mediators in the Hypothalamus

2020 ◽  
Vol 11 ◽  
Author(s):  
Kinning Poon
Keyword(s):  
Dietary Fat ◽  
High Fat Diet ◽  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Dietary Fatty Acids ◽  
Ingestive Behavior ◽  
Fat Intake ◽  
High Fat ◽  
Dietary Fat Intake ◽  
Orexigenic Peptide

Excessive dietary fat intake has extensive impacts on several physiological systems and can lead to metabolic and nonmetabolic disease. In animal models of ingestion, exposure to a high fat diet during pregnancy predisposes offspring to increase intake of dietary fat and causes increase in weight gain that can lead to obesity, and without intervention, these physiological and behavioral consequences can persist for several generations. The hypothalamus is a region of the brain that responds to physiological hunger and fullness and contains orexigenic neuropeptide systems that have long been associated with dietary fat intake. The past fifteen years of research show that prenatal exposure to a high fat diet increases neurogenesis of these neuropeptide systems in offspring brain and are correlated to behavioral changes that induce a pro-consummatory and obesogenic phenotype. Current research has uncovered several potential molecular mechanisms by which excessive dietary fat alters the hypothalamus and involve dietary fatty acids, the immune system, gut microbiota, and transcriptional and epigenetic changes. This review will examine the current knowledge of dietary fat-associated changes in the hypothalamus and the potential pathways involved in modifying the development of orexigenic peptide neurons that lead to changes in ingestive behavior, with a special emphasis on inflammation by chemokines.

Modulation of antioxidant defence system by dietary fat in rats intoxicated with o-toluidine

2002 ◽  
Vol 21 (12) ◽  
pp. 659-665 ◽  
Author(s):  
J Jodynis-Liebert ◽  
M Murias
Keyword(s):  
Antioxidant Enzymes ◽  
Dietary Fat ◽  
High Fat Diet ◽  
Thiobarbituric Acid ◽  
High Fat ◽  
Glutathione S Transferase ◽  
Antioxidant Defence ◽  
Antioxidant Defence System ◽  
Almost All ◽  
Radical Processes

o-Toluidine was administered to rats in the diet for four weeks at levels approximately 40, 80 and 160 mg/kg b.w. per day. Two types of diet have been used, standard (4% fat) and high fat (14% fat). Activity of antioxidant enzymes, level of glutathione and thiobarbituric acid reactive substances were measured in liver. Glutathione peroxidase was significantly increased in all treated groups while glutathione S-transferase and glutathione reductase were elevated in rats fed high-fat diet. o-Toluidine slightly enhanced catalase activity regardless of the kind of diet. Superoxide dismutase was the only enzyme whose activity was lowered in almost all treated groups. Enzymatic and nonenzymatic microsomal lipid peroxidation was enhanced 2-to 3-fold in both diet groups. Reduced glutathione level in liver was 2.3-to 4.0-fold increased in all treated groups. Our findings indicate that free radical processes can be involved in the toxic effects of o-toluidine and dietary fat can modify the response of some antioxidant enzymes to this compound.

scholarly journals Modeling insulin resistance in rodents by alterations in diet: what have high-fat and high-calorie diets revealed?

2018 ◽  
Vol 314 (3) ◽  
pp. E251-E265 ◽  
Author(s):  
Lewin Small ◽  
Amanda E. Brandon ◽  
Nigel Turner ◽  
Gregory J. Cooney
Keyword(s):  
Insulin Resistance ◽  
High Fat Diet ◽  
Insulin Action ◽  
Whole Body ◽  
Dietary Energy ◽  
High Fat ◽  
Large Heterogeneity ◽  
Simple Carbohydrates ◽  
Almost All ◽  
High Calorie

For over half a century, researchers have been feeding different diets to rodents to examine the effects of macronutrients on whole body and tissue insulin action. During this period, the number of different diets and the source of macronutrients employed have grown dramatically. Because of the large heterogeneity in both the source and percentage of different macronutrients used for studies, it is not surprising that different high-calorie diets do not produce the same changes in insulin action. Despite this, diverse high-calorie diets continue to be employed in an attempt to generate a “generic” insulin resistance. The high-fat diet in particular varies greatly between studies with regard to the source, complexity, and ratio of dietary fat, carbohydrate, and protein. This review examines the range of rodent dietary models and methods for assessing insulin action. In almost all studies reviewed, rodents fed diets that had more than 45% of dietary energy as fat or simple carbohydrates had reduced whole body insulin action compared with chow. However, different high-calorie diets produced significantly different effects in liver, muscle, and whole body insulin action when insulin action was measured by the hyperinsulinemic-euglycemic clamp method. Rodent dietary models remain an important tool for exploring potential mechanisms of insulin resistance, but more attention needs to be given to the total macronutrient content and composition when interpreting dietary effects on insulin action.

Grape seed and skin extract alleviates high-fat diet-induced renal lipotoxicity and prevents copper depletion in rat

2013 ◽  
Vol 38 (3) ◽  
pp. 259-267 ◽  
Author(s):  
Kamel Charradi ◽  
Salem Elkahoui ◽  
Ines Karkouch ◽  
Ferid Limam ◽  
Ghaith Hamdaoui ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
High Fat Diet ◽  
Public Health Problem ◽  
Grape Seed ◽  
Standard Diet ◽  
Skin Extract ◽  
High Fat ◽  
Oxidative Stress Status ◽  
Almost All ◽  
Copper Depletion

Obesity is a public health problem that contributes to morbidity and mortality from diabetes, heart disease, stroke, and cancers. The purpose of this investigation was to analyse the link between obesity-induced oxidative stress, renal steatosis, and kidney dysfunction, as well as the protective effect of grape seed and skin extract. Rats were fed a standard diet or a high-fat diet for 6 weeks and were either treated or not treated with grape seed and skin extract. Fat-induced oxidative stress was evaluated in the kidney with a special emphasis on transition metals. High-fat diet induced triglyceride deposition and disturbances in kidney function parameters, which are linked to an oxidative stress status and depletion of copper from the kidney. Grape seed and skin extract abrogated almost all fat-induced kidney disturbances. Grape seed and skin extract exerted potential protection against fat-induced kidney lipotoxicity and should find potential application in other kidney-related diseases.

Serum amyloid A1 levels and amyloid deposition following a high-fat diet challenge in transgenic mice overexpressing hepatic serum amyloid A1

2016 ◽  
Vol 41 (6) ◽  
pp. 640-648 ◽  
Author(s):  
Woo Young Jang ◽  
Jain Jeong ◽  
Seonggon Kim ◽  
Min-cheol Kang ◽  
Yong Hun Sung ◽  
...  
Keyword(s):  
High Fat Diet ◽  
Amyloid Deposition ◽  
Serum Amyloid ◽  
Low Grade ◽  
High Fat ◽  
Metabolic Disturbances ◽  
Amyloid A ◽  
Inflammatory Conditions ◽  
Short Period ◽  
Serum Amyloid A1

Serum amyloid A (SAA) is an acute-phase response protein in the liver, and SAA1 is the major precursor protein involved in amyloid A amyloidosis. This amyloidosis has been reported as a complication in chronic inflammatory conditions such as arthritis, lupus, and Crohn’s disease. Obesity is also associated with chronic, low-grade inflammation and sustained, elevated levels of SAA1. However, the contribution of elevated circulating SAA1 to metabolic disturbances and their complications is unclear. Furthermore, in several recent studies of transgenic (TG) mice overexpressing SAA1 that were fed a high-fat diet (HFD) for a relatively short period, no relationship was found between SAA1 up-regulation and metabolic disturbances. Therefore, we generated TG mice overexpressing SAA1 in the liver, challenged these mice with an HFD, and investigated the influence of elevated SAA1 levels. Sustained, elevated levels of SAA1 were correlated with metabolic parameters and local cytokine expression in the liver following 16 weeks on the HFD. Moreover, prolonged consumption (52 weeks) of the HFD was associated with impaired glucose tolerance and elevated SAA1 levels and resulted in systemic SAA1-derived amyloid deposition in the kidney, liver, and spleen of TG mice. Thus, we concluded that elevated SAA1 levels under long-term HFD exposure result in extensive SAA1-derived amyloid deposits, which may contribute to the complications associated with HFD-induced obesity and metabolic disorders.

scholarly journals Short high fat diet triggers reversible and region specific effects in DCX+ hippocampal immature neurons of adolescent male mice

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Fausto Chiazza ◽  
Heather Bondi ◽  
Irene Masante ◽  
Federico Ugazio ◽  
Valeria Bortolotto ◽  
...  
Keyword(s):  
High Fat Diet ◽  
Current Knowledge ◽  
Dorsal Hippocampus ◽  
Dendritic Tree ◽  
Adolescent Male ◽  
Male Mice ◽  
High Fat ◽  
Short Period ◽  
Immature Neurons ◽  
Hypercaloric Diet

AbstractAdolescence represents a crucial period for maturation of brain structures involved in cognition. Early in life unhealthy dietary patterns are associated with inferior cognitive outcomes at later ages; conversely, healthy diet is associated with better cognitive results. In this study we analyzed the effects of a short period of hypercaloric diet on newborn hippocampal doublecortin+ (DCX) immature neurons in adolescent mice. Male mice received high fat diet (HFD) or control low fat diet (LFD) from the 5th week of age for 1 or 2 weeks, or 1 week HFD followed by 1 week LFD. After diet supply, mice were either perfused for immunohistochemical (IHC) analysis or their hippocampi were dissected for biochemical assays. Detailed morphometric analysis was performed in DCX+ cells that displayed features of immature neurons. We report that 1 week-HFD was sufficient to dramatically reduce dendritic tree complexity of DCX+ cells. This effect occurred specifically in dorsal and not ventral hippocampus and correlated with reduced BDNF expression levels in dorsal hippocampus. Both structural and biochemical changes were reversed by a return to LFD. Altogether these studies increase our current knowledge on potential consequences of hypercaloric diet on brain and in particular on dorsal hippocampal neuroplasticity.

scholarly journals Early steatohepatitis in hyperlipidemic mice with endothelial-specific gain of TRPC3 function precedes changes in aortic atherosclerosis

2016 ◽  
Vol 48 (8) ◽  
pp. 644-649 ◽  
Author(s):  
Kathryn Smedlund ◽  
Prabhatachandra Dube ◽  
Guillermo Vazquez
Keyword(s):  
High Fat Diet ◽  
Transient Receptor Potential ◽  
Metabolic Diseases ◽  
Current Knowledge ◽  
Early Stage ◽  
Developed Countries ◽  
Vascular Pathology ◽  
Aortic Atherosclerosis ◽  
High Fat ◽  
Liver Sinusoid

Nonalcoholic fatty liver disease (NAFLD) and its more advanced form nonalcoholic steatohepatitis (NASH) are the most common chronic liver diseases in developed countries. Moreover, NAFLD and NASH are considerable risk factors for atherosclerosis, the most frequent vascular pathology in these and other metabolic diseases. Despite this strong connection, current knowledge of the relationship between NAFLD/NASH and atherosclerosis is scarce. Recently, we studied hyperlipidemic Apoe knockout mice with endothelial-specific gain of transient receptor potential canonical 3 channel function (TgESTRPC3/ApoeKO) and found that these animals had increased burden of advanced aortic atherosclerosis (16 wk on high-fat diet) compared with nontransgenic ApoeKO littermate controls (non-Tg/ApoeKO), whereas early lesions (10 wk on high-fat diet) were not different. Here, we report that at the early stage when differences in aortic atherosclerosis are not yet manifest, the livers of TgESTRPC3/ApoeKO mice show steatosis, fibrosis, and altered hepatic enzymes compared with non-Tg/ApoeKO animals. Because differences in liver pathology were noticeable long before differences in atherosclerosis were evident, our studies suggest that TRPC3-related endothelial mechanisms that promote steatohepatitis may also contribute to atherosclerosis progression. In vitro, downregulation of TRPC3 in liver sinusoid endothelial cells reduces their susceptibility to endoplasmic reticulum stress-induced apoptosis, suggesting that a proapoptotic effect of TRPC3 may add to other fibrogenic factors in vivo. These novel findings show a positive association between augmented expression of an endothelial TRPC channel, development of early steatohepatitis, and atherosclerotic burden in a hyperlipidemic mouse model of NAFLD fed conventional Western-type diet.

scholarly journals Irinotecan-Induced Steatohepatitis: Current Insights

2021 ◽  
Vol 11 ◽  
Author(s):  
Jun Han ◽  
Jing Zhang ◽  
Chengliang Zhang
Keyword(s):  
Colorectal Cancer ◽  
Body Mass Index ◽  
High Fat Diet ◽  
Current Knowledge ◽  
High Body Mass Index ◽  
Research Progress ◽  
High Fat ◽  
Colorectal Cancer Liver Metastasis ◽  
Therapeutic Drugs ◽  
Lobular Inflammation

The hepatotoxicity of irinotecan is drawing wide concern nowadays due to the widespread use of this chemotherapeutic against various solid tumors, particularly metastatic colorectal cancer. Irinotecan-induced hepatotoxicity mainly manifests as transaminase increase and steatosis with or without transaminase increase, and is accompanied by vacuolization, and lobular inflammation. Irinotecan-induced steatohepatitis (IIS) increases the risk of morbidity and mortality in patients with colorectal cancer liver metastasis (CRCLM). The major risks and predisposing factors for IIS include high body mass index (BMI) or obesity, diabetes, and high-fat diet. Mitochondrial dysfunction and autophagy impairment may be involved in the pathogenesis of IIS. However, there is currently no effective preventive or therapeutic treatment for this condition. Thus, the precise mechanisms underlying the pathogenesis of IIS should be deciphered for the development of therapeutic drugs. This review summarizes the current knowledge and research progress on IIS.

scholarly journals CX3CL1 action on microglia protects from diet-induced obesity by restoring POMC neuronal excitability and melanocortin system activity impaired by high-fat diet feeding

2021 ◽  
Author(s):  
Jineta Banerjee ◽  
Mauricio D. Dorfman ◽  
Rachael Fasnacht ◽  
John D. Douglass ◽  
Alice C. Wyse-Jackson ◽  
...  
Keyword(s):  
High Fat Diet ◽  
Microglial Activation ◽  
Molecular Mechanisms ◽  
Melanocortin Receptor ◽  
High Fat ◽  
Diet Induced Obesity ◽  
Leptin Sensitivity ◽  
Neuron Excitability ◽  
Melanocortin Signaling

Objective: Diet-induced obesity (DIO) is associated with hypothalamic microglial activation and dysfunction of the melanocortin pathway, but the molecular mechanisms linking the two remain unclear. Previous studies have hypothesized that microglial inflammatory signaling is linked with impaired pro-opiomelanocortin (POMC) neuron function, but this mechanism has never been directly tested in vivo. We addressed this hypothesis using the specific microglial silencing molecule, CX3CL1 (fractalkine), to determine whether reducing hypothalamic microglial activation can restore POMC/melanocortin signaling in the brain to protect against DIO. Methods: We performed metabolic analyses in mice with targeted viral overexpression of CX3CL1 in the hypothalamus exposed to high fat diet (HFD). Electrophysiologic recording in hypothalamic slices from POMC-MAPT-GFP mice was used to determine the effects of HFD feeding and microglial silencing via minocycline or CX3CL1 on GFP-labeled POMC neurons. Finally, mice with hypothalamic overexpression of CX3CL1 received central treatment with the melanocortin receptor antagonist SHU-9119 to determine whether melanocortin signaling is required for the metabolic benefits of CX3CL1. Results: We found that targeted expression of both soluble and membrane-bound forms of CX3CL1 in the mediobasal hypothalamus potently reduced weight gain and increased leptin sensitivity in animals exposed to high fat diet. The protective effect of CX3CL1 rescued diet-induced changes in POMC neuron excitability and required intact melanocortin receptor signaling in vivo. Conclusion: Our results provide the first evidence that HFD-induced POMC neuron dysfunction involves microglial activation. Furthermore, our study suggests that the anti-obesity action of CX3CL1 is mediated through the restoration of POMC neuron excitability and melanocortin signaling.

Abstract 406: Flavocoxid a Dual Cox/Lox Inhibitor Reduces Atherosclerosis Development in ApoE KO Mice Fed With a Western High Fat Diet

2017 ◽  
Vol 37 (suppl_1) ◽  
Author(s):  
Alessandra Bitto ◽  
Gabriele Pizzino ◽  
Giovanni Pallio ◽  
Federica Mannino ◽  
Natasha Irrera ◽  
...  
Keyword(s):  
High Fat Diet ◽  
The Body ◽  
Oral Suspension ◽  
Blood Levels ◽  
High Fat ◽  
Clinical Model ◽  
Knock Out ◽  
Atherosclerotic Burden ◽  
Inflammatory Conditions ◽  
Atherosclerosis Development

Flavocoxid is composed by two flavonoids, baicalin and catechin and it exerts anti-inflammatory effect blocking the peroxidase activity of COX1/2 and 5-LOX. This balanced inhibition prevents the development of adverse effects as demonstrated in clinical trials. The antinflammatory effect of flavocoxid was tested in ApoE knock out mice fed with a high fat western diet. Mice (of both sex) were 5 weeks old at the beginning of the experiment and were fed with a high fat diet for 8 weeks. Mice were randomized to receive: vehicle, or simvastatin (40mg/kg/day by oral suspension), or flavocoxid by oral suspension at the human equivalent dose of 500 mg/day (20mg/kg/day) that was previously reported effective in other inflammatory conditions. The body weight, food intake, cholesterol, and triglyceride levels were recorded every week and at the time of sacrifice the thoracic aorta, liver, and blood samples were taken. Flavocoxid supplementation reduced blood levels of triglycerides and cholesterol and the extent of atherosclerotic plaques. In liver samples the mRNA expression of PPAR-alpha and SREBP-1 was significantly affected by flavocoxid supplementation (p less than 0.05 vs untreated ApoE mice), and the western blot analysis demonstrated an increased expression of the AMPK-alpha kinase demonstrating increased cellular metabolism in treated animals (p less than 0.05 vs untreated ApoE mice). The positive results obtained in this pre-clinical model further support the use of flavocoxid to reduce the atherosclerotic burden.

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