Flavonoids in adipose tissue inflammation and atherosclerosis: one arrow, two targets

2020 ◽  
Vol 134 (12) ◽  
pp. 1403-1432 ◽  
Author(s):  
Manal Muin Fardoun ◽  
Dina Maaliki ◽  
Nabil Halabi ◽  
Rabah Iratni ◽  
Alessandra Bitto ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Fruits And Vegetables ◽  
Metabolic Diseases ◽  
Therapeutic Agents ◽  
Adipose Tissue Inflammation ◽  
Cellular Mechanisms ◽  
Tissue Inflammation ◽  
Cholesterol Levels ◽  
Naturally Occurring ◽  
Pro Inflammatory Cytokines

Abstract Flavonoids are polyphenolic compounds naturally occurring in fruits and vegetables, in addition to beverages such as tea and coffee. Flavonoids are emerging as potent therapeutic agents for cardiovascular as well as metabolic diseases. Several studies corroborated an inverse relationship between flavonoid consumption and cardiovascular disease (CVD) or adipose tissue inflammation (ATI). Flavonoids exert their anti-atherogenic effects by increasing nitric oxide (NO), reducing reactive oxygen species (ROS), and decreasing pro-inflammatory cytokines. In addition, flavonoids alleviate ATI by decreasing triglyceride and cholesterol levels, as well as by attenuating inflammatory mediators. Furthermore, flavonoids inhibit synthesis of fatty acids and promote their oxidation. In this review, we discuss the effect of the main classes of flavonoids, namely flavones, flavonols, flavanols, flavanones, anthocyanins, and isoflavones, on atherosclerosis and ATI. In addition, we dissect the underlying molecular and cellular mechanisms of action for these flavonoids. We conclude by supporting the potential benefit for flavonoids in the management or treatment of CVD; yet, we call for more robust clinical studies for safety and pharmacokinetic values.

scholarly journals A Novel Combination of Fruits and Vegetables Prevents Diet-Induced Hepatic Steatosis and Metabolic Dysfunction in Mice

2020 ◽  
Vol 150 (11) ◽  
pp. 2950-2960
Author(s):  
Weimin Guo ◽  
Dayong Wu ◽  
Maria C Dao ◽  
Lijun Li ◽  
Erin D Lewis ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Weight Gain ◽  
Gut Microbiota ◽  
Hepatic Steatosis ◽  
Fruits And Vegetables ◽  
Causal Relation ◽  
Adipose Tissue Inflammation ◽  
Tissue Inflammation ◽  
Freeze Dried ◽  
Underlying Mechanisms

ABSTRACT Background Epidemiological studies suggest that higher fruits and vegetables (F&V) consumption correlates with reduced risk of hepatic steatosis, yet evidence for causality and the underlying mechanisms is lacking. Objectives We aimed to determine the causal relation between F&V consumption and improved metabolic disorders in mice fed high-fat (HF) (Experiment-1) or normal-fat (Experiment-2) diets and its underlying mechanisms. Methods Six-week-old male C57BL/6J mice were randomly grouped and fed diets supplemented at 0%–15% (wt:wt) with a freeze-dried powder composed of 24 commonly consumed F&V (human equivalent of 0–9 servings/d) for 20 wk. In Experiment-1, mice were fed an HF (45% kcal fat) diet with 0% (HF0), 5%, 10%, or 15% (HF15) F&V or a matched low-fat control diet (10% kcal fat). In Experiment-2, mice were fed an AIN-93 diet (basal) (B, 16% kcal fat) with 0% (B0), 5%, 10%, or 15% (B15) F&V supplementation. Body weight and composition, food intake, hepatic steatosis, inflammation, ceramide levels, sphingomyelinase activity, and gut microbiota were assessed. Results In Experiment-1, mice fed the HF15 diet had lower weight gain (17.9%), hepatic steatosis (48.4%), adipose tissue inflammation, blood (24.6%) and liver (33.9%) ceramide concentrations, and sphingomyelinase activity (38.8%) than HF0 mice (P < 0.05 for all). In Experiment-2, mice fed the B15 diet had no significant changes in weight gain but showed less hepatic steatosis (28.5%), blood and adipose tissue inflammation, and lower blood (30.0%) ceramide concentrations than B0 mice (P < 0.05 for all). These F&V effects were associated with favorable microbiota changes. Conclusions These findings represent the first evidence for a causal role of high F&V intake in mitigating hepatic steatosis in mice. These beneficial effects may be mediated through changes in ceramide and/or gut microbiota, and suggest that higher than currently recommended servings of F&V may be needed to achieve maximum health benefits.

scholarly journals The Role of the Immune System in Obesity and Insulin Resistance

2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Payal S. Patel ◽  
Eric D. Buras ◽  
Ashok Balasubramanyam
Keyword(s):  
Insulin Resistance ◽  
Adipose Tissue ◽  
Immune System ◽  
Stress Responses ◽  
Innate Immune System ◽  
Metabolic Diseases ◽  
Innate Immune ◽  
Metabolic Dysfunction ◽  
Adipose Tissue Inflammation ◽  
Tissue Inflammation

The innate immune system provides organisms with rapid and well-coordinated protection from foreign pathogens. However, under certain conditions of metabolic dysfunction, components of the innate immune system may be activated in the absence of external pathogens, leading to pathologic consequences. Indeed, there appears to be an intimate relationship between metabolic diseases and immune dysfunction; for example, macrophages are prime players in the initiation of a chronic inflammatory state in obesity which leads to insulin resistance. In response to increases in free fatty acid release from obese adipose depots, M1-polarized macrophages infiltrate adipose tissues. These M1 macrophages trigger inflammatory signaling and stress responses within cells that signal through JNK or IKKβpathways, leading to insulin resistance. If overnutrition persists, mechanisms that counteract inflammation (such as M2 macrophages and PPAR signaling) are suppressed, and the inflammation becomes chronic. Although macrophages are a principal constituent of obese adipose tissue inflammation, other components of the immune system such as lymphocytes and mast cells also contribute to the inflammatory cascade. Thus it is not merely an increased mass of adipose tissue that directly leads to attenuation of insulin action, but rather adipose tissue inflammation activated by the immune system in obese individuals that leads to insulin resistance.

scholarly journals SGLT2i and GLP-1RA in Cardiometabolic and Renal Diseases: From Glycemic Control to Adipose Tissue Inflammation and Senescence

2021 ◽  
Vol 2021 ◽  
pp. 1-17
Author(s):  
Luis D'Marco ◽  
Valery Morillo ◽  
José Luis Gorriz ◽  
María K. Suarez ◽  
Manuel Nava ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Glycemic Control ◽  
Molecular Mechanisms ◽  
Metabolic Diseases ◽  
Renal Diseases ◽  
Diabetic Patients ◽  
Adipose Tissue Inflammation ◽  
Tissue Inflammation ◽  
First Line Therapy ◽  
Anti Inflammatory

Background. Over the last few years, the use of sodium-glucose cotransporter 2 inhibitors (SGLT2i) and glucagon-like peptide 1 receptor agonists (GLP-1RA) has increased substantially in medical practice due to their documented benefits in cardiorenal and metabolic health. In this sense, and in addition to being used for glycemic control in diabetic patients, these drugs also have other favorable effects such as weight loss and lowering blood pressure, and more recently, they have been shown to have cardio and renoprotective effects with anti-inflammatory properties. Concerning the latter, the individual or associated use of these antihyperglycemic agents has been linked with a decrease in proinflammatory cytokines and with an improvement in the inflammatory profile in chronic endocrine-metabolic diseases. Hence, these drugs have been positioned as first-line therapy in the management of diabetes and its multiple comorbidities, such as obesity, which has been associated with persistent inflammatory states that induce dysfunction of the adipose tissue. Moreover, other frequent comorbidities in long-standing diabetic patients are chronic complications such as diabetic kidney disease, whose progression can be slowed by SGLT2i and/or GLP-1RA. The neuroendocrine and immunometabolism mechanisms underlying adipose tissue inflammation in individuals with diabetes and cardiometabolic and renal diseases are complex and not fully understood. Summary. This review intends to expose the probable molecular mechanisms and compile evidence of the synergistic or additive anti-inflammatory effects of SGLT2i and GLP-1RA and their potential impact on the management of patients with obesity and cardiorenal compromise.

scholarly journals Obesity-Induced Adipose Tissue Inflammation as a Strong Promotional Factor for Pancreatic Ductal Adenocarcinoma

Cells ◽  
2019 ◽  
Vol 8 (7) ◽  
pp. 673 ◽  
Author(s):  
Hui-Hua Chang ◽  
Guido Eibl
Keyword(s):  
Adipose Tissue ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Visceral Adipose Tissue ◽  
Metabolic Diseases ◽  
The United States ◽  
Ductal Adenocarcinoma ◽  
Adipose Tissue Inflammation ◽  
Tissue Inflammation ◽  
Genetically Engineered Mouse Model ◽  
Visceral Adipose

Pancreatic ductal adenocarcinoma (PDAC) is expected to soon become the second leading cause of cancer related deaths in the United States. This may be due to the rising obesity prevalence, which is a recognized risk factor for PDAC. There is great interest in deciphering the underlying driving mechanisms of the obesity–PDAC link. Visceral adiposity has a strong correlation to certain metabolic diseases and gastrointestinal cancers, including PDAC. In fact, our own data strongly suggest that visceral adipose tissue inflammation is a strong promoter for PDAC growth and progression in a genetically engineered mouse model of PDAC and diet-induced obesity. In this review, we will discuss the relationship between obesity-associated adipose tissue inflammation and PDAC development, with a focus on the key molecular and cellular components in the dysfunctional visceral adipose tissue, which provides a tumor permissive environment.

Metabolic inflammation: role of cytokines in the crosstalk between adipose tissue and liver

2013 ◽  
Vol 91 (11) ◽  
pp. 867-872 ◽  
Author(s):  
Romana R. Gerner ◽  
Verena Wieser ◽  
Alexander R. Moschen ◽  
Herbert Tilg
Keyword(s):  
Morbid Obesity ◽  
Adipose Tissue ◽  
Inflammatory Cytokines ◽  
Severe Obesity ◽  
The Body ◽  
Rapid Weight Loss ◽  
Adipose Tissue Inflammation ◽  
Tissue Inflammation ◽  
Metabolic Inflammation ◽  
Pro Inflammatory Cytokines

The innate immune system and its major mediators, i.e., cytokines, are increasingly recognized as being of crucial importance in metabolic inflammation as observed in morbid obesity and type 2 diabetes (T2D). Morbid obesity is commonly associated with adipose tissue inflammation. Adipose tissue inflammation is characterized by an increased expression of various pro-inflammatory cytokines such as tumor necrosis factor-alpha, interleukin-1 and -6, and by a rather heterogenous cellular infiltrate including monocytes/macrophages, neutrophils, B lymphocytes, T lymphocytes, and others. It has been demonstrated that in patients with severe obesity and fatty liver disease, expression of these pro-inflammatory cytokines in adipose tissue is 100–1000 times higher compared with that in the liver. Therefore, the adipose tissue can be considered in the state of severe obesity as the “cytokine factory” of the body. Rapid weight loss almost entirely eliminates pro-inflammatory cytokines in the adipose tissue, and therefore provides a very potent anti-inflammatory strategy. In conclusion, there is increasing evidence that peripheral tissues such as the adipose tissue may affect disease processes in target organs such as the liver, pancreas, heart, or blood vessels, and may therefore significantly contribute to chronic inflammation as observed in obesity and T2D.

scholarly journals Distinct Influence of Hypercaloric Diets Predominant with Fat or Fat and Sucrose on Adipose Tissue and Liver Inflammation in Mice

Molecules ◽  
2020 ◽  
Vol 25 (19) ◽  
pp. 4369
Author(s):  
Caíque S. M. Fonseca ◽  
Joshua E. Basford ◽  
David G. Kuhel ◽  
Eddy S. Konaniah ◽  
James G. Cash ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Dietary Fat ◽  
Metabolic Diseases ◽  
Liver Steatosis ◽  
Carbohydrate Intake ◽  
Caloric Content ◽  
Adipose Tissue Inflammation ◽  
High Fat ◽  
Disease Manifestation ◽  
Tissue Inflammation

Overfeeding of a hypercaloric diet leads to obesity, diabetes, chronic inflammation, and fatty liver disease. Although limiting fat or carbohydrate intake is the cornerstone for obesity management, whether lowering fat or reducing carbohydrate intake is more effective for health management remains controversial. This study used murine models to determine how dietary fat and carbohydrates may influence metabolic disease manifestation. Age-matched C57BL/6J mice were fed 2 hypercaloric diets with similar caloric content, one with very high fat and low carbohydrate content (VHF) and the other with moderately high fat levels with high sucrose content (HFHS) for 12 weeks. Both groups gained more weight and displayed hypercholesterolemia, hyperglycemia, hyperinsulinemia, and liver steatosis compared to mice fed a normal low-fat (LF) diet. Interestingly, the VHF-fed mice showed a more robust adipose tissue inflammation compared to HFHS-fed mice, whereas HFHS-fed mice showed liver fibrosis and inflammation that was not observed in VHF-fed mice. Taken together, these results indicate macronutrient-specific tissue inflammation with excess dietary fat provoking adipose tissue inflammation, whereas moderately high dietary fat with extra sucrose is necessary and sufficient for hepatosteatosis advancement to steatohepatitis. Hence, liver and adipose tissues respond to dietary fat and sucrose in opposite manners, yet both macronutrients are contributing factors to metabolic diseases.

Heat shock proteins in obesity: links to cardiovascular disease

2015 ◽  
Vol 21 (2) ◽  
Author(s):  
Christiane Habich ◽  
Henrike Sell
Keyword(s):  
Cardiovascular Disease ◽  
Adipose Tissue ◽  
Heat Shock ◽  
Metabolic Diseases ◽  
Current Knowledge ◽  
Tissue Expansion ◽  
Heme Oxygenase 1 ◽  
Adipose Tissue Inflammation ◽  
Tissue Inflammation ◽  
Shock Proteins

AbstractAdipose tissue expansion is associated with adipocyte dysfunction and increased inflammatory processes. In the obese state, adipose tissue is characterized by an impaired intracellular stress defense system and dysbalanced heat shock response. Several members of the heat shock protein (HSP) family have been identified as novel adipokines released upon cellular stress, which might be a molecular link from adipose tissue inflammation to the cardiovascular system. Therefore, this review aims at summarizing and discussing our recent knowledge on HSPs in relation to obesity and their potential links to cardiovascular disease. Of particular importance/interest are two members of the HSP family, HSP60 and heme oxygenase 1 (HO-1), which have been well described as adipokines, and studied in the context of obesity and cardiovascular disease. HSP60 is regarded as a novel molecular link between adipose tissue inflammation and obesity-associated insulin resistance. The role of HO-1 induction in the obese state is well-documented, but a causal relationship between increased HO-1 levels and obesity-associated metabolic diseases is still controversial. Both HSP60 and HO-1 are also forthcoming targets for the treatment of cardiovascular disease, and the current knowledge will also be discussed in this review.

Adipose tissue inflammation: a cause or consequence of obesity-related insulin resistance?

2016 ◽  
Vol 130 (18) ◽  
pp. 1603-1614 ◽  
Author(s):  
Matthias Blüher
Keyword(s):  
Insulin Resistance ◽  
Adipose Tissue ◽  
Chronic Inflammation ◽  
Metabolic Diseases ◽  
Health Concern ◽  
Noncommunicable Diseases ◽  
Adipose Tissue Inflammation ◽  
Tissue Storage ◽  
Tissue Inflammation ◽  
Increased Risk

The worldwide obesity epidemic has become a major health concern, because it contributes to higher mortality due to an increased risk for noncommunicable diseases including cardiovascular diseases, type 2 diabetes, musculoskeletal disorders and some cancers. Insulin resistance may link accumulation of adipose tissue in obesity to metabolic diseases, although the underlying mechanisms are not completely understood. In the past decades, data from human studies and transgenic animal models strongly suggested correlative, but also causative associations between activation of proinflammatory pathways and insulin resistance. Particularly chronic inflammation in adipose tissue seems to play an important role in the development of obesity-related insulin resistance. On the other hand, adipose tissue inflammation has been shown to be essential for healthy adipose tissue expansion and remodelling. However, whether adipose tissue inflammation represents a consequence or a cause of impaired insulin sensitivity remains an open question. A better understanding of the molecular pathways linking excess adipose tissue storage to chronic inflammation and insulin resistance may provide the basis for the future development of anti-inflammatory treatment strategies to improve adverse metabolic consequences of obesity. In this review, potential mechanisms of adipose tissue inflammation and how adipose tissue inflammation may cause insulin resistance are discussed.

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