scholarly journals The Complex Interplay between Lipids, Immune System and Interleukins in Cardio-Metabolic Diseases

2018 ◽  
Vol 19 (12) ◽  
pp. 4058 ◽  
Author(s):  
Stella Bernardi ◽  
Annalisa Marcuzzi ◽  
Elisa Piscianz ◽  
Alberto Tommasini ◽  
Bruno Fabris

Lipids and inflammation regulate each other. Early studies on this topic focused on the systemic effects that the acute inflammatory response—and interleukins—had on lipid metabolism. Today, in the era of the obesity epidemic, whose primary complications are cardio-metabolic diseases, attention has moved to the effects that the nutritional environment and lipid derangements have on peripheral tissues, where lipotoxicity leads to organ damage through an imbalance of chronic inflammatory responses. After an overview of the effects that acute inflammation has on the systemic lipid metabolism, this review will describe the lipid-induced immune responses that take place in peripheral tissues and lead to chronic cardio-metabolic diseases. Moreover, the anti-inflammatory effects of lipid lowering drugs, as well as the possibility of using anti-inflammatory agents against cardio-metabolic diseases, will be discussed.

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Carla Sá ◽  
Ana Rita Oliveira ◽  
Cátia Machado ◽  
Marisa Azevedo ◽  
Cristina Pereira-Wilson

Disruptions in whole-body lipid metabolism can lead to the onset of several pathologies such as nonalcoholic fatty liver disease (NAFLD) and cardiovascular diseases (CVDs). The present study aimed at elucidating the molecular mechanisms behind the lipid-lowering effects of the flavone luteolin-7-glucoside (L7G) which we previously showed to improve plasma lipid profile in rats. L7G is abundant in plant foods of Mediterranean diet such as aromatic plants used as herbs. Results show that dietary supplementation with L7G for one week induced the expression of peroxisome proliferator-activated receptor-alpha (PPAR-α) and of its target gene carnitine palmitoyl transferase 1 (CPT-1) in rat liver. L7G showed a tendency to decrease the hepatic expression of sterol regulatory element-binding protein-1 (SREBP-1), without affecting fatty acid synthase (FAS) protein levels. Although SREBP-2 and LDLr mRNA levels did not change, the expression of HMG CoA reductase (HMGCR) was significantly repressed by L7G. L7G also inhibited this enzyme’sin vitroactivity in a dose dependent manner, but only at high and not physiologically relevant concentrations. These results add new evidence that the flavone luteolin-7-glucoside may help in preventing metabolic diseases and clarify the mechanisms underlying the beneficial health effects of diets rich in fruits and vegetables.


2017 ◽  
Vol 32 (8) ◽  
pp. 1127-1138 ◽  
Author(s):  
Sina Andalib ◽  
Pezhman Molhemazar ◽  
Hossein Danafar

Statins have been shown to exert ‘pleiotropic effects’ independent of their cholesterol lowering actions that include anti-inflammatory properties. In this study we synthesized mono methoxy poly (ethylene glycol)–poly (ε-caprolactone) (mPEG-PCL) di block copolymers. The structure of the copolymers was characterized by H nuclear magnetic resonance, Fourier-transform infrared spectroscopy, differential scanning calorimetry and gel permeation chromatography techniques. In this method, atorvastatin was encapsulated within micelles through a single-step nano-precipitation method, leading to the formation of atorvastatin-loaded mPEG-PCL (atorvastatin/mPEG-PCL) micelles. The resulting micelles were characterized further by various techniques such as dynamic light scattering and atomic force microscopy. In this study the anti-inflammatory activity of atorvastatin and atorvastatin/mPEG-PCL micelles on acute models of inflammation are analyzed, to compare the effect of indometacin in rats. Carrageenan induces rat paw edema; six animals of each group (10 groups) received indometacin, atorvastatin, and atorvastatin/mPEG-PCL micelles orally 1, 6, 12 and 24 h before carrageenan injection in paw. The paw edema thickness measured at 1, 2, 3 and 4 h after injection and percentage inhibition of edema in various groups were calculated. The results showed that the zeta potential of micelles was about −16.6 mV and the average size was 81.7 nm. Atorvastatin was encapsulated into mPEG-PCL micelles with loading capacity of 14.60 ± 0.96% and encapsulation efficiency of 62.50 ± 0.84%. Atorvastatin and atorvastatin/mPEG-PCL micelles showed significant anti-inflammatory activity in the present study. The anti-inflammatory activity of atorvastatin and atorvastatin/mPEG-PCL micelles was significant in comparison with indometacin. Atorvastatin/mPEG-PCL micelles showed more anti-inflammatory activity than atorvastatin. This study revealed the anti-inflammatory activity of atorvastatin and atorvastatin/mPEG-PCL micelles and suggested the statins have a potential inflammatory activity along with its lipid lowering properties. Contrary to anti-inflammatory effects, the pro-inflammatory responses are independent of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibition and can be mediated directly by atorvastatin.


2012 ◽  
Vol 7 (11) ◽  
pp. 1934578X1200701 ◽  
Author(s):  
Kuo-Feng Hua ◽  
Guan-Ming Chen ◽  
Chen-Lung Ho ◽  
Ming-Chung Chen ◽  
Yi-Lin Sophia Chen ◽  
...  

Recent studies demonstrated that freshwater clam (Corbicula fluminea) has lipid-lowering and hepatoprotective activities, but its effect on immune responses has not yet been addressed. Here we showed that ethanol extracts of C. fluminea (ECF) reduced nitrite oxide, interleukin-1β, interleukin-6, and tumor necrosis factor-α in lipopolysaccharide-activated macrophages. Further, ECF was fractionated into n-hexane, ethyl acetate, ethanol, and water soluble fractions. Of these, the ethyl acetate soluble fraction (EACF) had the highest capacity to inhibit pro-inflammatory mediators expression. The underlying mechanisms for the anti-inflammatory activity of EACF were demonstrated as down-regulation of ERK1/2, JNK1/2, and p38 phosphorylation and NF-κB activity. Using gas chromatography-mass spectrometric analysis EACF was found to be composed mainly of fatty acids and steroids. Our results provide evidence that freshwater clam has anti-inflammatory activity, and support the possibility for the development of freshwater clam as a health supplement or adjuvant therapeutic agent for either preventing or treating inflammation related diseases.


2021 ◽  
Vol 22 (16) ◽  
pp. 8860
Author(s):  
Nataly Sanhueza ◽  
Ricardo Fuentes ◽  
Andrea Aguilar ◽  
Beatriz Carnicero ◽  
Karina Vega ◽  
...  

Background: The communication between the brain and the immune system is a cornerstone in animal physiology. This interaction is mediated by immune factors acting in both health and pathogenesis, but it is unclear how these systems molecularly and mechanistically communicate under changing environmental conditions. Behavioural fever is a well-conserved immune response that promotes dramatic changes in gene expression patterns during ectotherms’ thermoregulatory adaptation, including those orchestrating inflammation. However, the molecular regulators activating the inflammatory reflex in ectotherms remain unidentified. Methods: We revisited behavioural fever by providing groups of fish a thermal gradient environment during infection. Our novel experimental setup created temperature ranges in which fish freely moved between different thermal gradients: (1) wide thermoregulatory range; T° = 6.4 °C; and (2) restricted thermoregulatory range; T° = 1.4 °C. The fish behaviour was investigated during 5-days post-viral infection. Blood, spleen, and brain samples were collected to determine plasmatic pro- and anti-inflammatory cytokine levels. To characterize genes’ functioning during behavioural fever, we performed a transcriptomic profiling of the fish spleen. We also measured the activity of neurotransmitters such as norepinephrine and acetylcholine in brain and peripheral tissues. Results: We describe the first set of the neural components that control inflammatory modulation during behavioural fever. We identified a neuro-immune crosstalk as a potential mechanism promoting the fine regulation of inflammation. The development of behavioural fever upon viral infection triggers a robust inflammatory response in vivo, establishing an activation threshold after infection in several organs, including the brain. Thus, temperature shifts strongly impact on neural tissue, specifically on the inflammatory reflex network activation. At the molecular level, behavioural fever causes a significant increase in cholinergic neurotransmitters and their receptors’ activity and key anti-inflammatory factors such as cytokine Il10 and Tgfβ in target tissues. Conclusion: These results reveal a cholinergic neuronal-based mechanism underlying anti-inflammatory responses under induced fever. We performed the first molecular characterization of the behavioural fever response and inflammatory reflex activation in mobile ectotherms, identifying the role of key regulators of these processes. These findings provide genetic entry points for functional studies of the neural–immune adaptation to infection and its protective relevance in ectotherm organisms.


Foods ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1569
Author(s):  
Mingyu Yin ◽  
Ryosuke Matsuoka ◽  
Yinci Xi ◽  
Xichang Wang

Perturbed lipid metabolism leads to ectopic lipid accumulation in tissues, such as the liver, thereby causing nonalcoholic fatty liver disease (NAFLD) and negatively influencing circulating lipid profile-inducing dyslipidemia. Phospholipids (PLs) with special biological activity are used to treat chronic diseases such as cardiovascular and cerebrovascular disease. PLs derived from egg yolk and soya bean have significant antioxidant and lipid-lowering abilities. This study examined the therapeutic effects of them on hyperlipidemia using a high-fructose-fed rat model; lipid metabolism and anti-inflammatory effects were also analyzed. The results showed that both egg yolk and soya bean phospholipids (EPLs and SPLs) reduced liver weight, hepatic TG, and MDA content as well as serum ALT, AST, TBA, and CRP levels (p < 0.05). The PLs also showed hypolipidemic and anti-inflammatory effects. EPLs and SPLs could inhibit the accumulation of hepatic fatty acids C18:1N9C, C18:0, and C22:6NS of rats fed a high-fat-and-sucrose diet. The intake of EPLs could significantly increase acetylcholine content in the blood and brain tissue. Histological examination showed that PLs intake could ameliorate the damage to liver tissue. This study suggested that EPLs and SPLs had a certain capacity of hypolipidemic and liver protection, and the therapeutic benefits of EPLs tended to be more effective than that of soybean phospholipids.


Neuroglia ◽  
2021 ◽  
Vol 2 (1) ◽  
pp. 89-97
Author(s):  
Satoshi Okuyama ◽  
Masafumi Matsuda ◽  
Yuna Okusako ◽  
Sanae Miyauchi ◽  
Toshiki Omasa ◽  
...  

Inflammation is the cause and/or result of many diseases in peripheral tissues and the central nervous system. Recent findings suggested that inflammation in peripheral tissue induces an inflammatory response in the brain that activates glial cells, which, in turn, induce neuronal cell dysfunction. Therefore, anti-inflammatory compounds are important for the suppression of chronic inflammation and prevention of disease. The present study revealed microglial activation in the hippocampus of the brain two days after the peripheral administration of lipopolysaccharide (LPS). Furthermore, the expression of the synaptic vesicle membrane protein, synaptophysin, in the CA3 stratum lucidum of the hippocampus was down-regulated 7 days after the LPS injection. The administration of tocotrienols, a type of vitamin E, significantly attenuated these changes in the hippocampus. Collectively, the present results demonstrated the spread of peripheral inflammatory responses to the brain, in which glial activation and neuronal dysfunction were induced, while tocotrienols exerted anti-inflammatory effects and protected neurons from damage.


Hypertension ◽  
2017 ◽  
Vol 70 (suppl_1) ◽  
Author(s):  
Venkateswara R Gogulamudi ◽  
Umadevi Subramanian ◽  
Meaghan Bloodworth ◽  
Kailash N Pandey

Disruption of natriuretic peptide receptor-A (NPRA) gene ( Npr1 ) activates the pro-inflammatory responses, which contributes to the pathogenesis of hypertension and end-organ damage. The objective of this study was to determine the kinetic responses of pro- and anti-inflammatory cytokines in Npr1 gene-knockout (KO) mice. Npr1 0-copy ( Npr1 -/- ), 1-copy ( Npr1 +/- ), and 2-copy ( Npr1 +/+ ) mice were pre-treated with rapamycin and multiplex analyses were done to assess cytokines levels. Pro-inflammatory cytokine, IFN-γ protein levels in plasma and kidney of 0-copy and 1-copy mice were markedly higher compared with 2-copy mice (76±1; 49±2 vs 32±1.3 pg/ml; 79±2; 29±1 vs. 27±0.5 pg/mg, respectively). Similarly, IL-6 levels in plasma and kidney were significantly elevated in 0-copy and 1-copy mice than 2-copy mice (52±1; 27±0.5 vs.12±0.4 pg/ml; 49±1.5; 38±2 vs.18±1.1 pg/mg, respectively). Interestingly, anti-inflammatory cytokine IL-5 protein levels in plasma and kidneys were significantly down-regulated in 0-copy and 1-copy mice than 2-copy mice (6±0.8; 5±0.1 vs. 12±0.5 pg/ml; 6±0.6; 9±0.4 vs. 28±0.5 pg/mg). IL-10 levels in plasma and kidney of 0-copy and 1-copy mice were also significantly decreased than 2-copy mice (22±0.4; 39±1 vs. 62±3 pg/ml; 14±1.7; 36±0.2 vs. 52±3 pg/mg). Rapamycin significantly reduced the levels of IFN- γ in plasma and kidney of 0-copy (50%, 35%) and 1-copy (63%, 55%) mice and IL-6 level in 0-copy (60%, 38%) and in 1-copy (40%, 26%) mice compared with 2-copy mice. In contrast, rapamycin treatment significantly elevated IL-5 levels in plasma and kidneys of 0-copy (68%, 77%) and 1-copy (61%, 64%) mice and IL-10 levels in 0-copy (80%, 78%) and 1-copy (47%, 25%) mice than 2-copy mice. A significant decrease in blood pressure occurred in rapamycin-treated 0-copy (19±4 mmHg) and 1-copy (12±3 mmHg) mice than untreated control mice. The results demonstrate that the expression of pro-inflammatory cytokines is greatly upregulated in Npr1 KO mice compared with 2-copy mice and rapamycin serves as the immune modulator of anti-inflammatory cytokines in these animals. The present findings implicate that rapamycin might act as an anti-inflammatory drug for the treatment of pathophysiology of hypertension-associated inflammation.


2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Shi Tang ◽  
Ming Wan ◽  
Wei Huang ◽  
R. C. Stanton ◽  
Yong Xu

Acute inflammatory responses are host-protective and normally self-limited; these responses can maintain cell homeostasis and promote defense against various infections and damage factors. However, when improperly managed or inappropriately activated, acute inflammation can lead to persistent and uncontrolled chronic inflammation, which is associated with many other chronic diseases including cardiovascular disease and metabolic disease. Recently, studies have shown that resolution of acute inflammation is a biosynthetically active process. Specialized proresolving lipid mediators (SPMs) known as resolvins and protectins are autacoids that resolve inflammation. A new family of anti-inflammatory and proresolving lipid mediators have recently been reported, known as maresins, which are biosynthesized from docosahexaenoic acid (DHA) by macrophages, have a conjugated double-bond system, and display strong anti-inflammatory and proresolving activity. Here, we review the biological actions, pathways, and mechanisms of maresins, which may play pivotal roles in the resolution of inflammation.


2007 ◽  
Vol 98 (09) ◽  
pp. 579-586 ◽  
Author(s):  
Alexander Cornet ◽  
Ellen Smit ◽  
Albertus Beishuizen ◽  
A. B. Johan Groeneveld

SummaryThe crosstalk between coagulation and inflammation and the propensity for microthromboembolic disease during sepsis calls for anticoagulant measures to prevent tissue hypoxygenation and to attenuate organ damage and dysfunction. Only one anticoagulant, recombinant human activated protein C (aPC, drotrecogin-α) has a proven survival benefit when used as an adjunctive therapy for human sepsis, partly because of its anti-inflammatory effect. However, heparin (-like compounds) may exert similar beneficial anti-inflammatory actions as aPC, in spite of the relatively narrow therapeutic window for anticoagulation. This narrative review is based on a Medline search of relevant basic and clinical studies published in English and discusses the potential role of heparin in modulating inflammatory responses in the treatment of animal models and human sepsis and its harmful sequelae. In any case, the results of a metaanalysis based on animal data suggest a potentially life-saving effect of heparin (-like compounds) in the treatment of sepsis.Therefore, a prospective randomized clinical trial is called upon to study effects in human sepsis.


2010 ◽  
Vol 2010 ◽  
pp. 1-10 ◽  
Author(s):  
Bolin Cai ◽  
Edwin A. Deitch ◽  
Luis Ulloa

The inflammatory responses in sepsis and hemorrhage remain a major cause of death. Clinically, it is generally accepted that shock in sepsis or hemorrhage differs in its mechanisms. However, the recognition of inflammatory cytokines as a common lethal pathway has become consent. Proinflammatory cytokines such as tumor necrosis factor (TNF) or high-mobility group box1 (HMGB1) are fanatically released and cause lethal multiorgan dysfunction. Inhibition of these cytokines can prevent the inflammatory responses and organ damage. In seeking potential anti-inflammatory strategies, we reported that ethyl pyruvate and alpha7 nicotinic acetylcholine receptor (alpha7nAChR) agonists effectively restrained cytokine production to provide therapeutic benefits in both experimental sepsis and hemorrhage. Here, we review the inflammatory responses and the anti-inflammatory strategies in experimental models of sepsis and hemorrhage, as they may have a consistent inflammatory pathway in spite of their different pathophysiological processes.


Sign in / Sign up

Export Citation Format

Share Document