scholarly journals n-3 PUFA: bioavailability and modulation of adipose tissue function

2009 ◽  
Vol 68 (4) ◽  
pp. 361-369 ◽  
Author(s):  
Jan Kopecky ◽  
Martin Rossmeisl ◽  
Pavel Flachs ◽  
Ondrej Kuda ◽  
Petr Brauner ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Insulin Signalling ◽  
Low Grade ◽  
Cardiac Events ◽  
Lifestyle Modifications ◽  
Metabolic Switch ◽  
Beneficial Effects ◽  
Glucose And Lipid Metabolism ◽  
Tissue Lipids ◽  
Amp Activated Protein Kinase

Adipose tissue has a key role in the development of metabolic syndrome (MS), which includes obesity, type 2 diabetes, dyslipidaemia, hypertension and other disorders. Systemic insulin resistance represents a major factor contributing to the development of MS in obesity. The resistance is precipitated by impaired adipose tissue glucose and lipid metabolism, linked to a low-grade inflammation of adipose tissue and secretion of pro-inflammatory adipokines. Development of MS could be delayed by lifestyle modifications, while both dietary and pharmacological interventions are required for the successful therapy of MS. The n-3 long-chain (LC) PUFA, EPA and DHA, which are abundant in marine fish, act as hypolipidaemic factors, reduce cardiac events and decrease the progression of atherosclerosis. Thus, n-3 LC PUFA represent healthy constituents of diets for patients with MS. In rodents n-3 LC PUFA prevent the development of obesity and impaired glucose tolerance. The effects of n-3 LC PUFA are mediated transcriptionally by AMP-activated protein kinase and by other mechanisms. n-3 LC PUFA activate a metabolic switch toward lipid catabolism and suppression of lipogenesis, i.e. in the liver, adipose tissue and small intestine. This metabolic switch improves dyslipidaemia and reduces ectopic deposition of lipids, resulting in improved insulin signalling. Despite a relatively low accumulation of n-3 LC PUFA in adipose tissue lipids, adipose tissue is specifically linked to the beneficial effects of n-3 LC PUFA, as indicated by (1) the prevention of adipose tissue hyperplasia and hypertrophy, (2) the induction of mitochondrial biogenesis in adipocytes, (3) the induction of adiponectin and (4) the amelioration of adipose tissue inflammation by n-3 LC PUFA.

scholarly journals Short-chain fatty acids as novel therapeutics for gestational diabetes

2020 ◽  
Vol 65 (2) ◽  
pp. 21-34
Author(s):  
Rebecca Roy ◽  
Caitlyn Nguyen-Ngo ◽  
Martha Lappas
Keyword(s):  
Insulin Resistance ◽  
Fatty Acids ◽  
Adipose Tissue ◽  
Gestational Diabetes ◽  
Insulin Signalling ◽  
Short Chain Fatty Acids ◽  
Serine Phosphorylation ◽  
Short Chain ◽  
Low Grade ◽  
Chain Fatty Acids

Gestational diabetes mellitus (GDM) affects up to 16% of pregnant women and is associated with significant long-term health detriments for the mother and her offspring. Two central features of GDM are low-grade inflammation and maternal peripheral insulin resistance, therefore therapeutics which target these may be most effective at preventing the development of GDM. Short-chain fatty acids (SCFAs), such as butyrate and propionate, are metabolites produced from the fermentation of dietary fibre by intestinal microbiota. SCFAs possess anti-inflammatory, anti-obesity and anti-diabetic properties. Therefore, this study aimed to investigate the effect of SCFAs on inflammation and insulin signalling defects in an in vitro model of GDM. Human placenta, visceral adipose tissue (VAT) and s.c. adipose tissue (SAT) were stimulated with either the pro-inflammatory cytokine TNF or bacterial product lipopolysaccharide (LPS). The SCFAs butyrate and propionate blocked TNF- and LPS-induced mRNA expression and secretion of pro-inflammatory cytokines and chemokines in placenta, VAT and SAT. Primary human cells isolated from skeletal muscle were stimulated with TNF to assess the effect of SCFAs on inflammation-induced defects in the insulin signalling pathway. Butyrate and propionate were found to reverse TNF-induced increases in IRS-1 serine phosphorylation and decreases in glucose uptake. Butyrate and propionate exerted these effects by preventing ERK activation. Taken together, these results suggest that the SCFAs may be able to improve insulin sensitivity and prevent inflammation induced by sterile or bacterial inflammation. Future in vivo studies are warranted to investigate the efficacy and safety of SCFAs in preventing insulin resistance and inflammation associated with GDM.

scholarly journals Beneficial effects of dietary restriction in type 2 diabetic rats: the role of adipokines on inflammation and insulin resistance

2010 ◽  
Vol 104 (1) ◽  
pp. 76-82 ◽  
Author(s):  
Joana Crisóstomo ◽  
Lisa Rodrigues ◽  
Paulo Matafome ◽  
Carmen Amaral ◽  
Elsa Nunes ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Skeletal Muscle ◽  
Adipose Tissue ◽  
Dietary Restriction ◽  
Insulin Signalling ◽  
Diabetic Rats ◽  
Energy Restriction ◽  
Beneficial Effects

Inflammation plays an important role in diabetes mellitus and its complications. In this context, the negative cross-talk between adipose tissue and skeletal muscle leads to disturbances in muscle cell insulin signalling and induces insulin resistance. Because several studies have shown that energy restriction brings some benefits to diabetes, the aim of the present study was to evaluate the effects of dietary restriction on systemic and skeletal muscle inflammatory biomarkers, such C-reactive protein, adipokines and cytokines, and in insulin resistance in Goto-Kakizaki rats. This is an animal model of spontaneous non-obese type 2 diabetes with strongly insulin resistance and without dyslipidaemia. Animals were maintained during 2 months of dietary restriction (50 %) and were killed at 6 months of age. Some biochemical determinations were done using ELISA and Western blot. Data from the present study demonstrate that in Goto-Kakizaki rats the dietary restriction improved insulin resistance, NEFA levels and adipokine profile and ameliorated inflammatory cytokines in skeletal muscle. These results indicate that dietary restriction in type 2 diabetes enhances adipose tissue metabolism leading to an improved skeletal muscle insulin sensitivity.

Cellular and molecular effects of n−3 polyunsaturated fatty acids on adipose tissue biology and metabolism

2008 ◽  
Vol 116 (1) ◽  
pp. 1-16 ◽  
Author(s):  
Pavel Flachs ◽  
Martin Rossmeisl ◽  
Morten Bryhn ◽  
Jan Kopecky
Keyword(s):  
Fatty Acids ◽  
Adipose Tissue ◽  
Insulin Sensitivity ◽  
Polyunsaturated Fatty Acids ◽  
Tissue Growth ◽  
Low Grade ◽  
Peroxisome Proliferator ◽  
Active Metabolites ◽  
Metabolic Switch ◽  
Obesity And Diabetes

Adipose tissue and its secreted products, adipokines, have a major role in the development of obesity-associated metabolic derangements including Type 2 diabetes. Conversely, obesity and its metabolic sequelae may be counteracted by modulating metabolism and secretory functions of adipose tissue. LC-PUFAs (long-chain polyunsaturated fatty acids) of the n−3 series, namely DHA (docosahexaenoic acid; C22:6n−3) and EPA (eicosapentaenoic acid; C20:5n−3), exert numerous beneficial effects, such as improvements in lipid metabolism and prevention of obesity and diabetes, which partially result from the metabolic action of n−3 LC-PUFAs in adipose tissue. Recent studies highlight the importance of mitochondria in adipose tissue for the maintenance of systemic insulin sensitivity. For instance, both n−3 LC-PUFAs and the antidiabetic drugs TZDs (thiazolidinediones) induce mitochondrial biogenesis and β-oxidation. The activation of this ‘metabolic switch’ in adipocytes leads to a decrease in adiposity. Both n−3 LC-PUFAs and TZDs ameliorate a low-grade inflammation of adipose tissue associated with obesity and induce changes in the pattern of secreted adipokines, resulting in improved systemic insulin sensitivity. In contrast with TZDs, which act as agonists of PPARγ (peroxisome-proliferator-activated receptor-γ) and promote differentiation of adipocytes and adipose tissue growth, n−3 LC-PUFAs affect fat cells by different mechanisms, including the transcription factors PPARα and PPARδ. Some of the effects of n−3 LC-PUFAs on adipose tissue depend on their active metabolites, especially eicosanoids. Thus treatments affecting adipose tissue by multiple mechanisms, such as combining n−3 LC-PUFAs with either caloric restriction or antidiabetic/anti-obesity drugs, should be explored.

Malonyl-CoA and AMP-activated protein kinase (AMPK): possible links between insulin resistance in muscle and early endothelial cell damage in diabetes

2003 ◽  
Vol 31 (1) ◽  
pp. 202-206 ◽  
Author(s):  
N.B. Ruderman ◽  
J.M. Cacicedo ◽  
S. Itani ◽  
N. Yagihashi ◽  
A.K. Saha ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Endothelial Cell ◽  
Protein Kinase ◽  
Insulin Signalling ◽  
Cell Damage ◽  
Nuclear Factor Κb ◽  
Beneficial Effects ◽  
Malonyl Coa ◽  
Amp Activated Protein Kinase ◽  
Acid Esterification

Based on available evidence, we would propose the following. (i) Excesses of glucose and free fatty acids cause insulin resistance in skeletal muscle and damage to the endothelial cell by a similar mechanism. (ii) Key pathogenetic events in this mechanism very likely include increased fatty acid esterification, protein kinase C activation, an increase in oxidative stress (demonstrated to date in endothelium) and alterations in the inhibitor κB kinase/nuclear factor κB system. (iii) Activation of AMP-activated protein kinase (AMPK) inhibits all of these events and enhances insulin signalling in the endothelial cell. It also enhances insulin action in muscle; however, the mechanism by which it does so has not been well studied. (iv) The reported beneficial effects of exercise and metformin on cardiovascular disease and insulin resistance in humans could be related to the fact that they activate AMPK. (v) The comparative roles of AMPK in regulating metabolism, signalling and gene expression in muscle and endothelial cells warrant further study.

scholarly journals Functional Food Targeting the Regulation of Obesity-Induced Inflammatory Responses and Pathologies

2010 ◽  
Vol 2010 ◽  
pp. 1-8 ◽  
Author(s):  
Shizuka Hirai ◽  
Nobuyuki Takahashi ◽  
Tsuyoshi Goto ◽  
Shan Lin ◽  
Taku Uemura ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Inflammatory Responses ◽  
Low Grade ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Beneficial Effects ◽  
Amino Terminal ◽  
Inflammatory State ◽  
Anti Inflammatory

Obesity is associated with a low-grade systemic chronic inflammatory state, characterized by the abnormal production of pro- and anti-inflammatory adipocytokines. It has been found that immune cells such as macrophages can infiltrate adipose tissue and are responsible for the majority of inflammatory cytokine production. Obesity-induced inflammation is considered a potential mechanism linking obesity to its related pathologies, such as insulin resistance, cardiovascular diseases, type-2 diabetes, and some immune disorders. Therefore, targeting obesity-related inflammatory components may be a useful strategy to prevent or ameliorate the development of such obesity-related diseases. It has been shown that several food components can modulate inflammatory responses in adipose tissue via various mechanisms, some of which are dependent on peroxisome proliferator-activated receptorγ(PPARγ), whereas others are independent on PPARγ, by attenuating signals of nuclear factor-κB (NF-κB) and/or c-Jun amino-terminal kinase (JNK). In this review, we introduce the beneficial effects of anti-inflammatory phytochemicals that can help prevent obesity-induced inflammatory responses and pathologies.

scholarly journals GDF15 Mediates the Metabolic Effects of PPARβ/δ by Activating AMPK

2020 ◽  
Author(s):  
David Aguilar-Recarte ◽  
Emma Barroso ◽  
Javier Pizarro-Delgado ◽  
Lucía Peña ◽  
Maria Ruart ◽  
...  
Keyword(s):  
Neutralizing Antibody ◽  
Metabolic Effects ◽  
Acid Oxidation ◽  
Peroxisome Proliferator ◽  
Ampk Activation ◽  
Peroxisome Proliferator Activated Receptor ◽  
Growth Differentiation Factor 15 ◽  
Beneficial Effects ◽  
Glucose And Lipid Metabolism ◽  
Amp Activated Protein Kinase

Abstract Peroxisome proliferator-activated receptor β/δ(PPARβ/δ) activates AMP-activated protein kinase (AMPK) and plays a crucial role in glucose and lipid metabolism. Here, we examined whether the beneficial effects of PPARβ/δ activation depended on growth differentiation factor 15 (GDF15), a stress response cytokine that regulates energy metabolism. Pharmacological PPARβ/δ activation increased GDF15 levels and ameliorated glucose intolerance, fatty acid oxidation, endoplasmic reticulum stress, inflammation and activated AMPK in HFD-fed mice, whereas these effects were abrogated by the injection of a GDF15 neutralizing antibody and in Gdf15-/- mice. The AMPK-p53 pathway was involved in the PPARβ/δ-mediated increase in GDF15, which in turn activated again AMPK. Finally, Gdf15-/- mice showed reduced AMPK activation in skeletal muscle, whereas GDF15 administration resulted in AMPK activation in this organ. Collectively, these data reveal a novel mechanism by which PPARβ/δ activation increases the levels of GDF15 via AMPK and p53, which in turn mediates the metabolic effects of PPARβ/δ by sustaining AMPK activation.

scholarly journals Adipose Tissue-Specialized Immunologic Features Might Be the Potential Therapeutic Target of Prospective Medicines for Obesity

2017 ◽  
Vol 2017 ◽  
pp. 1-8 ◽  
Author(s):  
Fan Yao ◽  
Ming Zhang ◽  
Li Chen
Keyword(s):  
Adipose Tissue ◽  
Signaling Pathways ◽  
Signaling Pathway ◽  
Drug Targets ◽  
Inflammatory Diseases ◽  
Macrophage Polarization ◽  
Notch Signaling Pathway ◽  
Low Grade ◽  
Local Inflammation ◽  
Amp Activated Protein Kinase

Excessive lipid accumulation in adipose tissue is either the source of obesity or the cause and result of chronic local inflammation, and recent studies indicate that the accumulation may induce many other specialized immunologic features with macrophages and epidemic diseases. We analyze the effective stages of immune cells in adipose tissue, including macrophage recruitment, macrophage polarization, and macrophage-like phenotype preadipocyte possession to find optimal sites as drug targets. Subsequently, some main signaling pathways are summarized in this review, including the AMP-activated protein kinase (AMPK) pathway, the JNK signaling pathway, and a novel one, the Notch signaling pathway. We illustrate all these points in order to determine the general pathogenesis of chronic low-grade local inflammation in adipose tissue and the related signaling pathways. In addition, signal-associated prospective compounds, such as berberine, are summarized and discussed with potential targets in pathogenesis. This might provide some possible thoughts and novel therapies for studying chronic inflammatory diseases, such as insulin resistance and type 2 diabetes mellitus.

scholarly journals The Beneficial Effects of Quercetin, Curcumin, and Resveratrol in Obesity

2017 ◽  
Vol 2017 ◽  
pp. 1-8 ◽  
Author(s):  
Yueshui Zhao ◽  
Bo Chen ◽  
Jing Shen ◽  
Lin Wan ◽  
Yinxin Zhu ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Low Grade ◽  
Beneficial Effects ◽  
The Past ◽  
Clinical Trial Evidence ◽  
Bioactive Phytochemicals ◽  
Treatment Of Obesity ◽  
Low Grade Inflammation ◽  
Trial Evidence ◽  
Intracellular Oxidative Stress

Over the past two decades, obesity has been one of the major public health concerns in most countries. In the search for new molecules that could be used for the treatment of obesity, good perspectives have been opened up for polyphenols, a class of natural bioactive phytochemicals. Experimental and limited clinical trial evidence supports that some polyphenols such as quercetin, curcumin, and resveratrol have potential benefit functions on obesity treatment. This brief review focuses on the main functions of the above-named polyphenols on adipose tissue. These polyphenols may play beneficial effects on adipose tissue under obese condition by alleviating intracellular oxidative stress, reducing chronic low-grade inflammation, inhibiting adipogenesis and lipogenesis, and suppressing the differentiation of preadipocytes to mature adipocytes.

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