PCOS: a Chronic Disease That Fails to Produce Adequately Specialized Pro-resolving Lipid Mediators (SPMs).

Abstract Introduction: Polycystic Ovary Syndrome (PCOS) is an endocrinologic disorder that affects 5-15 % of women of their reproductive age and is a frequent cause of infertility. Major symptoms include hyperandrogenism, ovulatory dysfunction, and often obesity and/or insulin resistance. PCOS also represents a state of chronic low-grade inflammation that is closely interlinked with the metabolic features. "Classical" pro-inflammatory lipid mediators like prostaglandins (PG), leukotrienes (LT), or thromboxanes (TX) are derived from arachidonic acid (AA) and are crucial for the initial response. Resolution processes are driven by four families of so-called specialized pro-resolving mediators (SPMs): resolvins, maresins, lipoxins, and protectins. The study aimed to establish lipid mediator profiles of PCOS patients compared to healthy women to identify differences in their resolutive and pro-inflammatory lipid parameters. Material and Methods: Fifteen female patients (18-45 years) were diagnosed with PCOS according to Rotterdam criteria, and five healthy women, as comparator group, were recruited for the study. The main outcome measures were: Pro-inflammatory lipid mediators (PG, LT, TX) and their precursor AA; SPMs (Resolvins, Maresins, Protectins, Lipoxins), their precursors EPA, DHA, DPA, and their active biosynthesis pathway intermediates (18-HEPE, 17-HDHA, 14-HDHA).Results: The level of pro-inflammatory parameters in serum was significantly higher in PCOS-affected women. The ratio [(sum of pro-inflammatory molecules) / (sum of SPMs plus hydroxylated intermediates)] reflecting the inflammatory state was significantly lower in the group of healthy women.Conclusion: There is a strong pro-inflammatory state in PCOS patients. Further research will clarify whether supplementation with SPMs or their precursors may improve this state.

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PCOS: A Chronic Disease that Fails to Produce Adequately Specialized Pro-Resolving Lipid Mediators (SPMs)

10.20944/preprints202108.0473.v1 ◽

2021 ◽

Author(s):

Pedro-Antonio Regidor ◽

Xavier de la Rosa ◽

Anna Mueller ◽

Manuela Sailer ◽

Fernando Gonzalez Santos ◽

...

Keyword(s):

Polycystic Ovary ◽

Initial Response ◽

Lipid Mediators ◽

Reproductive Age ◽

Lipid Mediator ◽

Low Grade ◽

Healthy Women ◽

Inflammatory State ◽

Inflammatory Molecules ◽

Resolution Processes

Introduction: Polycystic Ovary Syndrome (PCOS) is an endocrinologic disorder that affects 5-15 % of women of their reproductive age and is a frequent cause of infertility. Major symptoms include hyperandrogenism, ovulatory dysfunction, a characteristic multi-follicular morphology of the ovary, an elevated ratio of LH/FSH, and often obesity and/or insulin resistance. PCOS also represents a state of chronic low-grade inflammation that is closely interlinked with the metabolic features. Inflammatory processes consist of the acute inflammatory response and resolution processes initiated concomitantly. "Classical" pro-inflammatory lipid mediators like prostaglandins (PG), leukotrienes (LT), or thromboxanes (TX) are derived from arachidonic acid (AA) and are crucial for the initial response. Resolution processes are driven by four families of so-called specialized pro-resolving mediators (SPMs): resolvins, maresins, lipoxins, and protectins. SPM biosynthesis starts from the essential polyunsaturated fatty acids DHA, DPA, or EPA via certain hydroxylated intermediates (18-HEPE, 17-HDHA, 14-HDHA). The present study aimed to establish lipid mediator profiles of PCOS patients compared to healthy women to identify differences in their resolutive and pro-inflammatory lipid parameters. Material and Methods: Blood samples were taken (20 ml), separated into plasma and serum, and analyzed by HPLC/MS-QQQ. Fifteen female patients (18-45 years) were diagnosed with PCOS according to Rotterdam criteria, and five healthy women, as comparator group, were recruited for the study. The main outcome measures were: Pro-inflammatory lipid mediators (PG, LT, TX) and their precursor AA; SPMs (Resolvins, Maresins, Protectins, Lipoxins), their precursors EPA, DHA, DPA, and their active biosynthesis pathway intermediates (18-HEPE, 17-HDHA, 14-HDHA). Ratio [(sum of pro-inflammatory molecules)/sum of SPMs]. Results: The level of pro-inflammatory parameters in serum was significantly higher in PCOS-affected women. The ratio [(sum of pro-inflammatory molecules) / (sum of SPMs plus hydroxylated intermediates)] reflecting the inflammatory state was significantly lower in the group of healthy women. Conclusion: There is a strong pro-inflammatory state in PCOS patients. Further research will clarify whether supplementation with SPMs or their precursors may improve this state.

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Effect of DHT-Induced Hyperandrogenism on the Pro-Inflammatory Cytokines in a Rat Model of Polycystic Ovary Morphology

Medicina ◽

10.3390/medicina56030100 ◽

2020 ◽

Vol 56 (3) ◽

pp. 100

Author(s):

Abhaya Krishnan ◽

Sridhar Muthusami ◽

Loganayaki Periyasamy ◽

Jone A. Stanley ◽

Vasudevan Gopalakrishnan ◽

...

Keyword(s):

Inflammatory Markers ◽

Polycystic Ovary ◽

Elevated Serum ◽

Model System ◽

Reproductive Age ◽

Albino Rats ◽

Low Grade ◽

Tnf Α ◽

Inflammatory State

Background and Objectives: Polycystic ovary syndrome (PCOS) is one of the most prevalent disorders among women of reproductive age. It is considered as a pro-inflammatory state with chronic low-grade inflammation, one of the key factors contributing to the pathogenesis of this disorder. Polycystic ovary is a well-established criterion for PCOS. The present investigation aimed at finding the role of hyperandrogenism, the most important feature of PCOS, in the development of this inflammatory state. To address this problem, we adopted a model system that developed polycystic ovary morphology (PCOM), which could be most effectively used in order to study the role of non-aromatizable androgen in inflammation in PCOS. Materials and Methods: Six rats were used to induce PCOM in 21-days-old female Wistar albino rats by using a pre-determined release of dihydrotestosterone (DHT), a potent non-aromatizable androgen, achieved by implanting a DHT osmotic pump, which is designed to release a daily dose of 83 μg. Results: After 90 days, the rats displayed irregular estrous cycles and multiple ovarian cysts similar to human PCOS. Elevated serum inflammatory markers such as tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β), and the presence of a necrotic lesion in the liver, osteoclast in the femur, multinucleated giant cells and lymphocytes in the ovary based on histopathological observation of DHT-treated rats clearly indicated the onset of inflammation in the hyperandrogenic state. Our results show no significant alterations in serum hormones such as luteinizing hormone (LH), follicle stimulating hormone (FSH), insulin, and cortisol between control and hyperandrogenised rats. DHT was significantly elevated as compared to control. mRNA studies showed an increased expression level of TNF-α and IL-1β, further, the mRNA expression of urocortin 1 (Ucn-1) was stupendously elevated in the liver of hyperandrogenised rats. Conclusions: Thus, results from this study provide: (1) a good PCOM model system in order to study the inflammatory changes in PCOS aspects, (2) alteration of inflammatory markers in PCOM rats that could be either due to its direct effect or by the regulation of various inflammatory genes and markers in the liver of hyperandrogenic state suggesting the regulatory role of DHT, and (3) alteration in stress-related protein in the liver of PCOM rats.

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Inflammation and reproductive function in women with polycystic ovary syndrome

Biology of Reproduction ◽

10.1093/biolre/ioab050 ◽

2021 ◽

Author(s):

Leandro M Velez ◽

Marcus Seldin ◽

Alicia B Motta

Keyword(s):

Polycystic Ovary Syndrome ◽

Chronic Inflammation ◽

Polycystic Ovary ◽

Essential Feature ◽

Reproductive Function ◽

Cardiovascular Complications ◽

Reproductive Age ◽

Metabolic Abnormalities ◽

Ovary Syndrome ◽

Inflammatory State

Abstract Polycystic Ovary Syndrome (PCOS) is one of the most frequent endocrinopathies, affecting 5–10% of women of reproductive age, and is characterized by the presence of ovarian cysts, oligo, or anovulation, and clinical or biochemical hyperandrogenism [1]. Metabolic abnormalities such as hyperinsulinemia, insulin resistance, cardiovascular complications, dyslipidemia, and obesity are frequently present in PCOS women [1]. Several key pathogenic pathways overlap between these metabolic abnormalities, notably chronic inflammation. The observation that this mechanism was shared led to the hypothesis that a chronic inflammatory state could contribute to the pathogenesis of PCOS [2]. Moreover, while physiological inflammation is an essential feature of reproductive events such as ovulation, menstruation, implantation, and labour at term [3], the establishment of chronic inflammation may be a pivotal feature of the observed reproductive dysfunctions in PCOS women [2]. Taken together, the present work aims to review the available evidence about inflammatory mediators and related mechanisms in women with PCOS, with an emphasis on reproductive function.

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Assessment of serum adiponectin levels in women with polycystic ovary syndrome

Obsgyne Review: Journal of Obstetric and Gynecology ◽

10.17511/joog.2021.i02.01 ◽

2021 ◽

Vol 7 (2) ◽

pp. 21-27

Author(s):

Dr. Mukund B. Patel ◽

◽

Dr. Ramesh C. Patel ◽

Keyword(s):

Polycystic Ovary Syndrome ◽

Polycystic Ovary ◽

Tertiary Care ◽

Fasting Blood Glucose ◽

Hdl Cholesterol ◽

Study Groups ◽

Reproductive Age ◽

Serum Adiponectin ◽

Ovary Syndrome ◽

Healthy Women

Background and Aim: Serum adiponectin levels were found to be altered in women with polycysticovary syndrome (PCOS) due to the increased adiposity commonly observed in them. Accordingly,earlier studies have reported decreased adiponectin levels in PCOS women. the present study wasconducted to measure serum adiponectin levels in women with PCOS and to evaluate its associationwith the biochemical parameters studied.Material and Methods: The present study included 50women of reproductive age attending the department of Gynecology, tertiary care institute of Indiaand diagnosed with polycystic ovary syndrome based on Rotterdam criteria. Fifty age-matchedhealthy women were recruited as controls. t. Adiponectin levels were measured along withmeasurement of fasting blood glucose, lipid profile using commercial kits and insulin resistance(HOMA-IR) was calculated. Results: Both the study groups were matched concerning age, however,PCOS women were obese when compared to healthy women (p<0.001). Serum total cholesterol andtriglyceride levels were significantly higher (p≤0.05) and serum adiponectin concentration wassignificantly lower in PCOS women when compared to controls (p≤0.05). HDL cholesterol, fastinginsulin and HOMA-IR were similar between cases and controls. Adiponectin did not show significantassociation with any of the parameters studied (Table 2). Conclusion: Serum adiponectin levels aresignificantly lower in women with polycystic ovary syndrome compared to healthy women. Thehyperandrogenemia which is one of the characteristic features of PCOS leads to a state of adipositywhich can further cause a decrease in adiponectin levels.

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Adipose tissue dysfunction, adipokines, and low-grade chronic inflammation in polycystic ovary syndrome

Reproduction ◽

10.1530/rep-14-0435 ◽

2015 ◽

Vol 149 (5) ◽

pp. R219-R227 ◽

Cited By ~ 112

Author(s):

Poli Mara Spritzer ◽

Sheila B Lecke ◽

Fabíola Satler ◽

Debora M Morsch

Keyword(s):

Adipose Tissue ◽

Polycystic Ovary Syndrome ◽

Polycystic Ovary ◽

Lifestyle Changes ◽

Reproductive Age ◽

Sufficient Evidence ◽

Low Grade ◽

Androgen Excess ◽

Ovary Syndrome ◽

Increased Risk

Polycystic ovary syndrome (PCOS), a complex condition that affects women of reproductive age, is characterized by ovulatory dysfunction and androgen excess. Women with PCOS present higher prevalence of obesity, central adiposity, and dyslipidemia, and face increased risk of type 2 diabetes. PCOS is closely linked to functional derangements in adipose tissue. Adipocytes seem to be prone to hypertrophy when exposed to androgen excess, as experienced by women with PCOS, and both adipose tissue hypertrophy and hyperandrogenism are related to insulin resistance. Hypertrophic adipocytes are more susceptible to inflammation, apoptosis, fibrosis, and release of free fatty acids. Disturbed secretion of adipokines may also impact the pathophysiology of PCOS through their influence on metabolism and on sex steroid secretion. Chronic low-grade inflammation in PCOS is also related to hyperandrogenism and to the hypertrophy of adipocytes, causing compression phenomena in the stromal vessels, leading to adipose tissue hypoperfusion and altered secretion of cytokines. Lifestyle changes are the first-line intervention for reducing metabolic risks in PCOS and the addition of an insulin-sensitizing drug might be required. Nevertheless, there is not sufficient evidence in favor of any specific pharmacologic therapies to directly oppose inflammation. Further studies are warranted to identify an adipokine that could serve as an indirect marker of adipocyte production in PCOS, representing a reliable sign of metabolic alteration in this syndrome.

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Obesity and low-grade inflammation

10.35466/ra2021n6407 ◽

2021 ◽

Author(s):

Javier Ávila Román

Keyword(s):

Intestinal Microbiota ◽

Inflammatory Process ◽

Saturated Fat ◽

Lipid Mediators ◽

The Body ◽

Oral Glucose ◽

Low Grade ◽

Increased Risk ◽

Inflammatory State ◽

Anti Inflammatory

Obesity is a non-communicable and multifactorial disease that may have a genetic component. However, the main causes of obesity are related to poor eating habits including consumption of high amounts of saturated fat and sugar and a sedentary lifestyle. These habits can lead to pathologies associated to obesity such as overweight, hypertension and type 2 diabetes, increased cholesterol, heart and liver diseases and an increased risk of suffering some types of cancer. Furthermore, changes in the composition of the intestinal microbiota, largely defined by diet, can cause differences in nutrients bioavailability and even in their metabolization, affecting the metabolic state of the individual. Obesity leads to an increase in the basal inflammatory state due to the consumption of saturated fat. This brings the breaking of the “tight junctions” that maintain the integrity of the intestinal barrier, allowing components of the diet or the lipopolysaccharide (LPS) of the bacterial wall to reach the bloodstream, causing the activation of the immune system. In this sense, inflammation is a protective mechanism of the body that involves lipid mediators synthesis, generically called oxylipins (OXLs). OXLs can be pro-inflammatory, anti-inflammatory or pro-resolving in nature. When an inflammatory process begins, the predominant OXLs are those derived from arachidonic acid (ARA) giving rise to leukotrienes (LTs), thromboxanes (TXs) and prostaglandins (PGs). However, once an inflammation threshold is reached, lipoxins (LXs) are synthesized from LTs, which have a pro-resolutive role. Furthermore, the human body can synthesize anti-inflammatory OXLs (resolvins, maresins, protectins and lipoxins) from dietary omega-3 acids, such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). For this reason, in an obesogenic context, there is a higher basal inflammatory state than in a non-obese individual. In this context, we have carried out a study in 8-week-old male Wistar rats, fed a standard diet or cafeteria diet (CAF), which better simulates the high-fat and high-sugar diet in humans in comparison with a commercial pellet for 5 weeks. Four experimental groups were established, two groups were fed the standard diets and another two groups fed the CAF. Besides, one of each group mentioned received a cocktail of antibiotics (ABX) during the last two weeks to generate a dysbiosis of the microbiota. After this time, saphenous vein blood samples were taken for the metabolomic study of circulating lipid mediators and stool samples for intestinal microbiota determination. The model was validated by evaluating body weight gain and an oral glucose tolerance test, observing significant differences between both diets. The diversity of the microbiota was lower in those groups treated with ABX, regardless to diet. It was observed that both treatments with ABX and diet caused changes in the composition of microbiota, where ABX was the most relevant parameter. The Principal Component Analysis (PCA) study evaluates the OXLs profile that each animal shows with respect to 64 OXLs studied by metabolomics. This parameter showed a clear difference in the OXLs profile according to the diet. Correlations were made to know if there was a relationship between the composition of the microbiota and the presence of certain OXLs in blood, and it was concluded that there is a clear relationship between the changes in the microbiota and the profile of these OXLs in blood, which may explain the remarkable role of the microbiota in the inflammatory process. Furthermore, these findings may lead to the development of new obesity markers based on the OXLs profile associated with a microbiota profile. However, more studies are necessary to establish the specific action mechanisms responsible of this association.

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Chronic Low Grade Inflammation in Pathogenesis of PCOS

International Journal of Molecular Sciences ◽

10.3390/ijms22073789 ◽

2021 ◽

Vol 22 (7) ◽

pp. 3789

Author(s):

Ewa Rudnicka ◽

Katarzyna Suchta ◽

Monika Grymowicz ◽

Anna Calik-Ksepka ◽

Katarzyna Smolarczyk ◽

...

Keyword(s):

Endothelial Cell ◽

Polycystic Ovary Syndrome ◽

Chronic Inflammation ◽

Polycystic Ovary ◽

Low Grade ◽

C Reactive Protein ◽

Ovary Syndrome ◽

Gene Markers ◽

Reactive Protein ◽

Inflammatory State

Polycystic ovary syndrome (PCOS) is a one of the most common endocrine disorders, with a prevalence rate of 5–10% in reproductive aged women. It’s characterized by (1) chronic anovulation, (2) biochemical and/or clinical hyperandrogenism, and (3) polycystic ovarian morphology. PCOS has significant clinical implications and can lead to health problems related to the accumulation of adipose tissue, such as obesity, insulin resistance, metabolic syndrome, and type 2 diabetes. There is also evidence that PCOS patients are at higher risk of cardiovascular diseases, atherosclerosis, and high blood pressure. Several studies have reported the association between polycystic ovary syndrome (PCOS) and low-grade chronic inflammation. According to known data, inflammatory markers or their gene markers are higher in PCOS patients. Correlations have been found between increased levels of C-reactive protein (CRP), interleukin 18 (IL-18), tumor necrosis factor (TNF-α), interleukin 6 (IL-6), white blood cell count (WBC), monocyte chemoattractant protein-1 (MCP-1) and macrophage inflammatory protein-1α (MIP-1α) in the PCOS women compared with age- and BMI-matched controls. Women with PCOS present also elevated levels of AGEs and increased RAGE (receptor for advanced glycation end products) expression. This chronic inflammatory state is aggravating by obesity and hyperinsulinemia. There are studies describing mutual impact of hyperinsulinemia and obesity, hyperandrogenism, and inflammatory state. Endothelial cell dysfunction may be also triggered by inflammatory cytokines. Many factors involved in oxidative stress, inflammation, and thrombosis were proposed as cardiovascular risk markers showing the endothelial cell damage in PCOS. Those markers include asymmetric dimethylarginine (ADMA), C-reactive protein (CRP), homocysteine, plasminogen activator inhibitor-I (PAI-I), PAI-I activity, vascular endothelial growth factor (VEGF) etc. It was also proposed that the uterine hyperinflammatory state in polycystic ovary syndrome may be responsible for significant pregnancy complications ranging from miscarriage to placental insufficiency. In this review, we discuss the most importance evidence concerning the role of the process of chronic inflammation in pathogenesis of PCOS.

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LEPTIN LEVEL IN WOMEN OF REPRODUCTIVE AGE WITH THE SYNDROME OF THE POLYCYSTIC OVARY IN COMPARISON WITH HEALTHY WOMEN

V F Snegirev Archives of Obstetrics and Gynecology ◽

10.18821/2313-8726-2019-6-1-32-37 ◽

2019 ◽

Vol 6 (1) ◽

pp. 32-37

Author(s):

Anzhelika Yu. Beglova ◽

S. I Elgina

Keyword(s):

Metabolic Syndrome ◽

Polycystic Ovary ◽

Overweight And Obesity ◽

Reproductive Age ◽

Menstrual Disorders ◽

Women Of Reproductive Age ◽

Healthy Women ◽

Diagnostic Criterion ◽

The Relationship ◽

Ultrasound Parameters

Material and methods. The study included 200 women of reproductive age, of whom the 1st group included 100 PCOS female patients and the 2nd group included 100 healthy women examined using clinical, instrumental, laboratory, and statistical methods. Results. Metabolic syndrome was diagnosed in 38 (38.0%) PCOS women of early reproductive age, while in healthy women only in 25 (25.0%) (p = 0.102). The serum leptin content in PCOS women amounted of 13.85 ng/ml (4.15-17.6), which was not significantly different from that of healthy women - of 8.9 ng/ml (5.5-18.4) (p = 0.732). However, in women with manifestations of metabolic syndrome (overweight and obesity), the level of leptin was higher than in women without metabolic syndrome - 16.7 ng/ml (15.6-18.8) and 19.3 ng/ml (17.4-22.8) in PCOS women - 31.7 ng/ml (21.6-38.6) and 27.3 ng/ml (20.1-32.1) in healthy women (p = 0.045 and 0.604, respectively). An increase in its level correlated with an increase in BMI (p = 0.001). We found that an increase in leptin levels in PCOS women of reproductive age correlated with its main manifestations: menstrual disorders, infertility and ultrasound parameters of the ovaries, with an increase in BMI, the relationship was stronger. Conclusion. Thus, in PCOS women of reproductive age, metabolic syndrome is more often diagnosed than in healthy women. Overweight and obesity are of major importance in the formation of metabolic disorders. Increased leptin levels exacerbate metabolic manifestations, leading to impaired ovulation and fertility. The results show the need to determine the level of leptin as an additional diagnostic criterion for metabolic syndrome in PCOS cases.

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Polymorphisms of cytochrome genes in women with polycystic ovary syndrome

Fundamental and Clinical Medicine ◽

10.23946/2500-0764-2019-4-3-8-14 ◽

2019 ◽

Vol 4 (3) ◽

pp. 8-14

Author(s):

A. Yu. Beglova ◽

S. I. Yelgina ◽

N. V. Artymuk ◽

L. A. Gordeeva

Keyword(s):

Polycystic Ovary Syndrome ◽

Promoter Region ◽

Polycystic Ovary ◽

Molecular Genetic ◽

Molecular Genetic Analysis ◽

Reproductive Age ◽

Genotype Distribution ◽

Ovary Syndrome ◽

Healthy Women ◽

Meta Analyses

Aim. To study the polymorphisms of CYP11A1, CYP17A1, and CYP19A1 genes in women with polycystic ovary syndrome (PCOS) of reproductive age in comparison with women without PCOS.Materials and Methods. We consecutively recruited 94 women with polycystic ovary syndrome of reproductive age and 94 age-matched healthy women. All patients were subjected to molecular genetic analysis of pentanucleotide ((tttta)n) polymorphism at -528 position within the promoter region of the CYP11A1 gene, rs743572 polymorphism within the CYP17A1 gene, and rs2470152 polymorphism within the CYP19A1 gene. We further compared the frequencies of respective genotypes and alleles between the groups.Results. Genotype distribution of the indicated polymorphisms did not differ significantly between the groups. However, for CYP11A1 (tttta)n polymorphism, a trend to the accumulation of the alleles with a large number of (tttta)n-repeats was observed in women with polycystic ovary syndrome as compared to healthy women. The most common were VNTR genotypes with 6/6, 6/8 and 8/8 pentanucleotide repeats.Conclusion. The studied polymorphisms of cytochrome genes did not affect the risk of PCOS in the examined group of women. Our study may be useful for the further meta-analyses related to the genetic predisposition to PCOS.

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Resolution of Adipose Tissue Inflammation

The Scientific World JOURNAL ◽

10.1100/tsw.2010.77 ◽

2010 ◽

Vol 10 ◽

pp. 832-856 ◽

Cited By ~ 48

Author(s):

Ana González-Périz ◽

Joan Clària

Keyword(s):

Adipose Tissue ◽

Lipid Mediators ◽

Current Status ◽

Critical Event ◽

Low Grade ◽

Adipose Tissue Inflammation ◽

Nonalcoholic Fatty Liver ◽

Tissue Inflammation ◽

Inflammatory State ◽

Anti Inflammatory

The presence of the so-called “low-grade” inflammatory state is recognized as a critical event in adipose tissue dysfunction in obesity. This chronic “low-grade” inflammation in white adipose tissue is powerfully augmented through the infiltration of macrophages, which, together with adipocytes, perpetuate a vicious cycle of macrophage recruitment and secretion of free fatty acids and deleterious adipokines that predispose the development of obesity-related comorbidities, such as insulin resistance and nonalcoholic fatty liver disease. In the last decade, many factors have been identified that contribute to mounting uncontrolled inflammation in obese adipose tissue. Among them, bioactive lipid mediators derived from the cyclooxygenase and 5-lipoxygenase pathways, which convert the ω-6-polyunsaturated fatty acid (PUFA) arachidonic acid into potent proinflammatory eicosanoids (i.e., prostaglandins [PGs] and leukotrienes), have emerged. Interestingly, the same lipid mediators that initially trigger the inflammatory response also signal the termination of inflammation by stimulating the biosynthesis of anti-inflammatory and proresolving lipid autacoids. This review discusses the current status, characteristics, and progress in this class of “stop signals”, including the lipoxins, which were the first identified ω-6 PUFA–derived lipid mediators with potent anti-inflammatory properties; the recently described ω-3 PUFA–derived lipid mediators resolvins and protectins; and the cyclopentenone PGs of the D series. Special emphasis is given to the participation of these bioactive lipid autacoids in the resolution of adipose tissue inflammation and in preventing the development of obesity-related complications.

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