The effect of γ-linolenic acid on Polycystic Ovary Syndrome associated Focal Segmental Glomerulosclerosis via TGF-ß pathway.

BACKGROUND: In recent years, female infertility from Polycystic Ovary Syndrome (PCOS) has gained scientific interest. PCOS alters the metabolic and endocrine functioning in females. The elevation in androgens can damage the androgen receptors present on the kidney giving rise to renal disorders like Focal Segmental Glomerulosclerosis (FSGS). Transforming Growth Factor Beta (TGF-ß) in the ovary is activated by activin for Follicle Stimulating Hormone (FSH) secretion and in the kidney by thrombospondin 1 (TSP1) for cell growth and apoptosis. Studies show that gamma-linolenic acid (GLA) effectively treats breast cancer, eczema, inflammatory conditions and PCOS. AIM: The study aimed to find out the possibility of FSGS development in PCOS and to understand the effect of GLA on FSGS via the TGF-ß pathway. METHOD: To carry out the study, the dehydroepiandrosterone (DHEA) induced PCOS model was used. Three groups namely vehicle control, DHEA, and DHEA+GLA, were used with six animals in each. TGF-ß1, TGF-ß2, and TSP1 genes were studied using real-time PCR. RESULTS: The study showed an increase in the level of renal fibrosis biomarker, TSP1, in the DHEA group, which was further decreased by an anti-inflammatory agent, GLA. The TGF-ß1 and TGF-ß2 genes associated with the TGF-ß pathway were seen to be increased in DHEA-induced PCOS rats which showed a possible relation between the two conditions. CONCLUSION: The study shows a possible development of renal fibrosis in the DHEA-induced PCOS model. The GLA might act as a ligand to regulate TGF-ß signaling in glomerulosclerosis in a DHEA-induced PCOS model.

Can polyunsaturated fatty acids regulate Polycystic Ovary Syndrome via TGF-ß signalling?

Polycystic Ovary Syndrome (PCOS) is a metabolic condition that affects women in their reproductive age by altering the ovarian hormone levels, leading to infertility. Increased inflammation, insulin resistance, hyperandrogenism, irregular menses, and infertility are the causes of morbidity when PCOS is the disease in question. PCOS is considered a multifactorial disease resulting from the disruption of multiple signalling pathways. Hence, the mono-targeted drugs are hardly adequate and conventional therapeutic strategies provide only palliative care. Studies show that the consumption of polyunsaturated fatty acids (PUFAs) regulates menstrual cycle, decrease testosterone and insulin levels, and improve metabolic health. This could favourably affect diabetes and infertility. In recent years, the fibrillin-3 gene has been linked to PCOS. Fibrillins along with the molecules in the extracellular matrix modulate the Transforming Growth Factor-ß (TGF-ß) signalling. So, mutations in the fibrillin-3 gene could cause TGF-ß dysregulation, which might further contribute to PCOS pathogenesis. Therefore, the current study aimed to understand whether PUFAs could manage PCOS via the TGF-ß pathway and function as a therapeutic agent for PCOS and its complications. To understand this, we have focused on the involvement of TGF-ß in PCOS pathogenesis, discussed the effect of PUFA on hormones, insulin resistance, inflammation, obesity, adiponectin, and cardiovascular conditions. Using PUFAs to target TGF-ß or its receptor molecules to modulate the TGF-ß production might function as a treatment option for PCOS. PUFA therapy could be a good alternative, supportive medication for PCOS.

Role of TGF-ß signalling in PCOS associated focal segmental glomerulosclerosis.

Research on polycystic ovarian syndrome (PCOS) remains intense due to its evolving impact on metabolism, reproduction and cardiovascular function. Changes in metabolic pathways can also significantly impact renal function including the development of Focal Segmental Glomerulosclerosis (FSGS), one of the most highly investigated renal diseases. In FSGS, scarring of the glomerulus vascular tuft damages the kidneys. Onset of FSGS may either be congenital or due to other disorders that affect the metabolism and normal kidney function. Both PCOS and FSGS appear to be associated with Transforming Growth Factor-ß (TGF-ß) signalling. Over-expression of TGF-ß may be due to the activation of the thrombospondin 1 (TSP1) gene, which increases the probability of developing renal disorders. Higher androgen levels in PCOS may also cause podocyte damage thus directly impacting development of FSGS. This article reviews the role of TGF-ß's in PCOS and FSGS and explores the inter-relationship between these two disorders.

Role of IL-6 signalling in Polycystic Ovarian Syndrome associated inflammation.

Polycystic ovarian syndrome is a major factor contributing to the increasing incidence of infertility around the world. The metabolic effects of prolonged exposure to PCOS have been well determined from previous studies and seem to be detrimental in the long run. Studies have shown a multitude of conditions like insulin resistance, obesity and cardiovascular disorders to be associated with PCOS. This makes PCOS a syndrome requiring utmost attention in terms of women's health and reproduction. Interleukin-6 is one of the many cytokines released by adipocytes from fat deposits in the body. This review focuses on the Interleukin 6 signaling pathway and the data available on inflammatory modulators due to its significance PCOS mediated inflammation. There is noteworthy evidence of elevated IL-6 concentration in PCOS subjects that has been discussed in detail. The regulation of IL-6 levels in the body is in turn, maintained by a close relation with other cytokines, especially by a key regulator, NF-κB. Being involved in a multitude of other pathological conditions like rheumatoid arthritis, cardiovascular disorders, asthma, colon cancer and many more, the role of IL-6 is also investigated in PCOS in search of a probable reason for underlying inflammatory condition. On summarizing the IL-6 signaling pathway and therapeutic exploitation of the same, we see that IL-6 targeted drugs may be an efficient way of treating PCOS associated inflammation.

γ-Linolenic acid ameliorates DHEA induced pro-inflammatory response in polycystic ovary syndrome via PPAR-γ signaling in rats.

The inflammatory responses associated with polycystic ovary syndrome (PCOS) may play a significant role in the severity of the disease. Emerging evidence report states that the polyunsaturated fatty acids are capable of ameliorating the PCOS condition. The therapeutic effects of γ-linolenic acid (GLA), an omega-6 fatty acid, in various inflammatory diseases have been reported. Yet, its role in PCOS associated inflammatory response remains unexplored. The aim of the study was to decipher the effects of GLA in PCOS and its role in the PPAR-γ pathway. In our study, female Wistar rats were stimulated with daily subcutaneous injections of DHEA (60 mg/kg per day) for 28 days to induce PCOS. Daily doses of GLA(10, 20, and 50 mg/kg) and Pioglitazone (P)(30 mg/kg) were administered orally for 14 days after PCOS induction. The levels of DHEA, leptin, PPAR-γ were measured by ELISA. The gene expression levels of leptin, TNF-α, IL-33, PPAR-γ, C/EBP-ß, SREBP-1were determined by Real Time-PCR. We observed that the GLA significantly attenuated the DHEA and leptin levels. GLA treatment also upregulated PPAR-γ expression, when compared to the DHEA group. Further, GLA treatment showed a significant reduction in DHEA induced TNF-α, IL-33, C/EBP-ß, and SREBP-1 levels in Wistar rat polycystic ovary tissue samples. The present findings could indicate that GLA is able to reduce the inflammatory response due to DHEA stimulation and thereafter potentially attenuate PCOS via the PPAR-γ pathway.