Enhancing Quality of Life and Sexual Functioning in Female Androgenetic Alopecia: Therapeutic Potential of Hair Follicle-Derived Stem Cells.

BACKGROUND: The study aimed to examine the impact of stem cell treatment on quality of life (QoL) and sexual functioning in women with androgenetic alopecia (AGA). METHODS: Twenty-three women underwent a single session of autologous cellular micrografts (ACMs). The World Health Organization Quality of Life Brief Version (WHOQOL-BREF) and Female Sexual Function Index (FSFI) were used before and after 6 months. RESULTS: The AGA severity decreased by an average of 1 point on the Ludwig scale (p = 0.004) after treatment. FSFI scores indicated sexual dysfunction in over half of the women at baseline, but they improved significantly post-treatment for arousal [median (IQR): 4.8 (1.5) vs. 5.10 (0.9); p = 0.035] and satisfaction [4.4 (1.4) vs. 4.8 (1.8); p = 0.025]. QoL scores improved after treatment in psychological health (57.96 ± 19.0 vs. 69.35 ± 14.0; p = 0.031) and environment (72.96 ± 13.4 vs. 81.09 ± 12.6; p = 0.007), but not in physical health and social relationships. No associations were found between the WHOQOL-BREF or FSFI domains versus age and AGA severity. CONCLUSIONS: AGA reduces QoL and impacts sexual functioning in women with AGA. The high treatment burden arises from the chronic and progressive nature of AGA, coupled with limited treatment effectiveness. Effective treatments for AGA, like ACM, are urgently needed to enhance patient-reported outcomes along with clinical results.

Short-Term Clinical Assessment of Treating Female Androgenetic Alopecia with Autologous Stem Cells Derived from Human Hair Follicles.

BACKGROUND: Androgenetic alopecia (AGA) is the most common form of alopecia, but treatment options are limited. This study evaluated clinical improvement in hair condition in women with AGA six months after a single injection of autologous cell micrografts (ACMs) containing hair follicle stem cells and dermal papilla cells. METHODS: Twenty-three women with clinically and dermoscopy-confirmed AGA were included. Five 2.5 mm punch biopsies were taken from the skin of each patient with the Regenera device. The cell suspension was prepared with the Rigeneracons device and then injected into the hormone-dependent hairy zone of the scalp. RESULTS: A significant improvement was observed on the visual analog scale (VAS) when comparing pre- and post-procedure photos (p < 0.001). The change in VAS scores was moderately negatively correlated with baseline ferritin concentration and positively with iron concentration. Improved outcomes were associated with higher baseline levels of sex hormone-binding globulin and 17α-hydroxyprogesterone. Neither testosterone nor DHT showed a significant correlation with VAS scores. CONCLUSIONS: The ACM procedure was shown to be both safe and effective, yielding satisfying results six months after a single treatment session. Future investigations should aim to gather evidence that enables the development of a cost-effective approach while minimizing treatment burden and costs.

Effect of Primary Versus Revisional One Anastomosis Gastric Bypass (OAGB) on Fatty Acid Profile.

INTRODUCTION: One anastomosis gastric bypass (OAGB) is one option of a revisional procedure for failed sleeve gastrectomy. Moreover, it can be used as a primary bariatric procedure, and is an effective surgery resulting in significant weight loss and the resolution or improvement of obesity-associated medical problems, accompanied by low perioperative complications. However, as with any therapy, OAGB has its limitations, including micronutrient deficiency or malnutrition. In our study, we compared the fatty acid (FA) profile in serum of patients after both primary OAGB (pOAGB) and revisional OAGB (rOAGB) to identify potential postsurgical FA alterations. METHODS: This is a retrospective study on patients with obesity who underwent OAGB procedures (pOAGB n=68; rOAGB n=17), conducted from 2016 to 2018. In blood, we analyzed a series of biochemical parameters, and in the serum, the FA profile was determined using gas chromatography-mass spectrometry. RESULTS: The percentage of excess BMI loss (% EBMIL) after pOAGB was 73.5 ± 2.47% in comparison to 45.9 ± 4.15% in the rOAGB group (p<0.001). In contrast to the lack of effect of rOAGB on most polyunsaturated FAs, in the pOAGB group, there was a decrease in eicosapentaenoic acid, and eicosatetraenoic and docosahexaenoic acid levels (p<0.001). We also found a decrease in very long-chain FAs (VLCFAs) and an increase in branched-chain FAs (BCFAs) after both types of OAGB procedure. CONCLUSIONS: Both OAGB procedures improved the profile of most FAs, leading to a decrease in VLCFAs, which are considered harmful, and an improvement in BCFAs, which are considered to be beneficial. There is a need to further investigate the possibility of n-3 polyunsaturated FA supplementation after pOAGB, due to the large decrease in these FAs after pOAGB.

Serum fatty acid profiles in breast cancer patients following treatment.

BACKGROUND: Breast cancer is associated with alterations in lipid metabolism. The treatment of breast cancer can also affect serum lipid composition. The purpose of this study was the examination of serum fatty acids (FAs) profiles in breast cancer survivors to assess if the FA levels normalize. METHODS: Serum levels of FAs were determined by gas chromatography-mass spectrometry in a group of breast cancer patients at baseline (before treatment, n = 28), at two follow-up visits at 12 months (n = 27) and 24 months (n = 19) after the breast cancer resection, and in the group of healthy controls (n = 25). Multivariate analysis was performed to assess how FA serum profile changes following treatment. RESULTS: Breast cancer patients' serum FA profiles at follow-ups did not normalize to the levels of control group. The greatest differences were found for levels of branched-chain (BCFA), odd-chain (OCFA) and polyunsaturated (PUFAs) FAs, all of which were significantly increased 12 months after the surgery. CONCLUSIONS: After treatment for breast cancer, the patients' serum FA profile differs from the profile before treatment and from controls, especially 12 months after treatment. Some changes may be beneficial - increased BCFA and OCFA levels, and improved n-6/n-3 PUFA ratio. This may reflect lifestyle changes in breast cancer survivors and have an impact on the risk of recurrence.

Fatty acid profiles in various lipid fractions in the female epidermis. Does the body site and age matter?

BACKGROUND: The epidermis forms the barrier between an organism and its external environment. Although one of the major functional elements of the epidermis is the lipid-enriched extracellular matrix, containing mainly ceramides, cholesterol (CHOL) and free fatty acids, the data are limited regarding the lipid profile in the epidermis. The aim of the study was to determine the whole profile of fatty acids (FAs) in the epidermis and to examine any dependence according to the age of the subject and the site on the epidermis. MATERIALS AND METHODS: Epidermis extracts obtained from 10 adults and 6 children were analyzed by gas chromatography-mass spectrometry. RESULTS: In total, 74 FAs in the human epidermis were identified. We observed the highest amounts of neutral lipids (including CHOL) compared to other lipid fractions in the epidermis, regardless of age. However, we detected an age-dependent content of the major lipid fractions, where the main difference was in the levels of polyunsaturated fatty acids. There were also differences in the lipid profile between various sites of the body, e.g. samples from the breast and abdomen were enriched with very long-chain fatty acids compared to the limb. CONCLUSION: Our research provides novel data concerning the lipid profile in the epidermis, gives further insight into skin biology and proves that the epidermis is a highly dynamic structure.

One-anastomosis gastric bypass modulates the serum levels of pro- and anti-inflammatory oxylipins, which may contribute to the resolution of inflammation.

BACKGROUND/OBJECTIVES: Oxylipins are polyunsaturated fatty acid derivatives involved in the regulation of various processes, including chronic inflammation, insulin resistance and hepatic steatosis. They can be synthesized in various tissues, including adipose tissue. There is some evidence that obesity is associated with the deregulation of serum oxylipin levels. The aim of this study was to evaluate the effect of bariatric surgery (one-anastomosis gastric bypass) on the serum levels of selected oxylipins and their fatty acid precursors and to verify the hypothesis that their changes after surgery can contribute to the resolution of inflammation. Moreover, we compared the oxylipin levels (prostaglandin E2, 13-HODE, maresin 1 and resolvin E1), fatty acids and the expression of enzymes that synthesize oxylipins in adipose tissue of lean controls and subjects with severe obesity. SUBJECTS/METHODS: The study included 50 patients with severe obesity that underwent bariatric surgery and 41 subjects in lean, control group. Fatty acid content was analyzed by GC-MS, oxylipin concentrations were measured with immunoenzymatic assay kits and real-time PCR analysis was used to assess mRNA levels in adipose tissue. RESULTS: Our results show increased expression of some enzymes that synthesize oxylipins in adipose tissue and alterations in the levels of oxylipins in both adipose tissue and serum of subjects with obesity. After bariatric surgery, the levels of anti-inflammatory oxylipins increased, whereas pro-inflammatory oxylipins decreased. CONCLUSIONS: In patients with obesity, the metabolism of oxylipins is deregulated in adipose tissue, and their concentrations in serum are altered. Bariatric surgery modulates the serum levels of pro- and anti-inflammatory oxylipins, which may contribute to the resolution of inflammation.

Alterations in complex lipids in tumor tissue of patients with colorectal cancer.

BACKGROUND: Accumulating evidence indicates alterations in lipid metabolism and lipid composition in neoplastic tissue. Earlier nuclear magnetic resonance studies showed that the contents of major lipid groups, such as triacylglycerols, phospholipids and cholesterol, are changed in colon cancer tissue. METHODS: In this study, a more detailed analysis of lipids in cancer and tumor adjacent tissues from colorectal cancer patients, using liquid chromatography-mass spectrometry, allowed for comparison of 199 different lipids between cancer tissue and tumor adjacent tissue using principal component analysis. RESULTS: Significant differences were found in 67 lipid compounds between the two types of tissue; many of these lipid compounds are bioactive lipids such as ceramides, lysophospholipids or sterols and can influence the development of cancer. Additionally, increased levels of phospholipids and sphingolipids were present, which are major components of the cell membrane, and increases in these lipids can lead to changes in cell membrane properties. CONCLUSIONS: This study showed that many complex lipids are significantly increased or decreased in colon cancer tissue, reflecting significant alterations in lipid metabolism. This knowledge can be used for the selection of potential molecular targets of novel anticancer strategies based on the modulation of lipid metabolism and the composition of the cell membrane in colorectal cancer cells.

The Effects of One-Anastomosis Gastric Bypass on Fatty Acids in the Serum of Patients with Morbid Obesity.

PURPOSE: Obesity is associated with alterations in serum fatty acid profiles. One-anastomosis gastric bypass is a type of bariatric surgery used in the treatment of morbid obesity. The aim of this study was to establish if, between 6 and 9 months after this procedure, the fatty acid composition in the serum of patients normalizes to values similar to the healthy, lean population. MATERIALS/METHODS: The study included 46 patients that underwent surgical treatment for obesity with one-anastomosis gastric bypass. The serum fatty acid composition was determined using gas chromatography-mass spectrometry. Principal component analysis was conducted to detect the differences between fatty acid profiles in patients pre- and post-surgery, and in 29 control nonobese subjects. RESULTS: Patients with morbid obesity were characterized by lowered levels of beneficial odd- and branched-chain fatty acids and polyunsaturated fatty acids. While the odd- and branched-chain fatty acid amounts normalized 6-9 months after bariatric treatment, the polyunsaturated fatty acid levels did not. Moreover, the total fatty acid profiles of patients pre- and post-bariatric surgery were still markedly different than those of lean, healthy controls. CONCLUSION: Following one-anastomosis gastric bypass, there are some beneficial changes in serum fatty acids in treated patients, possibly due to weight loss and dietary regimen changes. However, they may be insufficient to restore the proper levels of other fatty acids, which may need to be additionally supplemented.

Rearrangements of Blood and Tissue Fatty Acid Profile in Colorectal Cancer - Molecular Mechanism and Diagnostic Potential.

Colorectal cancer (CRC) is often diagnosed at an advanced stage due to the invasiveness of colonoscopy; thus, non-invasive CRC diagnostics are desirable. CRC is associated with lipid alterations. We aimed to verify whether fatty acid (FA) profiles in CRC patients may serve as a potential diagnostic tool for CRC diagnosis. FA profiles were assayed by GC-MS in cancer tissue, paired normal mucosa and serum from CRC patients and healthy controls. The levels of very long FAs - VLCFAs (26:0, 28:0 and 26:1) were the most highly increased FAs in cancer tissue compared to normal colon mucosa. Moreover, these FA were present in serum of CRC patients, they were absent in the serum of healthy subjects, or present in only trace amounts. To verify if cancer cells are the source of small amounts of these VLCFAs in the serum of patients we performed experiment in HT-29 CRC cells, which proved that CRC cells can produce and release VLCFAs into the blood. Most importantly, we defined a panel of FAs that may be assayed in a single analysis that definitely distinguishes CRC patients and healthy subjects, which was confirmed by PLS-DA and multivariate ROC analysis (AUC = 0.985). This study shows that selected FA panel may serve as a diagnostic marker for CRC.

Inhibitors of Fatty Acid Synthesis and Oxidation as Potential Anticancer Agents in Colorectal Cancer Treatment.

Aberrant fatty acid (FA) metabolism has long been recognized in colorectal cancer (CRC) cells. Since de novo lipogenesis is required for CRC tumour growth and survival, the inhibition of FA metabolism is a promising potential therapeutic target. Inhibition of the opposite process, ß-oxidation of FAs, has also showed promising results in many CRC models. For patients with CRC, both FA synthesis and ß-oxidation inhibitors are promising potential therapeutic options as monotherapies or as combination therapies with other anticancer agents. In this review, we discuss recent reports concerning inhibitors of FA synthesis and ß-oxidation in various CRC models. The exact mechanisms of action of the selected compounds described in this review remain unknown and require precise evaluation before the development of new successful therapies for CRC is possible.

Decreased Triacylglycerol Content and Elevated Contents of Cell Membrane Lipids in Colorectal Cancer Tissue: A Lipidomic Study.

Recent evidence suggests that lipid composition in cancer tissues may undergo multiple alterations. However, no comprehensive analysis of various lipid groups in colorectal cancer (CRC) tissue has been conducted thus far. To address the problem in question, we determined the contents of triacylglycerols (TG), an energetic substrate, various lipids necessary for cell membrane formation, among them phospholipids (phosphatidylcholine, phosphatidylethanolamine), sphingolipids (sphingomyelin) and cholesterol (free, esterified and total), and fatty acids included in complex lipids. 1H-nuclear magnetic resonance (1H-NMR) and gas chromatography-mass spectrometry (GC-MS) were used to analyze the lipid composition of colon cancer tissue and normal large intestinal mucosa from 25 patients. Compared with normal tissue, cancer tissues had significantly lower TG content, along with elevated levels of phospholipids, sphingomyelin, and cholesterol. Moreover, the content of oleic acid, the main component of TG, was decreased in cancer tissues, whereas the levels of saturated fatty acids and polyunsaturated fatty acids (PUFAs), which are principal components of polar lipids, were elevated. These lipidome rearrangements were associated with the overexpression of genes associated with fatty acid oxidation, and the synthesis of phospholipids and cholesterol. These findings suggest that reprogramming of lipid metabolism might occur in CRC tissue, with a shift towards increased utilization of TG for energy production and enhanced synthesis of membrane lipids, necessary for the rapid proliferation of cancer cells.

The Effect of a High-Fat Diet on the Fatty Acid Composition in the Hearts of Mice.

The Western diet can lead to alterations in cardiac function and increase cardiovascular risk, which can be reproduced in animal models by implementing a high-fat diet (HFD). However, the mechanism of these alterations is not fully understood and may be dependent on alterations in heart lipid composition. The aim of this study was to evaluate the effect of an HFD on the fatty acid (FA) composition of total lipids, as well as of various lipid fractions in the heart, and on heart function. C57BL/6 mice were fed an HFD or standard laboratory diet. The FA composition of chow, serum, heart and skeletal muscle tissues was measured by gas chromatography-mass spectrometry. Cardiac function was evaluated by ultrasonography. Our results showed an unexpected increase in polyunsaturated FAs (PUFAs) and a significant decrease in monounsaturated FAs (MUFAs) in the heart tissue of mice fed the HFD. For comparison, no such effects were observed in skeletal muscle or serum samples. Furthermore, we found that the largest increase in PUFAs was in the sphingolipid fraction, whereas the largest decrease in MUFAs was in the phospholipid and sphingomyelin fractions. The hearts of mice fed an HFD had an increased content of triacylglycerols. Moreover, the HFD treatment altered aortic flow pattern. We did not find significant changes in heart mass or oxidative stress markers between mice fed the HFD and standard diet. The above results suggest that alterations in FA composition in the heart may contribute to deterioration of heart function. A possible mechanism of this phenomenon is the alteration of sphingolipids and phospholipids in the fatty acid profile, which may change the physical properties of these lipids. Since phospho- and sphingolipids are the major components of cell membranes, alterations in their structures in heart cells can result in changes in cell membrane properties.

Correction to: The effect of western diet on mice brain lipid composition.

[This corrects the article DOI: 10.1186/s12986-019-0401-4.].

Preferential uptake of polyunsaturated fatty acids by colorectal cancer cells.

Although a growing body of evidence suggests that colorectal cancer (CRC) is associated with alterations of fatty acid (FA) profiles in serum and tumor tissues, available data about polyunsaturated fatty acid (PUFA) content in CRC patients are inconclusive. Our study showed that CRC tissues contained more PUFAs than normal large intestinal mucosa. However, serum levels of PUFAs in CRC patients were lower than in healthy controls. To explain the mechanism of PUFA alterations in CRC, we measured FA uptake by the colon cancer cells and normal colon cells. The levels of PUFAs in colon cancer cell culture medium decreased significantly with incubation time, while no changes were observed in the medium in which normal colon cells were incubated. Our findings suggest that the alterations in tumor and serum PUFA profiles result from preferential uptake of these FAs by cancer cells; indeed, PUFAs are essential for formation of cell membrane phospholipids during rapid proliferation of cancer cells. This observation puts into question potential benefits of PUFA supplementation in CRC patients.

Short-Term Effect of One-Anastomosis Gastric Bypass on Essential Fatty Acids in the Serum of Obese Patients.

One-anastomosis gastric bypass is a promising type of bariatric surgery, but it may lead to a deficiency in important nutrients, such as fatty acids. The short-term effects of one-anastomosis gastric bypass on serum fatty acids have not been studied thus far. Therefore, the aim of this study was to determine the effect of one-anastomosis gastric bypass on serum fatty acid composition two weeks after surgery. This study included 38 patients who underwent one-anastomosis gastric bypass as surgical treatment for morbid obesity. Serum fatty acid composition was analyzed before and two weeks after surgery using gas chromatography-mass spectrometry. We observed a decrease in essential polyunsaturated fatty acids (p < 0.001 for linolenic acid and p < 0.001 for linoleic acid) and odd-chain fatty acids (p = 0.004) in the serum of obese patients shortly after a one-anastomosis gastric bypass. Considering the benefits of the aforementioned fatty acids for human health, the implementation of a fatty-acid-rich diet or the use of supplementation may be recommended for patients immediately after one-anastomosis gastric bypass.

Methods of the Analysis of Oxylipins in Biological Samples.

Oxylipins are derivatives of polyunsaturated fatty acids and due to their important and diverse functions in the body, they have become a popular subject of studies. The main challenge for researchers is their low stability and often very low concentration in samples. Therefore, in recent years there have been developments in the extraction and analysis methods of oxylipins. New approaches in extraction methods were described in our previous review. In turn, the old analysis methods have been replaced by new approaches based on mass spectrometry (MS) coupled with liquid chromatography (LC) and gas chromatography (GC), and the best of these methods allow hundreds of oxylipins to be quantitatively identified. This review presents comparative and comprehensive information on the progress of various methods used by various authors to achieve the best results in the analysis of oxylipins in biological samples.

The Effect of One Anastomosis Gastric Bypass on Branched-Chain Fatty Acid and Branched-Chain Amino Acid Metabolism in Subjects with Morbid Obesity.

BACKGROUND: Subjects with morbid obesity have low levels of serum branched-chain fatty acids (BCFAs), which correlate inversely with insulin resistance, hypertriglyceridemia, and inflammation. Recent evidence suggests BCFAs are produced during branched-chain amino acid (BCAA) catabolism in human adipose tissue. Elevated concentrations of BCAAs are associated with insulin resistance. OBJECTIVES: In this single-center study, we evaluated the effect of one anastomosis gastric bypass (OAGB) on circulating BCFA and BCAA. Moreover, we determined the expression of genes involved in BCAA catabolism in adipose tissue of patients with obesity and lean controls. METHODS: Fasting levels of BCFAs and BCAAs were determined by gas and liquid chromatography, respectively, coupled with mass spectrometry, in 50 patients with morbid obesity before and 6-9 months after surgery, and in 32 lean controls. Visceral and subcutaneous adipose tissue (VAT and SAT, respectively) biopsies were collected at baseline to determine mRNA levels for enzymes involved in BCAA catabolism. RESULTS: Before surgery, patients with obesity had lower BCFAs and greater BCAAs than control subjects. OAGB increased BCFA and decreased BCAA levels. Insulin resistance (assessed by HOMA) correlated inversely with BCFAs and positively with BCAAs. Expression of genes involved in BCAA catabolism in VAT (but not SAT) was lower in patients with obesity than in lean controls. CONCLUSIONS: OAGB-induced weight loss increases circulating BCFAs and decreases circulating BCAAs in patients with morbid obesity, perhaps by altering BCAA catabolism in VAT. We speculate that this shift may be related to the improvement in insulin sensitivity after surgery.

The effect of western diet on mice brain lipid composition.

BACKGROUND: The appropriate fatty acids composition of brain lipids is critical for functioning of this organ. The alterations of brain fatty acids composition may lead to neurological and neurodegenerative diseases. METHODS: The aim of this work was to evaluate the effect of western diet containing high fat content on fatty acid composition of brain lipids. In this study we used mice fed high fat diet (HFD) for 19 weeks. Brain lipids were separated by SPE extraction and fatty acid composition in chow, mice serum, brain and other tissues was analyzed by GC-MS method. RESULTS: The body weight and adipose tissue weigh of mice after HFD increased significantly. The concentrations of most of fatty acids in serum of mice after HFD increased, due to their higher delivery from food. Unexpectedly the serum eicosapentaenoic acid (EPA) concentration was lower in mice after HFD than in controls. Also the brain, and other tissue EPA content was lower. Among studied groups of brain lipids EPA was significantly decreased in phospholipids and sphingolipids. CONCLUSIONS: Considering important role of brain EPA including maintaining of appropriate composition of cell membrane lipids and anti-inflammatory properties we conclude that decrease of brain EPA after western diet may result in impaired brain function.

In Vivo Effectiveness of Orlistat in the Suppression of Human Colorectal Cancer Cell Proliferation.

BACKGROUND/AIM: Fatty acid synthase (FASN) provides palmitate for cell membrane formation in colorectal cancer (CRC) cells, however, palmitate is also available in the blood of CRC patients. The aim of this study was to examine whether orlistat, a FASN inhibitor, is able to attenuate CRC cell growth despite the availability of extracellular palmitate. MATERIALS AND METHODS: Palmitate concentrations were measured in serum from CRC patients and healthy controls. HT-29 CRC cells were treated with orlistat and palmitate. RESULTS: Treatment of CRC cells with orlistat caused a dose-dependent inhibition of cell proliferation. In turn, delivery of extracellular palmitate at doses lower than those found in the serum of CRC patients reversed inhibition by orlistat concentrations of up to 10 µM. CONCLUSION: Inhibition of CRC cell proliferation by orlistat is reversed by palmitate which is present at high levels in the serum. Therefore, orlistat may be effective in vivo only at high concentrations.