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Lipids in Health and Disease May 2024Cancer-associated cachexia (CAC) arises from malignant tumors and leads to a debilitating wasting syndrome. In the pathophysiology of CAC, the depletion of fat plays an...
BACKGROUND
Cancer-associated cachexia (CAC) arises from malignant tumors and leads to a debilitating wasting syndrome. In the pathophysiology of CAC, the depletion of fat plays an important role. The mechanisms of CAC-induced fat loss include the enhancement of lipolysis, inhibition of lipogenesis, and browning of white adipose tissue (WAT). However, few lipid-metabolic enzymes have been reported to be involved in CAC. This study hypothesized that ELOVL6, a critical enzyme for the elongation of fatty acids, may be involved in fat loss in CAC.
METHODS
Transcriptome sequencing technology was used to identify CAC-related genes in the WAT of a CAC rodent model. Then, the expression level of ELOVL6 and the fatty acid composition were analyzed in a large clinical sample. Elovl6 was knocked down by siRNA in 3T3-L1 mouse preadipocytes to compare with wild-type 3T3-L1 cells treated with tumor cell conditioned medium.
RESULTS
In the WAT of patients with CAC, a significant decrease in the expression of ELOVL6 was found, which was linearly correlated with the extent of body mass reduction. Gas chromatographic analysis revealed an increase in palmitic acid (C16:0) and a decrease in linoleic acid (C18:2n-6) in these tissue samples. After treatment with tumor cell-conditioned medium, 3T3-L1 mouse preadipocytes showed a decrease in Elovl6 expression, and Elovl6-knockdown cells exhibited a reduction in preadipocyte differentiation and lipogenesis. Similarly, the knockdown of Elovl6 in 3T3-L1 cells resulted in a significant increase in palmitic acid (C16:0) and a marked decrease in oleic acid (C18:1n-9) content.
CONCLUSION
Overall, the expression of ELOVL6 was decreased in the WAT of CAC patients. Decreased expression of ELOVL6 might induce fat loss in CAC patients by potentially altering the fatty acid composition of adipocytes. These findings suggest that ELOVL6 may be used as a valuable biomarker for the early diagnosis of CAC and may hold promise as a target for future therapies.
Topics: Fatty Acid Elongases; Animals; Cachexia; Mice; Adipose Tissue, White; Humans; 3T3-L1 Cells; Neoplasms; Male; Female; Palmitic Acid; Lipogenesis; Middle Aged; Fatty Acids
PubMed: 38760797
DOI: 10.1186/s12944-024-02126-9 -
Animal Reproduction 2024As a positional and geometrical isomer of linoleic acid, trans 10, cis 12 conjugated linoleic acid (t10c12-CLA) reduces white fat by reducing food intake, modulating...
As a positional and geometrical isomer of linoleic acid, trans 10, cis 12 conjugated linoleic acid (t10c12-CLA) reduces white fat by reducing food intake, modulating lipid metabolism, and stimulating energy expenditure. However, the t10c12-CLA products are mostly mixtures, making it difficult to obtain accurate results. Studies are needed to investigate the effects of pure t10c12-CLA on animals and humans. In this study, we used the biallelic transgenic (tg) mice, which could produce t10c12-CLA itself, to investigate the effects of pure t10c12-CLA on female reproductive ability. The results showed that the body and relative ovary weights had no significant difference between tg and wild-type (wt) littermates at ages 3 or 10 weeks. While the fecundity test found that tg mice had a significantly longer first litter time (32.0 ± 4.70 days vs. 21.3 ± 2.31 days, <0.05), and a significantly lower number of litters (4.75 ± 2.75 vs. 6.67 ± 0.57, <0.05) when compared with wt mice during continuous mating within seven months. Hormone profiles showed that serum estradiol levels did not change in tg mice; however, significantly (<0.05) decreased progesterone and increased prostaglandin E2 levels were observed in tg mice compared with those of wt mice. Hematoxylin-eosin staining showed no pathological characteristics in tg ovaries, except for the increased atresia follicles (<0.05). Moreover, the tg mice had a significantly more extended diestrus period than the wt mice (48.4 ± 6.38% vs. 39.6 ± 3.81%, <0.05). In summary, t10c12-CLA could affect serum progesterone and prostaglandin E2 levels, lead to a disordered estrus cycle, and impact the reproductive performance of female mice. This study provided theoretical and biosafety recommendations for applying t10c12-CLA in female mammals.
PubMed: 38756621
DOI: 10.1590/1984-3143-AR2024-0010 -
Heliyon May 2024Fresh vegetables have high water content and low acidity, so drying can extend shelf life, allowing the obtaining of alternative flours for the development of new...
Fresh vegetables have high water content and low acidity, so drying can extend shelf life, allowing the obtaining of alternative flours for the development of new products. The study aimed to investigate the influence of the melon harvest and off-season on the chemical composition of melon (Cantaloupe, Charentais e Honey Dew) flours and the potential application in products. The flours were evaluated for granulometry, morphology, centesimal composition, lipid and mineral content, total phenolic compound (TPC), antioxidant activity, and technological properties. Cakes containing melon flour were produced to replace wheat flour (0, 25, and 50 %) and evaluated for proximate composition, microbiology, and sensory parameters. Flours were classified as fine-grained (MESH >16), except Charentais off-season (medium - MESH 8-16, and fine-grained - MESH >16), and all presented a rough surface and minimal cell wall ruptures. The harvest homogeneously influenced the humidity, as all the off-season flours showed higher levels [17-22 %] (p < 0.05) due to weather conditions. For TPC, Cantaloupe melon flours from the harvest (CFH) [208 mg/100 g] and off-season [877 mg/100 g] stood out (p < 0.05), and the latter showed greater antioxidant potential [328 μmol TE/g]. Palmitic, linoleic, and linolenic acid stood out in all flours, and potassium for minerals (63-78 %) in the harvest and off-season. The harvest and off-season specifically influenced the flour of each variety in swelling power, water solubility, oil absorption, and emulsifying capacity. For cakes with CFH, no thermotolerant coliforms and were detected, and the mesophilic count was <1.0 CFU/g. The ash, protein, lipid, and fiber contents increased proportionally to melon flour addition (p < 0.05). Sensory acceptance was high for cakes containing 25 and 50 % of CFH [82.78 % and 82.53 %], and most consumers would likely buy the products (4.04 and 3.99) (p < 0.05). The study contributed to knowledge about the seasonality effect and demonstrated the potential use of melon flour in developing new products.
PubMed: 38756580
DOI: 10.1016/j.heliyon.2024.e29609 -
Animal Bioscience May 2024Lactic acid (LA) treatment of cereals is known to improve ruminant performance. However, changes in cereal nutrient levels and variations in rumen fermentation remain...
OBJECTIVE
Lactic acid (LA) treatment of cereals is known to improve ruminant performance. However, changes in cereal nutrient levels and variations in rumen fermentation remain unclear.
METHOD
This study was designed to compare the effects of 5% LA treatment on the trophic and morphological characteristics of barley and to discover the differences in rumen fermentation characteristics and metabolomes between LA-treated and untreated barley.
RESULTS
Compared with those of untreated barley (BA), the dry matter (DM), crude protein (CP), ash and water-soluble carbohydrate contents of barley plants treated with 5% LA for 48 h (BALA) decreased, but the resistant starch (RS) and non-fiber carbohydrate contents increased. Moreover, the amount of proteinaceous matrix in BA decreased in response to LA treatment. During in vitro fermentation, BALA had a greater pH but lower dry matter disappearance and ammonia, methane, and short-chain fatty acid levels than BA. The differential metabolites between BA and BALA were clustered into metabolic pathways such as purine metabolism, lysine degradation, and linoleic acid metabolism. Observable differences in ultrastructure between BALA and BA were noted during fermentation.
CONCLUSION
Lactic treatment altered barley nutrient content, including DM, CP, RS, ash, water-soluble carbohydrates and non-fiber carbohydrates, and affected barley ultrastructure. These variations led to significant and incubation time-dependent changes in the in vitro fermentation characteristics and metabolome.
PubMed: 38754844
DOI: 10.5713/ab.23.0550 -
BioRxiv : the Preprint Server For... Apr 2024Barth syndrome (BTHS) is a rare mitochondrial disease caused by pathogenic variants in the gene TAFAZZIN, which leads to abnormal cardiolipin (CL) metabolism on the...
Barth syndrome (BTHS) is a rare mitochondrial disease caused by pathogenic variants in the gene TAFAZZIN, which leads to abnormal cardiolipin (CL) metabolism on the inner mitochondrial membrane. Although is ubiquitously expressed, BTHS involves a complex combination of tissue specific phenotypes including cardiomyopathy, neutropenia, skeletal myopathy, and growth delays, with a relatively minimal neurological burden. To understand both the developmental and functional effects of TAZ-deficiency in different tissues, we generated isogenic TAZ knockout (TAZ- KO) and WT cardiomyocytes (CMs) and neural progenitor cells (NPCs) from CRISPR-edited induced pluripotent stem cells (iPSCs). In TAZ-KO CMs we discovered evidence of dysregulated mitophagy including dysmorphic mitochondria and mitochondrial cristae, differential expression of key autophagy-associated genes, and an inability of TAZ-deficient CMs to properly initiate stress-induced mitophagy. In TAZ-deficient NPCs we identified novel phenotypes including a reduction in CIV abundance and CIV activity in the CIII2&CIV2 intermediate complex. Interestingly, while CL acyl chain manipulation was unable to alter mitophagy defects in TAZ-KO CMs, we found that linoleic acid or oleic acid supplementation was able to partially restore CIV abundance in TAZ-deficient NPCs. Taken together, our results have implications for understanding the tissue-specific pathology of BTHS and potential for tissue-specific therapeutic targeting. Moreover, our results highlight an emerging role for mitophagy in the cardiac pathophysiology of BTHS and reveal a potential neuron-specific bioenergetic phenotype.
PubMed: 38746168
DOI: 10.1101/2024.04.28.591534 -
Evidence-based Complementary and... 2024This study was conducted to isolate and identify the chemical compounds from the roots of (L.) and evaluate their antioxidant and antibacterial activities. From the...
This study was conducted to isolate and identify the chemical compounds from the roots of (L.) and evaluate their antioxidant and antibacterial activities. From the acetone (99.5%) extract of the roots of this plant, four anthraquinones, such as chrysophanol (), asphodeline (), aloesaponarin I (), and laccaic acid D-methyl ester (), and a new catechol derivative, 5-allyl-3-methoxybenzene-1,2-diol (), were isolated and elucidated by different chromatographic and spectroscopic methods together with linoleic acid (), respectively. Compounds , and were reported here for the first time from this plant and compound from the genus . The compounds were evaluated for their antioxidant activity using HO and DPPH assays and bactericidal activity against and . Compounds and showed highest antioxidant activities with IC values of 19.38 ± 0.64 and 32.81 ± 0.78 g/mL in DPPH, and 28.52 ± 1.08 and 27.31 ± 1.46 g/mL in HO, respectively. The isolated compounds also demonstrated considerable activity towards . Among these compounds, compound exhibited the highest activity (91.20 ± 0.12% and 9.14 ± 0.93 mm at 1.0 mg/mL) against this bacterium. The overall results suggest that the isolated compounds may be considered as potential sources of the bioactive agents to be used in the pharmacological, food, and other industries. Moreover, their high sensitivity against may also support the use of plant in the traditional medicine to treat wounds. Therefore, the isolated compounds are responsible for medicinal properties of this plant.
PubMed: 38746073
DOI: 10.1155/2024/6651648 -
Frontiers in Microbiology 2024The effects of fructo-oligosaccharides (FOS) on atopic dermatitis (AD) have not been determined.
INTRODUCTION
The effects of fructo-oligosaccharides (FOS) on atopic dermatitis (AD) have not been determined.
METHODS
In a randomized, double-blind, placebo-controlled trial, children with AD aged 24 months to 17 years received either advanced FOS containing 4.25 g of 1-kestose or a placebo (maltose) for 12 weeks.
RESULTS
The SCORAD and itching scores were reduced in patients treated with both FOS (all < 0.01) and maltose ( < 0.05 and < 0.01). Sleep disturbance was improved only in the FOS group ( < 0.01). The FOS group revealed a decreased proportion of linoleic acid (18:2) esterified omega-hydroxy-ceramides (EOS-CERs) with amide-linked shorter chain fatty acids (C28 and C30, all < 0.05), along with an increased proportion of EOS-CERs with longer chain fatty acids (C32, < 0.01).
DISCUSSION
FOS may be beneficial in alleviating itching and sleep disturbance, as well as improving skin barrier function in children with AD.
PubMed: 38741747
DOI: 10.3389/fmicb.2024.1383779 -
Ketogenic Diet Protects from Experimental Colitis in a Mouse Model Regardless of Dietary Fat Source.Nutrients Apr 2024While ketogenic diets (KDs) may have potential as adjunct treatments for gastrointestinal diseases, there is little knowledge on how the fat source of these diets...
While ketogenic diets (KDs) may have potential as adjunct treatments for gastrointestinal diseases, there is little knowledge on how the fat source of these diets impacts intestinal health. The objective of this study was to investigate how the source of dietary fat of KD influences experimental colitis. We fed nine-week-old male C57BL/6J mice ( = 36) with a low-fat control diet or KD high either in saturated fatty acids (SFA-KD) or polyunsaturated linoleic acid (LA-KD) for four weeks and then induced colitis with dextran sodium sulfate (DSS). To compare the diets, we analyzed macroscopic and histological changes in the colon, intestinal permeability to fluorescein isothiocyanate-dextran (FITC-dextran), and the colonic expression of tight junction proteins and inflammatory markers. While the effects were more pronounced with LA-KD, both KDs markedly alleviated DSS-induced histological lesions. LA-KD prevented inflammation-related weight loss and the shortening of the colon, as well as preserved and expression at a healthy level. Despite no significant between-group differences in permeability to FITC-dextran, LA-KD mitigated changes in tight junction protein expression. Thus, KDs may have preventive potential against intestinal inflammation, with the level of the effect being dependent on the dietary fat source.
Topics: Animals; Diet, Ketogenic; Colitis; Male; Mice, Inbred C57BL; Disease Models, Animal; Dextran Sulfate; Mice; Dietary Fats; Colon; Permeability; Tight Junction Proteins; Interleukin-1beta; Intestinal Mucosa; Tumor Necrosis Factor-alpha; Fatty Acids; Dextrans; Fluorescein-5-isothiocyanate
PubMed: 38732595
DOI: 10.3390/nu16091348 -
Nutrients Apr 2024Polyunsaturated fatty acids (PUFAs) can alter adipose tissue function; however, the relative effects of plant and marine n3-PUFAs are less clear. Our objective was to...
Differential Modulation by Eicosapentaenoic Acid (EPA) and Docosahexaenoic Acid (DHA) of Mesenteric Fat and Macrophages and T Cells in Adipose Tissue of Obese / Zucker Rats.
Polyunsaturated fatty acids (PUFAs) can alter adipose tissue function; however, the relative effects of plant and marine n3-PUFAs are less clear. Our objective was to directly compare the n3-PUFAs, plant-based α-linolenic acid (ALA) in flaxseed oil, and marine-based eicosapentaenoic acid (EPA) or docosahexaenoic acid (DHA) in high-purity oils versus n6-PUFA containing linoleic acid (LA) for their effects on the adipose tissue and oral glucose tolerance of obese rats. Male / Zucker rats were assigned to faALA, faEPA, faDHA, and faLA groups and compared to baseline / rats (faBASE) and lean Zucker rats (lnLA). After 8 weeks, faEPA and faDHA had 11-14% lower body weight than faLA. The oral glucose tolerance and total body fat were unchanged, but faEPA had less mesenteric fat. faEPA and faDHA had fewer large adipocytes compared to faLA and faALA. EPA reduced macrophages in the adipose tissue of / rats compared to ALA and DHA, while faLA had the greatest macrophage infiltration. DHA decreased (~10-fold) T-cell infiltration compared to faBASE and faEPA, whereas faALA and faLA had an ~40% increase. The n3-PUFA diets attenuated tumour necrosis factor-α in adipose tissue compared to faBASE, while it was increased by LA in both genotypes. In conclusion, EPA and DHA target different aspects of inflammation in adipose tissue.
Topics: Animals; Rats, Zucker; Eicosapentaenoic Acid; Docosahexaenoic Acids; Obesity; Male; Macrophages; Adipose Tissue; Rats; T-Lymphocytes; alpha-Linolenic Acid; Mesentery
PubMed: 38732558
DOI: 10.3390/nu16091311 -
International Journal of Molecular... Apr 2024Linoleic acid (LA), an n-6 polyunsaturated fatty acid (PUFA), is obtained from the maternal diet during pregnancy, and is essential for normal fetal growth and...
Linoleic acid (LA), an n-6 polyunsaturated fatty acid (PUFA), is obtained from the maternal diet during pregnancy, and is essential for normal fetal growth and development. A maternal high-LA (HLA) diet alters maternal and offspring fatty acids, maternal leptin and male/female ratio at embryonic (E) day 20 (E20). We investigated the effects of an HLA diet on embryonic offspring renal branching morphogenesis, leptin signalling, megalin signalling and angiogenesis gene expression. Female Wistar Kyoto rats were fed low-LA (LLA; 1.44% energy from LA) or high-LA (HLA; 6.21% energy from LA) diets during pregnancy and gestation/lactation. Offspring were sacrificed and mRNA from kidneys was analysed by real-time PCR. Maternal HLA decreased the targets involved in branching morphogenesis and in offspring, independent of sex. Furthermore, downstream targets of megalin, namely , and , were reduced in offspring from mothers consuming an HLA diet, independent of sex. There was a trend of an increase in the branching morphogenesis target in females ( = 0.0517). These findings suggest that an HLA diet during pregnancy may lead to altered renal function in offspring. Future research should investigate the effects an HLA diet has on offspring kidney function in adolescence and adulthood.
Topics: Animals; Female; Pregnancy; TOR Serine-Threonine Kinases; Kidney; Rats; Proto-Oncogene Proteins c-akt; Signal Transduction; Morphogenesis; Linoleic Acid; Male; Rats, Inbred WKY; Gene Expression Regulation, Developmental; Fetus
PubMed: 38731907
DOI: 10.3390/ijms25094688