acyl-CoA Oxidase Research Articles

Intermittent cold stimulation acclimates broilers to acute cold stress by affecting cardiac lipid metabolism.

This study aimed to investigate whether intermittent cold stimulation can induce adaptation in broilers to acute cold stress (ACS) by regulating the lipid metabolism of hearts. CS0 were kept at normal rearing temperature, while CS3 and CS5 were exposed to 3°C for 3 and 5 hours, respectively, on alternate days lower than CS0 from 15d to 35d. On 50d, broilers in three groups were exposed to ACS at 10°C for 12 hours (Y12). The levels of corticosterone (CORT) and liothyronine (T3), mRNA and protein levels of heart AMP-activated protein kinase/mammalian target of rapamycin (AMPK/mTOR) pathway genes were assessed at 36d, 50d and Y12. At 36d, mRNA levels of AMPKα, acyl-CoA oxidase (ACO), mTOR, sterol-regulatory element binding protein (SREBP), stearoyl-coA desaturase (SCD), acetyl-coA carboxylase (ACC), fatty acid synthase (FAS) and protein level of peroxisome proliferators-activated receptor α (PPARα) in CS3 and CS5 were significantly lower than those in CS0 (p<0.05). At 50d, compared to CS0, mRNA levels of PPARα, carnitine palmitoyltransferase1 (CPT1), ACO, tuberous sclerosis complex (TSC), SREBP and SCD, as well as protein levels of p-AMPKα/AMPKα, PPARα and SREBP were significantly increased in CS5 (p<0.05). At Y12, the levels of T3 in CS3 and CS5 were significantly higher than those in CS0 (p<0.05), mRNA levels of CPT1, ACO, SREBP, SCD and protein levels of p-AMPKα/AMPKα, SREBP, and FAS were significantly higher in CS5 than in CS0 and CS3 (p<0.05). However, compared to 50d, at Y12, mRNA levels of AMPKα, CPT1 and ACO in CS3 and CS5 significantly decreased (p<0.05), while protein levels of p-AMPKα/AMPKα significantly increased (p<0.05). This study suggested that intermittent cold stimulation at 3°C lower than normal rearing temperature for 5h could help broilers adapt to the ACS by promoting heart lipid metabolism.

(E)-5-hydroxy-7-methoxy-3-(2-hydroxybenzyl)-4-chromanone, a Major Homoisoflavonoid, Attenuates Free Fatty Acid-Induced Hepatic Steatosis by Activating AMPK and PPARα Pathways in HepG2 Cells.

(E)-5-hydroxy-7-methoxy-3-(2-hydroxybenzyl)-4-chromanone (HMC), a homoisoflavonoid isolated from Portulaca oleracea, has significant anti-adipogenesis potential; it regulates adipogenic transcription factors. However, whether HMC improves hepatic steatosis in hepatocytes remains vague. This study investigated whether HMC ameliorates hepatic steatosis in free fatty acid-treated human hepatocellular carcinoma (HepG2) cells, and if so, its mechanism of action was analyzed. Hepatic steatosis was induced by a free fatty acid mixture in HepG2 cells. Thereafter, different HMC concentrations (10, 30, and 50 µM) or fenofibrate (10 µM, a PPARα agonist, positive control) was treated in HepG2 cells. HMC markedly decreased lipid accumulation and triglyceride content in free fatty acid-treated HepG2 cell; it (10 and 50 μM) markedly upregulated protein expressions of pAMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase. HMC (10 and 50 μM) markedly inhibited the expression of sterol regulatory element-binding protein-1c, fatty acid synthase, and stearoyl-coA desaturase 1, which are the enzymes involved in lipid synthesis. Furthermore, HMC (10 and 50 μM) markedly upregulated the protein expression of peroxisome proliferator-activated receptor alpha (PPARα) and enhanced the protein expressions of carnitine palmitoyl transferase 1 and acyl-CoA oxidase 1. HMC inhibits lipid accumulation and promotes fatty acid oxidation by AMPK and PPARα pathways in free fatty acid-treated HepG2 cells, thereby attenuating hepatic steatosis.

Effects of Perfluorinated Alkyl Substances (PFAS) on Amphibian Body and Liver Conditions: Is Lipid Metabolism Being Perturbed throughout Metamorphosis?

Per- and polyfluoroalkyl substances (PFAS) may interact with peroxisome proliferator activated receptors (PPARs) and alter lipid homeostasis. Using Xenopus laevis, we investigated the effect of PFAS on (a) lipid homeostasis and whether this correlated to changes in body and hepatic condition; (b) the expression of hepatic genes regulated by PPAR; and (c) the hepatic lipidome. We chronically exposed tadpoles to 0.5 µg/L of either PFOS, PFHxS, PFOA, PFHxA, a binary mixture of PFOS and PFHxS (0.5 µg/L of each), or a control, from NF stage 52 through metamorphic climax. Growth, development, and survival were not affected, but we detected a sex-specific decrease in body condition at NF 66 (6.8%) and in hepatic condition (16.6%) across metamorphic climax for male tadpoles exposed to PFOS. We observed weak evidence for the transient downregulation of apolipoprotein-V (apoa5) at NF 62 in tadpoles exposed to PFHxA. Acyl-CoA oxidase 1 (acox1) was downregulated only in males exposed to PFHxS (Ln(Fold Change) = -0.54). We detected PFAS-specific downregulation of structural glycerophospholipids, while semi-quantitative profiling detected the upregulation in numerous glycerophospholipids, sphingomyelins, and diglycerides. Overall, our findings indicate that PFAS can induce sex-specific effects that change across larval development and metamorphosis. We demonstrate that PFAS alter lipid metabolism at environmentally relevant concentrations through divergent mechanisms that may not be related to PPARs, with an absence of effects on body condition, demonstrating the need for more molecular studies to elucidate mechanisms of PFAS-induced lipid dysregulation in amphibians and in other taxa.

Positive effects of a mixture of fish oil and soybean oil as a dietary lipid source on the ovarian development and health of female giant river prawn, Macrobrachium rosenbergii broodstock

Lipids are key nutrients that affect the development of the ovary in aquatic animals. This study aimed to investigate the effects of different lipid sources on the ovarian development and health of Macrobrachium rosenbergii broodstock. The M. rosenbergii broodstock, with an initial body weight of 8.07±0.74 g, were fed diets containing 5 % fish oil (FO), soya bean oil (SO), rapeseed oil (RO), coconut oil (CO), and a 1:1 mixture of fish oil and soybean oil (MO) as lipid sources for a period of 56 days. The results indicated that there were no significant differences in survival rate (SR) and hepatopancreatic index (HSI) among the different groups (P > 0.05). However, the specific growth rate (SGR) and gonadosomatic index (GSI) in the MO group were significantly higher than other groups (P < 0.05). Additionally, fatty acid levels in diets directly influenced the fatty acid composition of prawn hepatopancreas, showing a similar trend to that observed in the diet itself. Furthermore, compared to the other trial groups, haemolymph levels of 17-β estradiol (E2) and progesterone (PROG) were significantly increased in the MO group (P < 0.05). The ovarian section also exhibited better histomorphology and larger oocyte diameter in this group. Moreover, total antioxidant capacity was significantly increased in the MO group (P < 0.05). Saturated fatty acids in RO and CO groups could promote the expression of lipid synthesis-related genes fatty acid synthase (fas) and acetyl-CoA carboxylase (acc), concurrently suppressing the expression of lipid catabolism-related genes acyl-CoA oxidase-1 (acox-1) and AMP-activated protein kinase alpha (ampkα) (P < 0.05). Conversely, polyunsaturated fatty acids in the MO group significantly up-regulated the expression levels of fatty acid binding protein-3 (fabp-3) and peroxisome proliferator-activated receptor gamma (pparγ) (P < 0.05). Based on the findings of hepatopancreatic tissue structure, it was determined that the use of a single vegetable oil resulted in some damage to the hepatopancreatic tissue structure of M. rosenbergii broodstock, leading to increased oxidative stress. In conclusion, it is recommended that a 1:1 mixture of fish oil and soybean oil be used as a dietary lipid source to effectively meet the nutritional requirements during the ovarian development period of M. rosenbergii broodstock. This combination also enhances antioxidant properties, promotes the synthesis of haemolymph steroid hormones and lipid metabolism in female prawns, thereby facilitating ovarian development and overall health of M. rosenbergii broodstock.

Whole-genome resequencing reveals genetic diversity and selection signatures in five populations of Mandarin Fish (Siniperca chuatsi)

Mandarin fish is an important freshwater economic fish in China, and the genome of mandarin fish population may have specific selection signatures after long-term selection, and studying these selection signatures is one of the important strategies for screening functional genes. In this study, the whole genome was resequenced from five mandarin fish populations (HLJ, HN, AH, FJ, and BJ), and a total of high-quality SNPs with 1659,318 single nucleotide polymorphisms were obtained, and the genetic differentiation index and nucleotide polymorphism ratio between populations were used to detect the selected genomic regions. The results showed that all individuals were divided into two branches, with the HLJ population forming an independent cluster, and the HN, AH, FJ, and BJ populations clustering together. Selection signal analysis on the HLJ mandarin fish population and other mandarin fish populations using the FST and π HLJ/other methods. Finally, we identified 26 important candidate genes based on the enrichment pathways related to fat traits such as Glycerolipid metabolism, acyl-CoA oxidase activity, Wnt signaling pathway, and Notch signaling pathway, including notch3, pla2g12a and acox1. This study explores the genetic diversity and genetic structure of mandarin fish from a whole-genome perspective, identifies candidate genes related to fat traits, and provides references for the protection and utilization of mandarin fish genetic resources.

Variable Clinical Spectrum of Inborn Errors of Bile Acid Synthesis: A Report of 10 Cases.

Inborn errors of bile acid synthesis are rare genetic disorders that usually present as neonatal cholestasis and liver disease in older children and adults. The symptomatology of inborn errors of bile acid synthesis can markedly vary among individuals, ranging from mild to severe conditions. Diagnosis is based on genetic tests and/or urine liquid secondary ionization mass spectrometry. Here, we have described characteristics of patients who were diagnosed with inborn errors of bile acid synthesis in our department. We retrospectively evaluated data from patients diagnosed with inborn errors of bile acid synthesis by urine bile acid analysis and/or genetic tests between 2013 and 2023. Ten patients (8 boys, 2 girls) born to consanguineous parents were diagnosed with inborn errors of bile acid synthesis during the study period. Six patients were diagnosed with 3β-hydroxy-Δ5-C27-steroid dehydrogenase deficiency, 2 patients with peroxisomal acyl-CoA oxidase 2 deficiency, and 2 patients with peroxisome biogenesis disorder. In patients with 3β-hydroxy-Δ5-C27-steroid dehydrogenase deficiency, 3 patients were monitored with cholic acid treatment, 2 underwent liver transplant due to liver failure, and 1 patient died from liver failure. Ursodeoxycholic acid treatment was given to patients with acyl-CoA oxidase 2 deficiency. Cholic acid was given to patients with peroxisome biogenesis disorder. Inborn errors of bile acid synthesis can cause a variety of liver diseases, from asymptomatic liver enzyme elevation to cirrhosis. Clinical findings may include neurological symptoms and fat and fat-soluble vitamin malabsorption complications. Deficiency of 3β-hydroxy-Δ5-C27-steroid dehydrogenase is the most common bile acid synthetic defect presenting in cholestasis in infancy and childhood. Cholic acid is effective for most patients with inborn errors of bile acid synthesis. If patients do not receive an early diagnosis, progressive liver disease or other serious complications may develop.

Findings from the individualized management of a patient with Acyl-CoA Oxidase-1 (ACOX1) deficiency: A bedside-to-bench-to-bedside strategy

Acyl-CoA Oxidase-1 (ACOX1) deficiency (MIM 264470) is an autosomal recessive disease characterized by impairments in the desaturation of acyl-CoAs to 2-trans-enoyl-CoAs, which is the first step in the catalysis of the β-oxidative breakdown of very long chain fatty acids (VLCFA) occuring in peroxisomes. The deleterious accumulation of VLCFA in several organs, including the brain, is a key biochemical feature of this disease which has devastating neurological consequences. ACOX1 deficiency is ultra-rare; as such, few studies have been conducted to determine the leading causes of symptoms or uncover new therapeutics. When confronted with one such case, we decided to bring drug discovery tools to the patient's bedside in an attempt to identify a cure. A skin biopsy was performed on a young patient with ACOX1 deficiency, following which screening technologies and mass spectrometry analysis techniques were applied to design a cellular assay that enabled the direct measurement of the effect of small molecules on the patient's primary fibroblasts. This approach is particularly well adapted to inherited metabolic disorders such as ACOX1 deficiency. Through the evaluation of a proprietary library of repurposable drugs, we found that the anthelmintic drug niclosamide led to a significant reduction in VLCFA in vitro. This drug was subsequently administered to the patient for more than six years. This study outlines the screening and drug selection processes. Additionally, we present our comprehensive clinical and biochemical findings that aided in understanding the patient's natural history and analysis of the progression of the patient's symptoms throughout the treatment period. Although the patient's overall lifespan was extended compared to the average age at death in severe early onset cases of ACOX1 deficiency, we did not observe any definitive evidence of clinical or biochemical improvement during niclosamide treatment. Nonetheless, our study shows a good safety profile of long-term niclosamide administration in a child with a rare neurodegenerative disease, and illustrates the potential of individualized therapeutic strategies in the management of inherited metabolic disorders, which could benefit both patients and the broader scientific and medical communities.

Dynamic Change of Volatile Fatty Acid Derivatives (VFADs) and Their Related Genes Analysis during Innovative Black Tea Processing

Volatile fatty acid derivatives (VFADs) play a significant role in contributing to flowery–fruity flavor black tea. Innovative black tea is typically crafted from aroma-intensive tea cultivars, such as Jinmudan, using defined production methodologies. In this study, the during-processing tea leaves of innovative black tea were applied as materials, and we selected a total of 45 VFADs, comprising 11 derived aldehydes, nine derived alcohols, and 25 derived esters. Furthermore, the dynamic variations of these VFADs were uncovered. Transcriptome analysis was performed to identify genes involved in the LOX (lipoxygenase) pathway, resulting in the identification of 17 CsLOX genes, one hydrogen peroxide lyase (CsHPL) gene, 11 alcohol dehydrogenases (CsADH) genes, 11 genes as acyl CoA oxidase (CsACOX) genes, and three allene oxide synthase (CsAOS) genes. Additionally, the expression levels of these genes were measured, indicating that the processing treatments of innovative black tea, particularly turn-over and fermentation, had a stimulation effect on most genes. Finally, qRT-PCR verification and correlation analysis were conducted to explain the relationship between VFADs and candidate genes. This study aims to provide a reference for illuminating the formation mechanisms of aroma compounds in innovative black tea, thereby inspiring the optimization of innovative processing techniques and enhancing the overall quality of black tea.

Tumor-derived exosomal miR-103a-3p promotes vascular permeability and proliferation by targeting ZO-1 and ACOX-1 in nasopharyngeal carcinoma.

miR-103a-3p has been reported to be a factor leading to poor prognosis in several human malignancies, including nasopharyngeal carcinoma (NPC). Secreted microRNAs containing exosomes may mediate the communication between cancer and stromal cells. The purpose of the current work was to learn more about miR-103a-3p's function in NPC exosomes. Transmission electron microscopy and NanoSight analysis were used to verify the existence of exosomes. To determine the relationship between exosomal miR-103a-3p and carcinogenesis in NPC, gain- and loss-of-function studies were carried out. Cell Counting Kit-8 (CCK8), 5-ethynyl-2'-deoxyuridine (EdU) cell proliferation assay, colony formation, flow cytometry, trans-endothelial invasion assays, endothelial permeability and cellular immunofluorescence were used to identify roles of exosomal miR-103a-3p in vitro. Zebrafish assay was used to disclose the effect of exosomal miR-103a-3p in vivo. Bioinformatics and dual-luciferase reporter assay were applied to clarify the mechanism of exosomal miR-103a-3p regulating the crosstalk between NPC cells and human umbilical vein endothelial cells (HUVECs). In the present study, we first demonstrated that the overexpression of exosomal miR-103a-3p improved NPC cell proliferation, migration, and the epithelial-mesenchymal transition (EMT) progression in vitro. Then, we verified that NPC cell-derived exosomal miR-103a-3p destroyed the integrity of the endothelial monolayer in vitro and in vivo by downregulating zonula occludens 1 (ZO-1) expression. Moreover, we revealed that miR-103a-3p containing exosomes facilitated NPC cell proliferation through lipid droplet accumulation by direct target to metabolic enzyme acyl-CoA oxidase 1 (ACOX-1). Our data demonstrate that exosomal miR-103a-3p can facilitate the development of NPC by regulating the crosstalk between NPC cells and HUVECs. Exosomal miR-103a-3p could potentially serve as a therapeutic target for NPC.

Activation of LONP1 by 84-B10 alleviates aristolochic acid nephropathy via re-establishing mitochondrial and peroxisomal homeostasis

Pharmaceutical formulations derived from Aristolochiaceae herbs, which contain aristolochic acids (AAs), are widely used for medicinal purposes. However, exposure to these plants and isolated AAs is linked to renal toxicity, known as AA nephropathy (AAN). Currently, the mechanisms underlying AAN are not fully understood, leading to unsatisfactory treatment strategies. In this study, we explored the protective role of 84-B10 (5-[[2-(4-methoxyphenoxy)-5-(trifluoromethyl) phenyl] amino]-5-oxo-3-phenylpentanoic acid) against AAN. RNA-seq analysis revealed that the mitochondrion and peroxisome were the most affected cellular components following 84-B10 treatment in AAN mice. Consistently, 84-B10 treatment preserved mitochondrial ultrastructure, restored mitochondrial respiration, enhanced the expression of key transporters (carnitine palmitoyltransferase 2) and enzymes (acyl-Coenzyme A dehydrogenase, medium chain) involved in mitochondrial fatty acid β-oxidation, and reduced mitochondrial ROS generation in both aristolochic acid I (AAI)-challenged mice kidneys and cultured proximal tubular epithelial cells. Additionally, 84-B10 treatment increased the expression of key transporters (ATP binding cassette subfamily D) and rate-limiting enzymes (acyl-CoA oxidase 1) involved in peroxisomal fatty acid β-oxidation and restored peroxisomal redox balance. Knocking down LONP1 expression diminished the protective effects of 84-B10 against AAN, suggesting LONP1-dependent protection. In conclusion, our study provides evidence that AAN is associated with significant disturbances in both mitochondrial and peroxisomal functions. The LONP1 activator 84-B10 demonstrates therapeutic potential against AAN, likely by maintaining homeostasis in both mitochondria and peroxisomes.

Inhibitory activity and antioomycete mechanism of citral against Phytophthora capsici

The natural terpenoid citral has antifungal activity against multiple fungi, but its bioactivity against oomycetes is unclear. Therefore, this study investigated the antioomycete activity and mechanism of citral against Phytophthora capsici, a highly destructive invasive oomycete. Results showed that citral not only had a great inhibition on the mycelial growth of P. capsici (EC50 = 94.15 mg/L), but also had a significant inhibition on multiple spores, such as sporangia formation, zoospore discharge and zoospore germination. Citral at 4000 mg/L exhibited favorable protective (73.33%) and curative efficacy (55.11%) against pepper Phytophthora blight. Citral significantly damaged the hyphal morphology, disrupted the cell membrane integrity, increased the permeability of cell membrane, and increased the glycerol content in P. capsici. A total of 250 upregulated and 288 downregulated proteins were identified in iTRAQ-based quantitative proteomic analysis. Downregulated proteins were mostly enriched in pathways of ABC transporters, cyanoamino acid metabolism and starch and sucrose metabolism, suggesting an inhibition of citral on transmembrane transporter (e.g., ABC transporters) and pathogenicity (e.g., β-glucosidases) proteins. Upregulated proteins were enriched in biosynthesis of unsaturated fatty acids, pyruvate metabolism and glycolysis/gluconeogenesis, suggesting an activation of citral on energy generation proteins, including acyl-CoA oxidase, D-lactate dehydrogenase, pyruvate kinase, acetyl-CoA synthetase and phosphoenolpyruvate carboxykinase. Biochemical and iTRAQ analysis suggested that cell membrane may be the target of citral in P. capsici.

SH-SY5Y cells undergo changes in peroxisomal metabolism when exposed to decanoic acid.

Medium-chain fatty acids (MCFAs), particularly decanoic acid (C10) and octanoic acid (C8), have garnered attention in recent years for their potential antiepileptic properties. A previous study from our laboratory demonstrated that C10 targets the PPARγ nuclear receptor, increasing the activity of the antioxidant enzyme catalase and thereby possibly modulating peroxisomal content. Here, we examined markers of peroxisomal content and activity in response to C10 and C8 exposure in neuronal-like SH-SY5Y cells. SH-SY5Y were treated with 250 mM C10 or C8 for a period of 6 days. Following this, biochemical markers of peroxisomal content and function were assessed, including acyl-coA oxidase activity, peroxisomal gene expression and peroxisomal VLCFA β-oxidation. Our findings revealed that C10 treatment augments acyl-CoA oxidase 1 (ACOx1) activity by 129% in comparison to control cells. An exploration into genes related to peroxisomal biosynthesis showed 23% increased expression of PEX11α upon C10 exposure, implying peroxisomal proliferation. Furthermore, it was observed that C10 exposure not only elevated ACOx1 activity but also enhanced peroxisomal β-oxidation of docosanoic acid (C22). Our findings bolster the premise that C10 functions as a peroxisome proliferator, influencing peroxisomal content and function. Further investigations are required to fully understand the mechanistic details as to how this may be beneficial in epilepsy and the potential implications with regards to peroxisomal disease.

HAO2 protects from proximal tubular cells injured in rats with chronic kidney disease by promoting fatty acid metabolic processes

The complex pathogenesis of kidney disease is closely related to the diversity of kidney intrinsic cells. In this study, single-cell transcriptome sequencing technology was used to sequence and analyze blood and kidney tissue cells in normal control rats and rats with chronic kidney disease (CKD), focusing on key cell populations and functional enrichment to explore the pathogenesis of CKD. Oil red O staining and enzyme-linked immunosorbent assay (ELISA) were used to detect lipid droplets and free fatty acid (FFA). Quantitative real-time polymerase chain reaction (RT-PCR), western blot (WB) were used to verify the differential gene hydroxyacid oxidase 2 (HAO2) and fatty acid metabolic process in tissue to ensure the reliability of single-cell sequencing results. We successfully established a single-cell transcriptome atlas of blood and kidney tissue in rats with CKD, which were annotated into 14 cell subsets (MPCs, PT, Tc, DCT, B-IC, A-IC, CNT, ALOH, BC, Neu, Endo, Pla, NKT, Baso) according to marker gene, and the integrated single-cell atlas of rats showed a significant increase and decrease of MPCs and PTs in the CKD group, respectively. Functional analysis found extensive enrichment of metabolic-related pathways in PT cells, includes fatty acid metabolic process, cellular amino acid metabolic process and generation of precursor metabolites and energy. Immunohistochemical experiments determined that the differential gene HAO2 was localized in the renal tubules, and its expression was significantly reduced in CKD group compared with control, and oil red O staining showed that lipid droplets increased in the CKD group, after overexpression of HAO2 the lipid droplets was inhibited. ELISA assay showed that ATP content decreased in the CKD group and FFA increased in the CKD group. Moreover, the mitochondrial membrane potential of the cells in the OE-HAO2 group was significantly increased compared with OE-NC. The acyl-CoA oxidase 1(ACOX1), peroxisome proliferator-activated receptor alpha (PPARα), peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α) were decreased in the CKD group, while genes and proteins were increased after overexpression of HAO2, and the AMP-activated protein kinase (AMPK) phosphorylated proteins were increased, the acetyl-CoA carboxylase (ACC) phosphorylated proteins were decreased, reversely. Therefore, HAO2 may be an important regulator of fatty acid metabolic processes in CKD, and overexpression of HAO2 can enhance fatty acid metabolism by promoting fatty acid oxidation (FAO) pathway.

Dermatopathological features and successful treatment with topical antioxidant for ichthyosiform lesions in Mitchell syndrome caused by an ACOX1 variant

AbstractPeroxisomal acyl‐CoA oxidase 1 (ACOX1), is a peroxisomal enzyme that catalyzes β‐oxidation of very‐long‐chain fatty acids (VLCFA). The gain‐of‐function variant p.Asn237Ser in ACOX1 has been shown to cause Mitchell syndrome (MITCH), a neurodegenerative disorder characterized by episodic demyelination, hearing loss, and polyneuropathy, through the overproduction of hydrogen peroxide. Only eight cases of MITCH have been reported. While all these patients experienced cutaneous abnormalities, detailed skin features and potential treatment have not been documented. Herein, we report two MITCH patients who harbored a de novo heterozygous variant p.Asn237Ser in ACOX1 and experienced progressive ichthyosiform erythroderma. Skin histopathology revealed hyperkeratosis and parakeratosis with focal hypogranulosis as well as dyskeratotic keratinocytes. Lipid accumulation in the epidermis was observed using Oil Red O staining. Both patients exhibited a remarkable response to treatment with the topical antioxidant N‐acetylcysteine (NAC), with Patient 1 achieving complete recovery after 3 months of consistent treatment. This study provides the first comprehensive description of the clinicopathological characteristics and effective treatment of skin lesions in MITCH patients. The successful treatment with topical NAC suggests excessive reactive oxygen species might play a significant role in the pathogenesis of skin lesions in MITCH.

ELOVL5 and VLDLR synergistically affect n-3 PUFA deposition in eggs of different chicken breeds

There was no significant difference in the composition and content of fatty acids in eggs among different breeds initially, but following the supplementation of flaxseed oil, Dwarf Layer were observed to deposit more n-3 polyunsaturated fatty acid (PUFA) in eggs. Currently, there is limited research on the mechanisms underlying the differences in egg composition among different breeds. Therefore, in this study, 150 twenty-four-wk-old hens of each breed, including the Dwarf Layer and White Leghorn, were fed either a basal diet or a diet supplemented with 2.5% flaxseed oil. After 28 d, eggs and liver samples were collected to determine fatty acid composition, and serum, liver, intestine, and follicles were collected for subsequent biochemical, intestinal morphology, and lipid metabolism-related genes expression analysis. Duodenal contents were collected for microbial analysis. The results showed that there was no significant difference in the content and deposition efficiency of total n-3 PUFA in the liver of the 2 breeds, but the content and deposition efficiency of total n-3 PUFA in the egg of Dwarf Layer were significantly higher than those of White Leghorn after feeding flaxseed oil. Flaxseed oil and breeds did not have significant effects on cholesterol (CHO), free fatty acids (NEFA), low-density lipoprotein (LDL), and estrogen (E2) levels. After feeding with flaxseed oil, the villus height and the villus-to-crypt ratio in both breeds were increased and duodenal crypt depth was decreased. The villus-to-crypt ratio (4.78 vs. 3.60) in the duodenum of Dwarf Layer was significantly higher than that in White Leghorn after feeding with flaxseed oil. Flaxseed oil can impact the gut microbiota in the duodenum and reduce the microbiota associated with fatty acid breakdown, such as Romboutsia, Subdolibranulum, Lachnochlostridium, and Clostridium. This may mean that less ALA can be decomposed and more ALA can be absorbed into the body. Additionally, after feeding flaxseed oil, the mRNA levels of elongation enzymes 5 (ELOVL5), fatty acid desaturase 1 (FADS1), and fatty acid transporter 1 (FATP1) in the liver of Dwarf Layer were significantly higher than those in White Leghorn, while the mRNA levels of peroxisome proliferator-activated receptor alpha (PPAR), carnitine palmitoyl transferase 1 (CPT1), Acyl CoA oxidase 1 (ACOX1), and Acyl-CoA synthetase (ACSL) were significantly lower than those in White Leghorn. The mRNA level of FABP1 in the duodenum of Dwarf Layer was significantly higher than that of White Leghorn, while the mRNA level of FATP1 was significantly lower than that of White Leghorn. The protein levels of ELOVL5 in the liver of Dwarf Layer and very low-density lipoprotein receptor (VLDLR) in the follicles were significantly higher than those of White Leghorn. In summary, after feeding flaxseed oil, the higher ratio of villus height to crypt depth in Dwarf Layer allows more α-linolenic acid (ALA) to be absorbed into the body. The higher mRNA expression of FADS1, ELOVL5, and FATP1, as well as the higher protein expression of ELOVL5 in the liver of Dwarf Layer enhance the conversion of ALA into DHA. The higher protein expression of VLDLR in follicles of Dwarf Layer allows more n-3 PUFA to deposit in the follicles. These combined factors contribute to the Dwarf Layer's ability to deposit higher levels of n-3 PUFA in eggs, as well as improving the deposition efficiency of n-3 PUFA.

Asprosin aggravates nonalcoholic fatty liver disease via inflammation and lipid metabolic disturbance mediated by reactive oxygen species.

Asprosin (ASP) is a newly-identified adipokine and plays important roles in energy metabolism homeostasis. However, there is no report on whether and how ASP is involved in the pathogenesis of nonalcoholic fatty liver disease (NAFLD). Therefore, in the study, we investigated the protective effects of ASP-deficiency on the liver in the NAFLD model mice and the detrimental effects of ASP treatment on the human normal hepatocytes (LO2 cell line). More important, we explored the underlying mechanism from the perspective of lipid metabolism and inflammation. In the in vivo experiments, our data showed that the ASP-deficiency significantly alleviated the high-fat diet-induced inflammation and NAFLD, inhibited the hepatic fat deposition and downregulated the expressions of fat acid synthase (FASN), peroxisome proliferator-activated receptor γ (PPARγ) and forkhead box protein O1 (FOXO1); moreover, the ASP-deficiency attenuated the inflammatory state and inhibited the activation of the IKK/NF-κBp65 inflammation pathway. In the in vitro experiments, our results revealed that ASP treatment caused and even exacerbated the injury of LO2 cells induced by FFA; In contrast, the ASP treatment upregulated the expressions of PPARγ, FOXO1, FASN, ACC and acyl-CoA oxidase 1 (ACOX1) and elevated the reactive oxygen species (ROS) levels. Accordingly, these results demonstrate that ASP causes NAFLD through disrupting lipid metabolism and promoting the inflammation mediated by ROS.

Dietary dicarboxylic acids provide a non-storable alternative fat source that protects mice against obesity.

Dicarboxylic fatty acids are generated in the liver and kidney in a minor pathway called fatty acid ω-oxidation. The effects of consuming dicarboxylic fatty acids as an alternative source of dietary fat have not been explored. Here, we fed dodecanedioic acid, a 12-carbon dicarboxylic (DC12), to mice at 20% of daily caloric intake for nine weeks. DC12 increased metabolic rate, reduced body fat, reduced liver fat, and improved glucose tolerance. We observed DC12-specific breakdown products in liver, kidney, muscle, heart, and brain, indicating that oral DC12 escaped first-pass liver metabolism and was utilized by many tissues. In tissues expressing the "a" isoform of acyl-CoA oxidase-1 (ACOX1), a key peroxisomal fatty acid oxidation enzyme, DC12 was chain shortened to the TCA cycle intermediate succinyl-CoA. In tissues with low peroxisomal fatty acid oxidation capacity, DC12 was oxidized by mitochondria. In vitro, DC12 was catabolized even by adipose tissue and was not stored intracellularly. We conclude that DC12 and other dicarboxylic acids may be useful for combatting obesity and for treating metabolic disorders.

Elucidation of novel drought-responsive genes from tuber transcriptome of cassava under water deficit stress

Cassava (Manihot esculenta Carntz) is the major starchy root crop grown in the tropical parts of the world. Two cassava clones contrasting for their drought tolerance capacity (8S501- drought tolerant and H97-drought sensitive) were selected and grown in the field for studying the agronomical and molecular changes in both the clones under drought stress conditions. A reduction in the number of tuberous roots per plant, tuberous root length, average single tuber weight and tuber yield per plant was observed under drought stress when compared with the control conditions and also significantly lower mean values were observed for the sensitive clone H97 than that of the tolerant clone 8S501 when measured at 60 days of stress. Transcriptome sequencing of the tuber tissues of the two clones was done at 60 days of imposing drought stress. Different genes belonging to various groups like aquaporins, transporter genes, growth regulator related genes, calcium binding and mineral transfer-related genes, transferase genes and transcription factors were differentially expressed in the tubers under drought stress. Comparative transcriptomics revealed that acyl-CoA oxidase, primary-amine oxidase, glutathione peroxidase, vesicle transport, late embryogenesis abundant protein related, histone demethylase, BR-signaling kinase, palmitoyltransferase, DNA mismatch repair protein, heat shock protein related, starch/sucrose metabolic pathway related and MFS transporter genes were differentially expressed in the tubers of the tolerant clone 8S501 relative to the susceptible clone H97.

Essential phospholipids impact cytokine secretion and alter lipid-metabolizing enzymes in human hepatocyte cell lines

BackgroundEssential phospholipids (EPL) are hepatoprotective.MethodsThe effects on interleukin (IL)-6 and -8 secretion and on certain lipid-metabolizing enzymes of non-cytotoxic concentrations of EPL (0.1 and 0.25 mg/ml), polyenylphosphatidylcholine (PPC), and phosphatidylinositol (PtdIns) (both at 0.1 and 1 mg/ml), compared with untreated controls, were assessed in human hepatocyte cell lines (HepG2, HepaRG, and steatotic HepaRG).ResultsLipopolysaccharide (LPS)-induced IL-6 secretion was significantly decreased in HepaRG cells by most phospholipids, and significantly increased in steatotic HepaRG cells with at least one concentration of EPL and PtdIns. LPS-induced IL-8 secretion was significantly increased in HepaRG and steatotic HepaRG cells with all phospholipids. All phospholipids significantly decreased amounts of fatty acid synthase in steatotic HepaRG cells and the amounts of acyl-CoA oxidase in HepaRG cells. Amounts of lecithin cholesterol acyltransferase were significantly decreased in HepG2 and HepaRG cells by most phospholipids, and significantly increased with 0.1 mg/ml PPC (HepaRG cells) and 1 mg/ml PtdIns (steatotic HepaRG cells). Glucose-6-phosphate dehydrogenase activity was unaffected by any phospholipid in any cell line.ConclusionsEPL, PPC, and PtdIns impacted the secretion of pro-inflammatory cytokines and affected amounts of several key lipid-metabolizing enzymes in human hepatocyte cell lines. Such changes may help liver function improvement, and provide further insights into the EPL’s mechanism of action.

Effect of Mechanical Damage in Green-Making Process on Aroma of Rougui Tea.

Rougui Tea (RGT) is a typical Wuyi Rock Tea (WRT) that is favored by consumers for its rich taste and varied aroma. The aroma of RGT is greatly affected by the process of green-making, but its mechanism is not clear. Therefore, in this study, fresh leaves of RGT in spring were picked, and green-making (including shaking and spreading) and spreading (unshaken) were, respectively, applied after sun withering. Then, they were analyzed by GC-TOF-MS, which showed that the abundance of volatile compounds with flowery and fruity aromas, such as nerolidol, jasmine lactone, jasmone, indole, hexyl hexanoate, (E)-3-hexenyl butyrate and 1-hexyl acetate, in green-making leaves, was significantly higher than that in spreading leaves. Transcriptomic and proteomic studies showed that long-term mechanical injury and dehydration could activate the upregulated expression of genes related to the formation pathways of the aroma, but the regulation of protein expression was not completely consistent. Mechanical injury in the process of green-making was more conducive to the positive regulation of the allene oxide synthase (AOS) branch of the α-linolenic acid metabolism pathway, followed by the mevalonate (MVA) pathway of terpenoid backbone biosynthesis, thus promoting the synthesis of jasmonic acid derivatives and sesquiterpene products. Protein interaction analysis revealed that the key proteins of the synthesis pathway of jasmonic acid derivatives were acyl-CoA oxidase (ACX), enoyl-CoA hydratase (MFP2), OPC-8:0 CoA ligase 1 (OPCL1) and so on. This study provides a theoretical basis for the further explanation of the formation mechanism of the aroma substances in WRT during the manufacturing process.