ACOX1
Peroxisomal acyl-coenzyme A oxidase 1 (EC 1.3.3.6) (AOX) (Palmitoyl-CoA oxidase) (Straight-chain acyl-CoA oxidase) (SCOX) [Contains: Peroxisomal acyl-CoA oxidase 1, A chain; Peroxisomal acyl-CoA oxidase 1, B chain; Peroxisomal acyl-CoA oxidase 1, C chain] [ACOX]
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Methionine (Met) is one of the most important amino acids in fish feed. The effects of dietary Met on lipid deposition in fish varied a lot among different studies. The present study was aimed at investigating the effects of dietary Met supplementation on the lipid accumulation in tiger puffer, which have a unique lipid storage pattern. Crystalline L-Met was supplemented to a low-fishmeal control diet to obtain two experimental diets with a low (1.1% of dry weight, L-MET) or high Met level (1.6% of dry weight, H-MET). A 67-day feeding trial was conducted with juvenile tiger puffer (average initial weight, 13.83 g). Each diet was fed to triplicate tanks (30 fish in each tank). The results showed that the total lipid contents in whole-body and liver significantly increased with increasing dietary Met levels. The hepatosomatic index, weight gain, and total bile acid content in serum showed similar patterns in response to dietary Met treatments, while the lipid content in muscle was not affected. The hepatic contents of 18-carbon fatty acids were elevated by dietary Met supplementation. The Hepatic mRNA expression of lipogenetic gene such as FAS, GPAT, PPARγ, ACLY, and SCD1 was down-regulated, while the gene expression of lipolytic genes ACOX1 and HSL, as well as that of ApoB100, were up-regulated by increasing dietary Met levels. The hepatic lipidomics of experimental fish was also analyzed. In conclusion, increasing dietary Met levels (0.61%, 1.10%, and 1.60%) increased the hepatic lipid accumulation in tiger puffer. The mechanisms involved warrant further studies.
MeSH Terms
- Aging
- Animals
- Diet
- Dietary Supplements
- Fatty Acids
- Lipid Metabolism
- Liver
- Methionine
- Takifugu
Keywords
- Diet
- Lipid
- Methionine
- Takifugu rubripes
To clarify appropriateness of current claims for health and wellness virtues of argan oil, studies were conducted in inflammatory states. LPS induces inflammation with reduction of PGC1-[i]α[/i] signaling and energy metabolism. Argan oil protected the liver against LPS toxicity and interestingly enough preservation of peroxisomal acyl-CoA oxidase type 1 (ACOX1) activity against depression by LPS. This model of LPS-driven toxicity circumvented by argan oil along with a key anti-inflammatory role attributed to ACOX1 has been here transposed to model aging. This view is consistent with known physiological role of ACOX1 in yielding precursors of specialized proresolving mediators (SPM) and with characteristics of aging and related disorders including reduced PGC1-[i]α[/i] function and improvement by strategies rising ACOX1 (via hormonal gut FGF19 and nordihydroguaiaretic acid in metabolic syndrome and diabetes conditions) and SPM (neurodegenerative disorders, atherosclerosis, and stroke). Delay of aging to resolve inflammation results from altered production of SPM, SPM improving most aging disorders. The strategic metabolic place of ACOX1, upstream of SPM biosynthesis, along with ability of ACOX1 preservation/induction and SPM to improve aging-related disorders and known association of aging with drop in ACOX1 and SPM, all converge to conclude that ACOX1 represents a previously unsuspected and currently emerging antiaging protein.
MeSH Terms
- Acyl-CoA Oxidase
- Aging
- Animals
- Anti-Inflammatory Agents
- Disease Models, Animal
- Humans
- Lipopolysaccharides
- Oxidoreductases
- Plant Oils
Hepatic steatosis is frequently observed in obese and aged individuals. Because hepatic steatosis is closely associated with metabolic syndromes, including insulin resistance, dyslipidemia, and inflammation, numerous efforts have been made to develop compounds that ameliorate it. Here, a novel peroxisome proliferator-activated receptor (PPAR) α agonist, 4-(benzo[d]thiazol-2-yl)benzene-1,3-diol (MHY553) was developed, and investigated its beneficial effects on hepatic steatosis using young and old Sprague-Dawley rats and HepG2 cells.Docking simulation and Western blotting confirmed that the activity of PPARα, but not that of the other PPAR subtypes, was increased by MHY553 treatment. When administered orally, MHY553 markedly ameliorated aging-induced hepatic steatosis without changes in body weight and serum levels of liver injury markers. Consistent with in vivo results, MHY553 inhibited triglyceride accumulation induced by a liver X receptor agonist in HepG2 cells. Regarding underlying mechanisms, MHY553 stimulated PPARα translocation into the nucleus and increased mRNA levels of its downstream genes related to fatty acid oxidation, including CPT-1A and ACOX1, without apparent change in lipogenesis signaling. Furthermore, MHY553 significantly suppresses inflammatory mRNA expression in old rats. In conclusion, MHY553 is a novel PPARα agonist that improved aged-induced hepatic steatosis, in part by increasing β-oxidation signaling and decreasing inflammation in the liver. MHY553 is a potential pharmaceutical agent for treating hepatic steatosis in aging.
MeSH Terms
- Aging
- Animals
- Biomarkers
- Body Weight
- Cytokines
- Disease Models, Animal
- Fatty Acids
- Fatty Liver
- Gene Expression Regulation
- Hep G2 Cells
- Humans
- Inflammation
- Inflammation Mediators
- Lipid Metabolism
- Models, Molecular
- Molecular Conformation
- Oxidation-Reduction
- PPAR alpha
- Protein Transport
- Rats
- Transcription, Genetic
Keywords
- MHY553
- PPARα agonist
- aging
- fatty acid oxidation
- hepatic steatosis
The lack of high-throughput methods to analyze the adipose tissue protein composition limits our understanding of the protein networks responsible for age and diet related metabolic response. We have developed an approach using multiple-dimension liquid chromatography tandem mass spectrometry and extended multiplexing (24 biological samples) with tandem mass tags (TMT) labeling to analyze proteomes of epididymal adipose tissues isolated from mice fed either low or high fat diet for a short or a long-term, and from mice that aged on low [i]versus[/i] high fat diets. The peripheral metabolic health (as measured by body weight, adiposity, plasma fasting glucose, insulin, triglycerides, total cholesterol levels, and glucose and insulin tolerance tests) deteriorated with diet and advancing age, with long-term high fat diet exposure being the worst. In response to short-term high fat diet, 43 proteins representing lipid metabolism ([i]e.g.[/i] AACS, ACOX1, ACLY) and red-ox pathways ([i]e.g.[/i] CPD2, CYP2E, SOD3) were significantly altered (FDR < 10%). Long-term high fat diet significantly altered 55 proteins associated with immune response ([i]e.g.[/i] IGTB2, IFIT3, LGALS1) and rennin angiotensin system ([i]e.g.[/i] ENPEP, CMA1, CPA3, ANPEP). Age-related changes on low fat diet significantly altered only 18 proteins representing mainly urea cycle ([i]e.g.[/i] OTC, ARG1, CPS1), and amino acid biosynthesis ([i]e.g.[/i] GMT, AKR1C6). Surprisingly, high fat diet driven age-related changes culminated with alterations in 155 proteins involving primarily the urea cycle ([i]e.g.[/i] ARG1, CPS1), immune response/complement activation ([i]e.g.[/i] C3, C4b, C8, C9, CFB, CFH, FGA), extracellular remodeling ([i]e.g.[/i] EFEMP1, FBN1, FBN2, LTBP4, FERMT2, ECM1, EMILIN2, ITIH3) and apoptosis ([i]e.g.[/i] YAP1, HIP1, NDRG1, PRKCD, MUL1) pathways. Using our adipose tissue tailored approach we have identified both age-related and high fat diet specific proteomic signatures highlighting a pronounced involvement of arginine metabolism in response to advancing age, and branched chain amino acid metabolism in early response to high fat feeding. Data are available via ProteomeXchange with identifier PXD005953.
MeSH Terms
- Adipose Tissue
- Aging
- Animals
- Diet, High-Fat
- Epididymis
- Gene Regulatory Networks
- Immunoblotting
- Male
- Mass Spectrometry
- Metabolic Networks and Pathways
- Mice, Inbred C57BL
- Proteome
- Proteomics
- Reproducibility of Results
- Sample Size
Peroxisomal β-oxidation is primarily responsible for the degradation of very long chain fatty acids (VLCFAs), dicarboxylic acids, unsaturated fatty acids and branched fatty acids. The genes encoding β-oxidation enzymes are transcriptionally regulated by peroxisome proliferator-activated receptor alpha (PPARα). Age-related decreases in acyl-CoA oxidase 1 (ACOX1) activity, a key enzyme involved in peroxisomal β-oxidation, have been found in aged rodents. To determine whether decreased peroxisomal β-oxidation with aging affects brain fatty acid composition, 22-month-old (old) and 3-month-old (young) male Sprague-Dawley rats were used. We confirmed the decreased expression of liver ACOX1 and PPARα in old rats. In addition, a gas chromatography assay showed significant changes in the percentage of fatty acids in the cerebral cortices between old and young rats. In the cerebral cortices of old rats, the increased fatty acids included VLCFAs (C20:0, C22:0, C24:0) and monounsaturated fatty acids (C16:1, C18:1, C20:1, C22:1, C24:1), whereas the decreased fatty acids included C18:0, C20:4 and C22:6. These results indicated that decreased liver peroxisomal β-oxidation was accompanied by changes in brain fatty acid composition with aging and suggested that peroxisomal β-oxidation dysfunction may play a potential role in the progression of brain aging.
MeSH Terms
- Acyl-CoA Oxidase
- Aging
- Animals
- Blotting, Western
- Cerebral Cortex
- Chromatography, Gas
- Fatty Acids
- Fatty Acids, Monounsaturated
- Liver
- Male
- Oxidation-Reduction
- PPAR alpha
- RNA, Messenger
- Rats
- Rats, Sprague-Dawley
- Reverse Transcriptase Polymerase Chain Reaction