Edited by Dennis R. VoelkerA chronic high fat diet results in hepatic mitochondrial dysfunction and induction of peroxisomal fatty acid oxidation (FAO); whether specific inhibition of peroxisomal FAO benefits mitochondrial FAO and reactive oxygen species (ROS) metabolism remains unclear. In this study a specific inhibitor for the rate-limiting enzyme involved in peroxisomal FAO, acyl-CoA oxidase-1 (ACOX1) was developed and used for the investigation of peroxisomal FAO inhibition upon mitochondrial FAO and ROS metabolism. Specific inhibition of ACOX1 by 10,12-tricosadiynoic acid increased hepatic mitochondrial FAO via activation of the SIRT1-AMPK (adenosine 5-monophosphateactivated protein kinase) pathway and proliferator activator receptor ␣ and reduced hydrogen peroxide accumulation in high fat diet-fed rats, which significantly decreased hepatic lipid and ROS contents, reduced body weight gain, and decreased serum triglyceride and insulin levels. Inhibition of ACOX1 is a novel and effective approach for the treatment of high fat dietor obesity-induced metabolic diseases by improving mitochondrial lipid and ROS metabolism.
Hepatic lipid and reactive oxygen species (ROS)2 accumulation due to hyperlipidemia and obesity are critical factors associated with the prevalence of metabolic and cardiovascular diseases (1, 2). Decreased mitochondrial fatty acid oxidation (FAO) and increased lipogenesis are major contributors to lipid accumulation in liver and other tissues (3). Excessive hepatic ROS generation and decreased cellular antioxidative activity lead to oxidative stress and hepatic oxidative injury (2, 4). Agents that are able to promote mitochondrial fatty acid oxidation or have antilipogenic and antioxidative effects will improve lipid and ROS metabolism and attenuate hepatic steatosis and oxidative injury.Peroxisomes are subcellular respiratory organelles that are critical for the metabolism of long chain and branched-chain fatty acids (5). Peroxisomes are sensitive to external signals and are easy to proliferate under conditions of high fat diet (HFD) (6, 7), diabetes (8), or hypolipidemic drug treatment (9); peroxisomal FAO is induced, oxidation capacity is increased by 2-10-fold, and peroxisomal FAO is regulated by the peroxisome proliferator activator receptor ␣ isoform (PPAR␣) (5).Acyl-CoA oxidase-1 (ACOX1, EC 1.3.3.6) is a flavoenzyme that catalyzes the initial and rate-determining reaction of the classical peroxisomal FAO using straight-chain fatty acyl-CoAs as the substrates, which donates electrons to molecular oxygen generating hydrogen peroxide; this byproduct is further decomposed by catalase, as shown in Fig. 1. The classical peroxisomal FAO has been known for nearly 40 years (9), but it is still not clear about the exact role of peroxisomal FAO in cellular fatty acid metabolism and especially its effect on mitochondrial fatty acid oxidation. Several lines of evidence have shown that chronic induction of peroxisomal FAO may cause oxidative stress and is potentially detrimental to mitochondrial fa...
Although it is known that inflammation is involved in Parkinson’s disease (PD) pathogenesis and vitamin K2 (VK2) has anti-inflammatory effects, to date few studies have been reported on the relationship between VK2 and PD development. Herein we presented a case-control study involving 93 PD patients and 95 healthy controls. Overall, the serum VK2 level of PD patients (3.49 ± 1.68 ng/ml) was significantly lower than that of healthy controls (5.77 ± 2.71 ng/ml). When the PD patients were stratified by disease progression, we observed that the serum VK2 level of late stage patients was further decreased to 3.15 ± 1.18 ng/ml while the serum VK2 level of early stage patients was 3.92 ± 2.09 ng/ml. Furthermore, the curve analysis showed that the serum VK2 level decreased gradually with the increment of PD Hoehn-Yahr (H-Y) stage. We also confirmed the dysregulated inflammatory responses and coagulation cascades in PD patients by public dataset, which are associated to the decreased VK2 level. In summary, we found the serum VK2 level in PD patients is lower than that in healthy controls. The decrease of VK2 level may be related to the occurrence and progression of PD by loosening the regulation of inflammatory responses and coagulation cascades signal.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.