Amelioration of Lipid Abnormalities by α‐Lipoic acid Through Antioxidative and Anti‐Inflammatory Effects

Zhang, Yongyan; Han, Ping; Wu, Na; He, Bing; Lü, Yan; Li, Shuwen; Liu, Yang; Zhao, S. J.; Liu, Letong; Li, Yan

doi:10.1038/oby.2011.121

Cited by 113 publications

(84 citation statements)

References 40 publications

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“…Our results demonstrated that LA induced a time-dependent inhibition of JNK phosphorylation, which might suggest the Supplemental Material can be found at: ( 13,61 ). In this context, we and others have demonstrated that dietary supplementation with LA reduces weight loss and fat mass without increasing circulating FFA and improves insulin resistance in rodents ( 10,62,63 ) and in humans ( 7 ), and, as previously suggested, this could be associated with LA-induced fatty acid oxidation. In this context, our experimental data support the notion about the ability of LA to promote fatty acid oxidation in 3T3-L1 adipocytes (supplementary Fig.…”

supporting

confidence: 58%

Effects of lipoic acid on lipolysis in 3T3-L1 adipocytes

Fernández‐Galilea

Pérez-Matute

Prieto-Hontoria

et al. 2012

Journal of Lipid Research

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This article is available online at http://www.jlr.org properties. In fact, LA is able to directly scavenge reactive oxygen species (ROS) and regenerate endogenous antioxidants, such as glutathione and vitamins E and C ( 1, 2 ). Moreover, several studies have described potential beneficial effects of LA on obesity and its associated comorbidities, such as insulin resistance, type 2 diabetes, or fatty liver diseases. Thus, in rodents LA has been shown to cause profound weight loss by reducing food intake and enhancing energy expenditure ( 3 ) as well as by inducing a reduction on intestinal sugar absorption ( 4 ). More recently, two clinical trials in humans reported that LA caused signifi cant reductions of body weight, body mass index, blood pressure, and abdominal circumference in obese subjects ( 5, 6 ). LA also improved insulin sensitivity and plasma lipid profi le possibly through amelioration of oxidative stress and chronic infl ammatory status in obese patients with impaired glucose tolerance ( 7 ). Previous studies have provided strong evidence that LA is able to deeply affect adipose tissue development and function by the inhibition of adipogenesis ( 8 ), the regulation of the secretion of several adipokines such as leptin ( 9 ) and apelin ( 10 ), and by the promotion of mitochondrial biogenesis ( 11 ).In this context, previous studies suggested that LA seems to stimulate the lipolytic response in an in vitro model of broiler chicken adipocytes ( 12 ). However, the molecular mechanisms that mediate these effects remain unclear. Lipolysis is a complex process that is highly regulated and Lipoic acid (LA), or 1,2-dithiolane-3-pentaenoic acid, is a naturally occurring compound that contains two thiol groups with diverse benefi cial effects on health. The biological effects of LA were primarily associated with its antioxidant This work was supported, in part,

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supporting

confidence: 58%

Effects of lipoic acid on lipolysis in 3T3-L1 adipocytes

Fernández‐Galilea

Pérez-Matute

Prieto-Hontoria

et al. 2012

Journal of Lipid Research

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“…LA has powerful antioxidant properties and is therefore suitable for the treatment of diseases related to oxidative stress; for example, short-term and long-term supplementation of LA (200-1800 mg/day) in type 2 diabetic patients have beneficial effects in maintenance of glycemic control (200). LA can exert beneficial effects by several mechanisms, including improvement in vascular endothelial cell function (257), decrease in inflammation (104), amelioration of lipid abnormalities (376), and protection against myocardial ischemia/reperfusion injury (341) or antihypertensive effects (83). Defects in LA biosynthesis in human subjects can lead to the development of mitochondrial diseases, as has been shown in children with a mutation of NFU1, which is necessary for maturation of proteins such as succinate dehydrogenase or lipoic synthase (215).…”

Section: Non-targeted Antioxidant Treatmentsmentioning

confidence: 99%

Molecular Strategies for Targeting Antioxidants to Mitochondria: Therapeutic Implications

Apostolova

Víctor

2015

Antioxidants & Redox Signaling

234

147

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Mitochondrial function and specifically its implication in cellular redox/oxidative balance is fundamental in controlling the life and death of cells, and has been implicated in a wide range of human pathologies. In this context, mitochondrial therapeutics, particularly those involving mitochondria-targeted antioxidants, have attracted increasing interest as potentially effective therapies for several human diseases. For the past 10 years, great progress has been made in the development and functional testing of molecules that specifically target mitochondria, and there has been special focus on compounds with antioxidant properties. In this review, we will discuss several such strategies, including molecules conjugated with lipophilic cations (e.g., triphenylphosphonium) or rhodamine, conjugates of plant alkaloids, amino-acid-and peptide-based compounds, and liposomes. This area has several major challenges that need to be confronted. Apart from antioxidants and other redox active molecules, current research aims at developing compounds that are capable of modulating other mitochondria-controlled processes, such as apoptosis and autophagy. Multiple chemically different molecular strategies have been developed as delivery tools that offer broad opportunities for mitochondrial manipulation. Additional studies, and particularly in vivo approaches under physiologically relevant conditions, are necessary to confirm the clinical usefulness of these molecules. Antioxid. Redox Signal. 22, 686-729.

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“…LA has been used therapeutically in diabetic neuropathy and retinopathy (1, 6, 19, 33, 36, 38, 46, 49 -52), but its TG-lowering properties have only recently been recognized, first in laboratory animals (7,22,43,47) and then in humans (27,48). LA is a naturally occurring, essential, dithiol-containing cofactor synthesized enzymatically from octanoate in most prokaryotic and eukaryotic micro-organisms as well as plant and animal mitochondria (15).…”

mentioning

confidence: 99%

Characterization of genome-wide transcriptional changes in liver and adipose tissues of ZDF (fa/fa) rats fed R-α-lipoic acid by next-generation sequencing

Pashaj

Xia

et al. 2013

Physiological Genomics

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Pashaj A, Yi X, Xia M, Canny S, Riethoven JJM, Moreau R. Characterization of genome-wide transcriptional changes in liver and adipose tissues of ZDF (fa/fa) rats fed R-␣-lipoic acid by next-generation sequencing. Physiol Genomics 45: 1136 -1143. First published October 8, 2013 doi:10.1152/physiolgenomics.00138.2013.-We report on the characterization of lipogenic tissue transcriptional networks that support physiological responses of obese rats to a lipid-lowering bioactive food compound, R-␣-lipoic acid (LA). Nine-week-old male Zucker diabetic fatty (fa/fa) rats were fed a chow diet supplemented with 3 g LA per kg diet or pair fed for 2 wk. At the end of the trial, high-quality RNA was extracted from the liver and epididymal fat and subjected to transcriptome analysis by RNA-Seq technology. Results showed a substantially higher number of differentially expressed genes [DEG, false discovery rate adjusted P Յ 0.05 and absolute log 2 (fold change) Ն 1] in the liver (110 genes) vs. epididymal fat (10 genes). Most epididymal fat DEG were also differentially expressed in liver and shared directionality of change. Gene Ontology (GO) analysis of these transcripts revealed significant enrichment of GO categories related to immune response, stress response, lipid metabolism, and carboxylic acid metabolic processes. Of interest, interferonrelated genes involved in defense against microorganisms and innate immune response were induced by LA. Lipid metabolism-related transcript changes observed in LA-fed animals included downregulation of lipogenic genes (Pnpla3, Pnpla5, Elovl6, Acly, Gpam, and Aacs) and concomitant upregulation of short-, medium-, and longchain fatty acid metabolic processes (Acot1, Acot2, Acsf2, and Crat). Transcriptional changes were accompanied by the lowering of abdominal adiposity and blood triacylglycerol levels. We conclude that LA dietary supplementation induces prominent gene expression changes in liver in support of significant improvement of whole-body lipid status. dyslipidemia; nonalcoholic fatty liver disease; nutritional genomics OVERSTIMULATED LIPOGENESIS by a surplus of dietary fat and carbohydrate contributes to the early stages of numerous metabolic diseases, chief among them is nonalcoholic fatty liver disease (NAFLD). NAFLD, defined as the presence of macrovesicular steatosis in the liver of individuals ingesting Ͻ20 g of alcohol per day, is the most common liver disease in the US. Its prevalence is increasing worldwide in parallel with the increasing incidences of obesity and Type 2 diabetes. Several studies have documented a strong association between NAFLD and traditional and nontraditional risk factors for cardiovascular disease (CVD) (40, 41). Accordingly, patients with NAFLD have an increased prevalence and incidence of CVD (5, 26). It is believed that NAFLD and CVD share common risk factors, such as visceral obesity, insulin resistance, hyperglycemia, hypertension, and dyslipidemia. Consequently, the remediation of NAFLD is expected to positively impact the number and severity o...

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Amelioration of Lipid Abnormalities by α‐Lipoic acid Through Antioxidative and Anti‐Inflammatory Effects

Cited by 113 publications

References 40 publications

Effects of lipoic acid on lipolysis in 3T3-L1 adipocytes

Effects of lipoic acid on lipolysis in 3T3-L1 adipocytes

Molecular Strategies for Targeting Antioxidants to Mitochondria: Therapeutic Implications

Characterization of genome-wide transcriptional changes in liver and adipose tissues of ZDF (fa/fa) rats fed R-α-lipoic acid by next-generation sequencing

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