α-Lipoic acid prevents lipotoxic cardiomyopathy in acyl CoA-synthase transgenic mice

Lee, Young Ho; Naseem, R. Haris; Park, Byung Hyun; Garry, Daniel J.; Richardson, James A.; Schaffer, Jean E.; Unger, Roger H

doi:10.1016/j.bbrc.2006.03.062

Cited by 71 publications

(43 citation statements)

References 17 publications

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“…Adiposity directly damages the heart by promoting ectopic deposition of TG, a process known as myocardial steatosis. Cardiac steatosis can lead to dilated cardiomyopathy and an impaired cardiac function, so-called lipotoxic cardiomyopathy (31)(32)(33). Accordingly, cardiac functions were assessed by echocardiography in 55-wk-old OLETF rats.…”

Section: Thiamine Preserved Cardiac Function and Circumvented Interstmentioning

confidence: 99%

Thiamine Prevents Obesity and Obesity-Associated Metabolic Disorders in OLETF Rats

Tanaka

Kono

Terasaki

et al. 2010

J Nutr Sci Vitaminol

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SummaryWe previously found that thiamine mitigates metabolic disorders in spontaneously hypertensive rats, harboring defects in glucose and fatty acid metabolism. Mutation of thiamine transporter gene SLC19A2 is linked to type 2 diabetes mellitus. The current study extends our hypothesis that thiamine intervention may impact metabolic abnormalities in Otsuka Long-Evans Tokushima Fatty (OLETF) rats, exhibiting obesity and metabolic disorders similar to human metabolic syndrome. Male OLETF rats (4 wk old) were given free access to water containing either 0.2% or 0% of thiamine for 21 and 51 wk. At the end of treatment, blood parameters and cardiac functions were analyzed. After sacrifice, organs weights, histological findings, and hepatic pyruvate dehydrogenase (PDH) activity in the liver were evaluated. Thiamine intervention averted obesity and prevented metabolic disorders in OLETF rats which accompanied mitigation of reduced lipid oxidation and increased hepatic PDH activity. Histological evaluation revealed that thiamine alleviated adipocyte hypertrophy, steatosis in the liver, heart, and skeletal muscle, sinusoidal fibrosis with formation of basement membranes (called pseudocapillarization) which accompanied significantly reduced expression of laminin ␤ 1 and nidogen-1 mRNA, interstitial fibrosis in the heart and kidney, fatty degeneration in the pancreas, thickening of the basement membrane of the vasculature, and glomerulopathy and mononuclear cell infiltration in the kidney. Cardiac and renal functions were preserved in thiamine treatment. Thiamine has a potential to prevent obesity and metabolic disorders in OLETF rats.

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Section: Thiamine Preserved Cardiac Function and Circumvented Interstmentioning

confidence: 99%

Thiamine Prevents Obesity and Obesity-Associated Metabolic Disorders in OLETF Rats

Tanaka

Kono

Terasaki

et al. 2010

J Nutr Sci Vitaminol

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“…While these data suggest that dysregulation of adipocyte LCFA uptake might contribute to the pathogenesis of obesity, it is alternatively possible that the ability of adipocytes to upregulate LCFA uptake during caloric excess represents a buffer that protects hepatocytes, pancreatic b-cells, cardiac and skeletal muscle from LCFAmediated lipotoxicity. [10][11][12][13][14][15][16] Comparisons of obesity-prone and -resistant rodent strains are useful in studying the pathogenesis of obesity. C57BL/6J but not A/J mice, 17,18 and Osborne-Mendel (OM) but not S5B/Pl rats develop obesity when fed high-fat diets (HFDs).…”

Section: Introductionmentioning

confidence: 99%

Differences in adipocyte long chain fatty acid uptake in Osborne–Mendel and S5B/Pl rats in response to high-fat diets

et al. 2008

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Objective: To determine whether strain differences in adipocyte uptake of long chain fatty acids (LCFAs) contribute to differences in weight gain by Osborne-Mendel (OM) and S5B/Pl rats (S) fed a high-fat diet (HFD). Subjects: Ninety-four adult (12-14-week old) male OM and S rats. Measurements: Body weight; epididymal fat pad weight; adipocyte size, number, LCFA uptake kinetics; and plasma insulin and leptin during administration of HFD or chow diets (CDs). Results: In both strains, rate of weight gain (RWG) was greater on an HFD than a CD; RWG on an HFD was greater, overall, in OM than S. A significant RWG increase occurred on days 1 and 2 in both strains. It was normalized in S by days 6-9 but persisted at least till day 14 in OM. RWGs were significantly correlated (Po0.001) with the V max for saturable adipocyte LCFA uptake (V max ). In S, an increase in V max on day 1 returned to baseline by day 7 and was correlated with both plasma insulin and leptin levels throughout. In OM, a greater increase in V max was evident by day 2, and persisted for at least 14 days, during which both insulin and leptin levels remained elevated. Growth in epididymal fat pads on the HFD correlated with body weight, reflecting hypertrophy in OM and both hypertrophy and hyperplasia in S. Conclusions: (a) Changes in V max contribute significantly to changes in RWG on HFDs. (b) There are important strain differences in circulating insulin and leptin responses to an HFD. (c) Both insulin and leptin responses to an HFD are closely correlated with V max of adipocyte fatty acid uptake in S animals, but suggest early onset of insulin resistance in OM. Thus, differences in hormonal regulation of adipocyte LCFA uptake may underlie the different responses of OM and S to HFD.

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“…[14][15][16][17] The importance of oxidative stress in the pathophysiological response to substrate excess is underscored by observation that treatment with chemical antioxidants and overexpression of ROS-scavenging enzymes mitigates against lipotoxic cell death and against diabetic complications in animal models. [18][19][20][21] To identify critical mediators of lipotoxic cell death, our laboratory has focused on characterizing genes identified through a loss-of-function genetic screen in mammalian fibroblasts. We found that cells become resistant to death from lipotoxic and generalized oxidative stress stimuli upon disruption of small nucleolar RNAs (snoRNAs) encoded within the ribosomal protein L13a (rpL13a) locus or disruption of expression of a splicosomal protein necessary for production of these non-coding RNAs from intron lariats.…”

mentioning

confidence: 99%

RNASET2 is required for ROS propagation during oxidative stress-mediated cell death

et al. 2015

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RNASET2 is a ubiquitously expressed acidic ribonuclease that has been implicated in diverse pathophysiological processes including tumorigeneis, vitiligo, asthenozoospermia, and neurodegeneration. Prior studies indicate that RNASET2 is induced in response to oxidative stress and that overexpression of RNASET2 sensitizes cells to reactive oxygen species (ROS)-induced cell death through a mechanism that is independent of catalytic activity. Herein, we report a loss-of-function genetic screen that identified RNASET2 as an essential gene for lipotoxic cell death. Haploinsufficiency of RNASET2 confers increased antioxidant capacity and generalized resistance to oxidative stress-mediated cell death in cultured cells. This function is critically dependent on catalytic activity. Furthermore, knockdown of RNASET2 in the Drosophila fat body confers increased survival in the setting of oxidative stress inducers. Together, these findings demonstrate that RNASET2 regulates antioxidant tone and is required for physiological ROS responses.

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α-Lipoic acid prevents lipotoxic cardiomyopathy in acyl CoA-synthase transgenic mice

Cited by 71 publications

References 17 publications

Thiamine Prevents Obesity and Obesity-Associated Metabolic Disorders in OLETF Rats

Thiamine Prevents Obesity and Obesity-Associated Metabolic Disorders in OLETF Rats

Differences in adipocyte long chain fatty acid uptake in Osborne–Mendel and S5B/Pl rats in response to high-fat diets

RNASET2 is required for ROS propagation during oxidative stress-mediated cell death

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