A study of the ameliorating effects of carnitine on hepatic steatosis induced by total parenteral nutrition in rats

Liu, Liang

doi:10.3748/wjg.v5.i4.312

Cited by 15 publications

(6 citation statements)

References 8 publications

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“…The data herein indicate that l ‐car supplementation of the SRS cocktail was critical for macrosteatotic hepatocyte defatting and improved resistance to H/R stress under hyperoxic (90% O 2 ) conditions. The defatting effect of l ‐car is consistent with studies showing that the administration of l ‐car as a nutritional supplement to dieting patients with nonalcoholic steatohepatitis or to rats with steatotic livers reduced hepatic steatosis and TG levels . Although a large body of literature describes the ability of l ‐car supplementation to promote FFA oxidation, l ‐car may have contributed in other ways to the increase in hepatocyte resistance to H/R stress.…”

Section: Discussionsupporting

confidence: 81%

“…The defatting effect of L-car is consistent with studies showing that the administration of L-car as a nutritional supplement to dieting patients with nonalcoholic steatohepatitis or to rats with steatotic livers reduced hepatic steatosis and TG levels. 28,29 Although a large body of literature describes the ability of L-car supplementation to promote FFA oxidation, 16,17,19,30 L-car may have contributed in other ways to the increase in hepatocyte resistance to H/R stress. For example, the addition of L-car to a cold preservation solution for 24 hours was reported to increase ATP levels in steatotic rat livers.…”

Section: Discussionmentioning

confidence: 99%

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Elevated sensitivity of macrosteatotic hepatocytes to hypoxia/reoxygenation stress is reversed by a novel defatting protocol

Nativ

Yarmush

et al. 2014

Liver Transpl

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Macrosteatotic livers exhibit elevated intrahepatic triglyceride (TG) content in the form of large lipid droplets (LDs), reduced ATP, and elevated reactive oxygen species (ROS), contributing to their elevated sensitivity to ischemia-reperfusion injury during transplantation. Decreasing macrosteatosis in living donors through dieting has been shown to improve transplantation outcome. Accomplishing the same feat in deceased donor grafts would require ex-vivo exposure to potent defatting agents. Herein, we used a rat hepatocyte culture system exhibiting macrosteatotic LD morphology, elevated TG levels, and elevated sensitivity to hypoxia and reoxygenation (H/R), to test for such agents and ameliorate H/R sensitivity. Macrosteatotic hepatocyte preconditioning for 48h with a defatting cocktail, previously developed to promote TG catabolism, reduced the number of macrosteatotic LDs and intracellular TG levels by 82% and 27%, respectively, but did not ameliorate sensitivity to H/R. L-carnitine supplementation to this cocktail, together with hyperoxic exposure, yielded a similar reduction in macrosteatotic LD numbers, and to a 57% reduction in intrahepatic TG storage, likely by increasing the supply of acetyl-CoA to mitochondria, as indicated by a 70% increase in ketone body secretion. Furthermore, this treatment reduced ROS levels by 32%, increased ATP levels by 27%, nearing ATP levels of lean controls, and completely abolished H/R sensitivity as indicated by ~85% viability post H/R and return of cytosolic lactate dehydrogenase release down to levels seen in lean controls. Cultures maintained for 48h post H/R were ~83% viable and exhibited superior urea secretion and bile canalicular transport compared to untreated macrosteatotic cultures. These findings show that the elevated sensitivity of macrosteatotic hepatocytes to H/R can be overcome by defatting agents, suggesting a possible route for the recovery of discarded macrosteatotic grafts.

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Section: Discussionsupporting

confidence: 81%

Section: Discussionmentioning

confidence: 99%

Elevated sensitivity of macrosteatotic hepatocytes to hypoxia/reoxygenation stress is reversed by a novel defatting protocol

Nativ

Yarmush

et al. 2014

Liver Transpl

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“…Most studies on PepT1 have focused on its fundamental kinetic properties and its functional and structural characterization [19][20][21] . Previous studies have shown that the functions of intestine (including PepT1) were changed under the influence of many factors [22,23] . However, few reports have dealt with the hormonal regulation of PepT1.…”

Section: Discussionmentioning

confidence: 99%

Changes of biological functions of dipeptide transporter (PepT1) and hormonal regulation in severe scald rats

Sun

Zhao²,

Wang³

et al. 2003

WJG

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“…In addition, L-carnitine was shown to improve glucose tolerance and insulin sensitivity in animals as well as in healthy and diabetic patients [ 12 , 13 ]. Moreover, L-carnitine supplementation was shown to be useful for the treatment of hepatic steatosis induced by total parenteral nutrition in rodents [ 14 ] and nonalcoholic steatohepatitis in humans [ 15 , 16 ]. Furthermore, L-carnitine was reported to reduce hepatic inflammation and plasma levels of cytokines and acute phase proteins in patients with chronic hepatitis C [ 16 ].…”

Section: Introductionmentioning

confidence: 99%

Effect of L-carnitine on the hepatic transcript profile in piglets as animal model

et al. 2011

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BackgroundCarnitine has attracted scientific interest due to several health-related effects, like protection against neurodegeneration, mitochondrial decay, and oxidative stress as well as improvement of glucose tolerance and insulin sensitivity. The mechanisms underlying most of the health-related effects of carnitine are largely unknown.MethodsTo gain insight into mechanisms through which carnitine exerts its beneficial metabolic effects, we fed piglets either a control or a carnitine supplemented diet, and analysed the transcriptome in the liver.ResultsTranscript profiling revealed 563 genes to be differentially expressed in liver by carnitine supplementation. Clustering analysis of the identified genes revealed that most of the top-ranked annotation term clusters were dealing with metabolic processes. Representative genes of these clusters which were significantly up-regulated by carnitine were involved in cellular fatty acid uptake, fatty acid activation, fatty acid β-oxidation, glucose uptake, and glycolysis. In contrast, genes involved in gluconeogenesis were down-regulated by carnitine. Moreover, clustering analysis identified genes involved in the insulin signaling cascade to be significantly associated with carnitine supplementation. Furthermore, clustering analysis revealed that biological processes dealing with posttranscriptional RNA processing were significantly associated with carnitine supplementation.ConclusionThe data suggest that carnitine supplementation has beneficial effects on lipid and glucose homeostasis by inducing genes involved in fatty acid catabolism and glycolysis and repressing genes involved in gluconeogenesis.

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A study of the ameliorating effects of carnitine on hepatic steatosis induced by total parenteral nutrition in rats

Cited by 15 publications

References 8 publications

Elevated sensitivity of macrosteatotic hepatocytes to hypoxia/reoxygenation stress is reversed by a novel defatting protocol

Elevated sensitivity of macrosteatotic hepatocytes to hypoxia/reoxygenation stress is reversed by a novel defatting protocol

Changes of biological functions of dipeptide transporter (PepT1) and hormonal regulation in severe scald rats

Effect of L-carnitine on the hepatic transcript profile in piglets as animal model

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