Fatty acid transporters involved in the palmitate and oleate induced insulin resistance in primary rat hepatocytes

Chabowski, Adrian; Żendzian-Piotrowska, Małgorzata; Konstantynowicz, Karolina; Pankiewicz, Walentyn; Mikłosz, Agnieszka; Łukaszuk, Bartłomiej; Górski, Jan

doi:10.1111/apha.12022

Cited by 62 publications

(58 citation statements)

References 61 publications

(116 reference statements)

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“…Furthermore, it was clear that the largest decrease in sCD36 occurred among the children who improved insulin sensitivity and resolved fatty liver. These findings support the presumed relationship between CD36 and ectopic fat accumulation, as well as the development of insulin resistance, [12][13][14][15] and thus the importance of CD36 in obesity-related complications. 9,18 The fact that sCD36 decreased with weight loss and improvement in metabolic aberrations is in accordance with a study of weight loss induced by bariatric surgery in adults.…”

Section: Discussionsupporting

confidence: 78%

“…In case of fatty acid overload, this uptake contributes to ectopic fat accumulation and insulin resistance, in muscle, fat and liver cells, respectively. [12][13][14][15] In addition, CD36 is involved in the inflammatory responses in both adipocytes and macrophages in diet-induced obesity. 16 Recently, a circulating non-cell-bound form of CD36 (sCD36) was identified and proposed to reflect tissue CD36 expression.…”

Section: Introductionmentioning

confidence: 99%

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Reduced sCD36 following weight loss corresponds to improved insulin sensitivity, dyslipidemia and liver fat in obese children

et al. 2016

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Section: Discussionsupporting

confidence: 78%

Section: Introductionmentioning

confidence: 99%

Reduced sCD36 following weight loss corresponds to improved insulin sensitivity, dyslipidemia and liver fat in obese children

et al. 2016

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“…Although the uptake of fatty acids into the liver is at least in part regulated by fatty acid transporters, there is a correlation between liver and plasma concentrations of fatty acids [22,23]. The treatment of hepatocytes with NEFA such as palmitate inhibits insulin-mediated Akt phosphorylation and downstream signalling pathways including GSK-3β and forkhead box protein O1 [24].…”

Section: Discussionmentioning

confidence: 99%

Involvement of sphingosine 1-phosphate in palmitate-induced insulin resistance of hepatocytes via the S1P2 receptor subtype

et al. 2013

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Aims/hypothesis Enhanced plasma levels of NEFA have been shown to induce hepatic insulin resistance, which contributes to the development of type 2 diabetes. Indeed, sphingolipids can be formed via a de novo pathway from the saturated fatty acid palmitate and the amino acid serine. Besides ceramides, sphingosine 1-phosphate (S1P) has been identified as a major bioactive lipid mediator. Therefore, our aim was to investigate the generation and function of S1P in hepatic insulin resistance. Methods The incorporation of palmitate into sphingolipids was performed by rapid-resolution liquid chromatography-MS/MS in primary human and rat hepatocytes. The influence of S1P and the involvement of S1P receptors in hepatic insulin resistance was examined in human and rat hepatocytes, as well as in New Zealand obese (NZO) mice. Results Palmitate induced an impressive formation of extraand intracellular S1P in rat and human hepatocytes. An elevation of hepatic S1P levels was observed in NZO mice fed a high-fat diet. Once generated, S1P was able, similarly to palmitate, to counteract insulin signalling. The inhibitory effect of S1P was abolished in the presence of the S1P 2 receptor antagonist JTE-013 both in vitro and in vivo. In agreement with this, the immunomodulator FTY720-phosphate, which binds to all S1P receptors except S1P 2 , was not able to inhibit insulin signalling. Conclusions/interpretation These data indicate that palmitate is metabolised by hepatocytes to S1P, which acts via stimulation of the S1P 2 receptor to impair insulin signalling. In particular, S1P 2 inhibition could be considered as a novel therapeutic target for the treatment of insulin resistance.

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“…Routine Western blotting procedure was applied to detect proteins expression in myocardial plasma membranes, low density microsomes and mitochondria as it was described previously [22]. In all samples protein concentration was determined by using the bicinchonic acid method (BCA) with BSA as a standard.…”

Section: Immunoblottingmentioning

confidence: 99%

Myocardial Lipid Profiling During Time Course of High Fat Diet and its Relationship to the Expression of Fatty Acid Transporters

Harasim

Stepek

Konstantynowicz-Nowicka

et al. 2015

Cell Physiol Biochem

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Background/Aims: It is well documented that increased fatty acids (FA) supply causes lipid accumulation and insulin resistance in skeletal muscles. Whether the same mechanism is present in the heart is still unclear. Therefore, the goal of our study was to determine the content of specific myocardial lipid fractions during feeding rats a high fat diet (HFD) for 5 weeks. Moreover, the relation between changes in myocardial lipid content, whole body insulin resistance and the expression of fatty acid transporters in each week of HFD was established. Methods: Gas liquid chromatography and high performance liquid chromatography were used to determine the content of lipid fractions in the left ventricle. Expression of selected proteins was estimated by Western blot technique. All measurements were made after each week of HFD. Results: As expected, lipid profile in myocardium was altered by HFD in different weeks of the study with the most intense changes in triacylglycerols, long chain fatty acid-CoA and ceramide. Furthermore, there was a significant elevation of plasmalemmal (the 4^th and the 5^th week) and mitochondrial expression (from the 3^rd to the 5^th week) of fatty acid translocase. Conclusion: High fat diet affects myocardial lipid profile in each week of its duration and causes alternations in FA metabolism in cardiomyocytes.

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Fatty acid transporters involved in the palmitate and oleate induced insulin resistance in primary rat hepatocytes

Cited by 62 publications

References 61 publications

Reduced sCD36 following weight loss corresponds to improved insulin sensitivity, dyslipidemia and liver fat in obese children

Reduced sCD36 following weight loss corresponds to improved insulin sensitivity, dyslipidemia and liver fat in obese children

Involvement of sphingosine 1-phosphate in palmitate-induced insulin resistance of hepatocytes via the S1P2 receptor subtype

Myocardial Lipid Profiling During Time Course of High Fat Diet and its Relationship to the Expression of Fatty Acid Transporters

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