Leptin increases mitotic index and regeneration ratio in hepatectomized rats

Çilekar, Murat; Uysal, Onur Kadir; Bal, Cengiz; Türel, Serkan; Yılmaz, Sezgin

doi:10.12659/msmbr.889591

Cited by 10 publications

(9 citation statements)

References 18 publications

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“…Furthermore, the administration of intraperitoneal leptin before a partial hepatectomy in Sprague Dawley rats shift to an increase of mitosis rate, regeneration ratio, and final liver weight, besides improving histopathological damage [ 275 ]. On the other hand, C57BL/6 mice subjected to a western diet for six weeks to induce simple steatosis present an improvement of hepatic regeneration after partial hepatectomy that correlates with the increase of the leptin presence in serum among other signaling factors [ 276 ].…”

Section: Leptin Role In the Liver Regeneration Processmentioning

confidence: 99%

Unraveling the Role of Leptin in Liver Function and Its Relationship with Liver Diseases

Martínez-Uña

López-Mancheño

Diéguez

et al. 2020

IJMS

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Since its discovery twenty-five years ago, the fat-derived hormone leptin has provided a revolutionary framework for studying the physiological role of adipose tissue as an endocrine organ. Leptin exerts pleiotropic effects on many metabolic pathways and is tightly connected with the liver, the major player in systemic metabolism. As a consequence, understanding the metabolic and hormonal interplay between the liver and adipose tissue could provide us with new therapeutic targets for some chronic liver diseases, an increasing problem worldwide. In this review, we assess relevant literature regarding the main metabolic effects of leptin on the liver, by direct regulation or through the central nervous system (CNS). We draw special attention to the contribution of leptin to the non-alcoholic fatty liver disease (NAFLD) pathogenesis and its progression to more advanced stages of the disease as non-alcoholic steatohepatitis (NASH). Likewise, we describe the contribution of leptin to the liver regeneration process after partial hepatectomy, the mainstay of treatment for certain hepatic malignant tumors.

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Section: Leptin Role In the Liver Regeneration Processmentioning

confidence: 99%

Unraveling the Role of Leptin in Liver Function and Its Relationship with Liver Diseases

Martínez-Uña

López-Mancheño

Diéguez

et al. 2020

IJMS

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“…A number of genes have been found to be strongly upregulated after tail amputation. One of them, leptin , is upregulated early after amputation to promote organ/tissue regeneration in different animal species [ 24 , 67 – 69 ]. Its upregulation was much lower in the wild type tail compared to TRDKO tail at 6 h after amputation at stage 61.…”

Section: Discussionmentioning

confidence: 99%

Thyroid hormone receptor knockout prevents the loss of Xenopus tail regeneration capacity at metamorphic climax

Wang

Shibata

et al. 2023

Cell Biosci

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Background Animal regeneration is the natural process of replacing or restoring damaged or missing cells, tissues, organs, and even entire body to full function. Studies in mammals have revealed that many organs lose regenerative ability soon after birth when thyroid hormone (T3) level is high. This suggests that T3 play an important role in organ regeneration. Intriguingly, plasma T3 level peaks during amphibian metamorphosis, which is very similar to postembryonic development in humans. In addition, many organs, such as heart and tail, also lose their regenerative ability during metamorphosis. These make frogs as a good model to address how the organs gradually lose their regenerative ability during development and what roles T3 may play in this. Early tail regeneration studies have been done mainly in the tetraploid Xenopus laevis (X. laevis), which is difficult for gene knockout studies. Here we use the highly related but diploid anuran X. tropicalis to investigate the role of T3 signaling in tail regeneration with gene knockout approaches. Results We discovered that X. tropicalis tadpoles could regenerate their tail from premetamorphic stages up to the climax stage 59 then lose regenerative capacity as tail resorption begins, just like what observed for X. laevis. To test the hypothesis that T3-induced metamorphic program inhibits tail regeneration, we used TR double knockout (TRDKO) tadpoles lacking both TRα and TRβ, the only two receptor genes in vertebrates, for tail regeneration studies. Our results showed that TRs were not necessary for tail regeneration at all stages. However, unlike wild type tadpoles, TRDKO tadpoles retained regenerative capacity at the climax stages 60/61, likely in part by increasing apoptosis at the early regenerative period and enhancing subsequent cell proliferation. In addition, TRDKO animals had higher levels of amputation-induced expression of many genes implicated to be important for tail regeneration, compared to the non-regenerative wild type tadpoles at stage 61. Finally, the high level of apoptosis in the remaining uncut portion of the tail as wild type tadpoles undergo tail resorption after stage 61 appeared to also contribute to the loss of regenerative ability. Conclusions Our findings for the first time revealed an evolutionary conservation in the loss of tail regeneration capacity at metamorphic climax between X. laevis and X. tropicalis. Our studies with molecular and genetic approaches demonstrated that TR-mediated, T3-induced gene regulation program is responsible not only for tail resorption but also for the loss of tail regeneration capacity. Further studies by using the model should uncover how T3 modulates the regenerative outcome and offer potential new avenues for regenerative medicines toward human patients.

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“…The liver, which is the largest organ of the human body, has great potential for regeneration, and the underlying mechanism of liver regeneration has received much attention [ 43 – 45 ]. The significant induction of miR-21 during liver regeneration has previously been reported in a murine model of partial hepatectomy (PH) [ 22 – 24 ].…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-21 Contributes to Liver Regeneration by Targeting PTEN

et al. 2016

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BackgroundMultiple microRNAs (miRNAs, miRs), including miR-21, have been documented to be critical regulators of liver regeneration, but the mechanism underlying their roles in hepatocyte proliferation and cell cycle progression is still far from understood.Material/MethodsmiR-21 levels were determined using qRT-PCRs in mouse livers at 48 h after 70% partial hepatectomy (PH-48 h). Cell proliferation was determined by use of a cell-counting kit-8 (CCK-8), EdU incorporation staining, and flow cytometry. Phosphatase and tensin homolog (PTEN) expressions were determined using qRT-PCR and Western blot analysis. PTEN siRNA was used to perform the rescue experiment.ResultsA marked upregulation of miR-21 was observed in mouse livers at 48 h after 70% partial hepatectomy (PH-48 h) compared to 0 h after PH (PH-0 h). Overexpression of miR-21 was associated with increased proliferation and a rapid G1-to-S phase transition of the cell cycle in BNL CL.2 normal liver cells in vitro. In addition, we showed that PTEN expression was inversely correlated with miR-21 in BNL CL.2 cells and demonstrated that PTEN expression is lower in mouse livers at PH-48 h. Moreover, the presence of PTEN siRNA significantly abolished the suppressive effect of miR-21 inhibitor on hepatocyte proliferation.ConclusionsmiR-21 overexpression contributes to liver regeneration and hepatocyte proliferation by targeting PTEN. Upregulation of miR-21 might be a useful therapeutic strategy to promote liver regeneration.

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Leptin increases mitotic index and regeneration ratio in hepatectomized rats

Cited by 10 publications

References 18 publications

Unraveling the Role of Leptin in Liver Function and Its Relationship with Liver Diseases

Unraveling the Role of Leptin in Liver Function and Its Relationship with Liver Diseases

Thyroid hormone receptor knockout prevents the loss of Xenopus tail regeneration capacity at metamorphic climax

MicroRNA-21 Contributes to Liver Regeneration by Targeting PTEN

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