Leptin and Ob-Rb Receptor Isoform in the Human Digestive Tract during Fetal Development

Aparicio, Thomas; Kermorgant, Stéphanie; Darmoul, Dalila; Guilmeau, Sandra; Hormi, Khadija; Michelet, Dominique; Lehy, Thérèse

doi:10.1210/jc.2005-1498

Cited by 45 publications

(35 citation statements)

References 47 publications

(69 reference statements)

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“…19,20 Beside its important role in the normal physiology of the gastrointestinal tract, the trophic effects of leptin on the small intestinal mucosa have been demonstrated in certain gastrointestinal disorders. 21,22 In recent studies, we have demonstrated the positive effect of leptin on intestinal recovery following intestinal ischemia-reperfusion 11 and on gut re-growth following massive small bowel resection in a rat model.…”

Section: Methodsmentioning

confidence: 99%

Leptin accelerates enterocyte turnover during methotrexate-induced intestinal mucositis in a rat model

Sukhotnik

Shteinberg

Karry

et al. 2009

Cancer Biology & Therapy

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Gastrointestinal mucositis occurs as a consequence of cytotoxic treatment. In the present study, we tested whether leptin can protect gut epithelial cells from methotrexate (MTX)-induced intestinal damage. Non-pretreated and pretreated with MTX Caco-2 cells were incubated with increasing concentrations of leptin for 24 h. Cell proliferation and apoptosis were assessed using FACS analysis. Adult rats were divided into three experimental groups: Control rats; MTX-rats were treated with a single dose of MTX, and MTX-LEP rats were also treated with leptin for 3 d. Intestinal mucosal damage (Park score), mucosal structural changes (bowel and mucosal weight, mucosal DNA and protein content, villus height and crypt depth), enterocyte proliferation, and enterocyte apoptosis were measured at sacrifice. RT-PCR was used to determine the level of bax and bcl-2 mRNA expression. In the vitro experiment, treatment with leptin of Caco-2 cells pre-treated with MTX resulted in a significant stimulation of cell proliferation and inhibition of cell apoptosis in a dose-dependent manner. In the vivo experiment, MTX-LEP rats demonstrated a greater jejunal and ileal bowel and mucosal weight, mucosal DNA and protein, villus height and crypt depth, as well as a greater enterocyte proliferation index compared to MTX-animals. MTX-LEP rats also showed a trend toward an increase in enterocyte apoptosis that was accompanied by an increase in bax mRNA and decrease in bcl-2 mRNA expression. In conclusion, leptin enhances proliferation and decreases apoptosis in Caco-2 cells pretreated with MTX. In a rat model of MTX-induced mucositis, treatment with leptin improves intestinal recovery and enhances enterocyte turnover.

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Section: Methodsmentioning

confidence: 99%

Leptin accelerates enterocyte turnover during methotrexate-induced intestinal mucositis in a rat model

Sukhotnik

Shteinberg

Karry

et al. 2009

Cancer Biology & Therapy

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“…During fetal development, locally produced leptin appears to regulate the growth and/or maturation of the digestive tract (Aparicio et al 2005a). Postnatally, leptin modulates local immune responses, and has been shown to exert either pro-or anti-inflammatory activities in the intestine, depending on the experimental model (Siegmund et al 2002, Bozkurt et al 2003, Cakir et al 2004, Sitaraman et al 2004, Adeyemi et al 2005, Karagiannides & Pothoulakis 2007.…”

Section: Introductionmentioning

confidence: 99%

Obesity hormone leptin induces growth and interferes with the cytotoxic effects of 5-fluorouracil in colorectal tumor stem cells

Bartucci¹,

Svensson²,

Ricci–Vitiani³

et al. 2010

Endocrine-Related Cancer

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The incidence of colon cancer has increased in developed countries, possibly due to sedentary lifestyle and high caloric diet. Experimental and epidemiological evidence suggests a link between colon cancer development and adipose tissue-derived circulating hormones. Leptin, a pluripotent cytokine secreted by adipocytes, is a key regulator of appetite and energy balance acting in the brain. On the other hand, leptin also controls many physiological and pathological processes in peripheral organs. Recent studies in colon cancer cell lines and human tumors suggested that leptin and its receptor (ObR) are implicated in colon carcinogenesis, and may serve as new biomarkers and pharmacological targets. Here, we explored, for the first time, whether leptin can affect the biology of colorectal tumor stem cells (CTSCs). We found that our previously established and characterized CTSC clones express ObR and respond to leptin with cell proliferation, activation of the extracellular signal-related kinase (ERK)1/2 and AKT signaling pathways, enhanced growth in soft agar, and improved sphere formation associated with E-cadherin overexpression. Moreover, leptin counteracted cytotoxic effects of 5-fluorouracil, a common colon cancer therapeutic agent. These results suggest that obesity and increased leptin levels might promote colorectal cancer by increasing growth and survival of CTSCs.

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“…The presence of leptin immunopositivity in the oesophageal epithelium of bony fish has not yet been reported, but we suggested that leptin could be involved in the oesophageal functions and particularly in mucous secretion. We also hypothesised that leptin distribution is more extensive during development than in adults as reported in human foetuses (Aparicio et al 2005).…”

Section: Discussionmentioning

confidence: 88%

Immunolocalisation of leptin in the digestive system of juvenile European sea bass (Dicentrarchus labrax)

Gambardella

Ferrando

et al. 2010

Italian Journal of Zoology

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Leptin is a hormone that is mainly produced by adipocytes; it is connected with metabolism regulation, but knowledge about its effect on teleosts, particularly in juvenile specimens, is still scarce. This study is the first to investigate the presence of leptin immunoreactivity in juvenile European sea bass (Dicentrarchus labrax) and its distribution in the digestive system. Leptin immunoreactivity was detected by Western blot analysis, while its distribution was obtained using immunohistochemical methods with a human leptin-specific antibody. The homogenate of the body of a whole European sea bass contains a leptin-like protein with an estimated molecular weight of approximately 16 kDa. Leptin immunoreactivity was distributed along the digestive system, especially in the oesophageal mucous cells, neuroendocrine gastrointestinal cells and eosinophilic granular cells of the gastrointestinal lamina propria. This is the first report on leptin immunoreactivity in juvenile sea bass and our data can provide a good morphological basis for further investigation into food, metabolism and immunoresponse regulation in aquacultured fish.

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Leptin and Ob-Rb Receptor Isoform in the Human Digestive Tract during Fetal Development

Cited by 45 publications

References 47 publications

Leptin accelerates enterocyte turnover during methotrexate-induced intestinal mucositis in a rat model

Leptin accelerates enterocyte turnover during methotrexate-induced intestinal mucositis in a rat model

Obesity hormone leptin induces growth and interferes with the cytotoxic effects of 5-fluorouracil in colorectal tumor stem cells

Immunolocalisation of leptin in the digestive system of juvenile European sea bass (Dicentrarchus labrax)

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