ArticleThe Journal of biological chemistry2009
Reduced intestinal absorption of dipeptides via PepT1 in mice with diet-induced obesity is associated with leptin receptor down-regulation.
Article in The Journal of biological chemistry, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 45 citations in OpenAlex.
- Regulation of Glucose Insulinotropic Peptide and Intestinal Glucose Transporters in the Diet-Induced Obese Mouse.Journal of diabetes research · 2022Article
- JAK2 Mediates the Regulation of Pept1 Expression by Leptin in the Grass Carp (Frontiers in physiology · 2020Article
- Function, Regulation, and Pathophysiological Relevance of the POT Superfamily, Specifically PepT1 in Inflammatory Bowel Disease.Comprehensive Physiology · 2018Review
- Physiological and therapeutic regulation of glucose homeostasis by upper small intestinal PepT1-mediated protein sensing.Nature communications · 2018Article
- Association between polymorphisms inDiabetes, metabolic syndrome and obesity : targets and therapy · 2018Article
- Fermented goat milk consumption during anaemia recovery: ergogenic effect and improvement of skeletal muscle homeostasis.European journal of nutrition · 2017Article
- MicroRNA-193a-3p Reduces Intestinal Inflammation in Response to Microbiota via Down-regulation of Colonic PepT1.The Journal of biological chemistry · 2015Article
- Modulation of intestinal L-glutamate transport by luminal leptin.Journal of physiology and biochemistry · 2015Article
- Glucose-dependent insulinotropic polypeptide-mediated signaling pathways enhance apical PepT1 expression in intestinal epithelial cells.American journal of physiology. Gastrointestinal and liver physiology · 2015Article
- Overexpression of gastric leptin precedes adipocyte leptin during high-fat diet and is linked to 5HT-containing enterochromaffin cells.International journal of obesity (2005) · 2014Article
- Large litter rearing improves leptin sensitivity and hypothalamic appetite markers in offspring of rat dams fed high-fat diet during pregnancy and lactation.Endocrinology · 2014Article
- Recent advances in small bowel diseases: Part II.World journal of gastroenterology · 2012Review
- Diverse roles of leptin in the gastrointestinal tract: modulation of motility, absorption, growth, and inflammation.Nutrition (Burbank, Los Angeles County, Calif.) · 2011Review
- The intestinal peptide transporter PEPT1 is involved in food intake regulation in mice fed a high-protein diet.PloS one · 2011Article
- Large litter rearing enhances leptin sensitivity and protects selectively bred diet-induced obese rats from becoming obese.Endocrinology · 2010Article
- Clock is important for food and circadian regulation of macronutrient absorption in mice.Journal of lipid research · 2009Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Leptin is a major determinant of energy homeostasis, acting both centrally and in the gastrointestinal tract. We previously reported that acute leptin treatment enhances the absorption of di- and tripeptides via the proton-dependent PepT1 transporter. In this study, we investigated the long term effect of leptin on PepT1 levels and activity in Caco2 cell monolayers in vitro. We then assessed the significance of the regulation of PepT1 in vivo in a model of diet-induced obesity. We demonstrated that 1) leptin regulated PepT1 at the transcriptional level, via the MAPK pathway, and at the translational level, via ribosomal protein S6 activation, in Caco2 cells and 2) this activation was systematically followed by a time- and concentration-dependent loss of leptin action reflecting desensitization. Deciphering this desensitization, we demonstrated that leptin induced a down-regulation of its own receptor protein and mRNA expression. More importantly, we showed, in mice with diet-induced obesity, that a 4-week hypercaloric diet resulted in a 46% decrease in PepT1-specific transport, because of a 30% decrease in PepT1 protein and a 50% decrease in PepT1 mRNA levels. As shown in Caco2 cells, these changes in PepT1 were supported by a parallel 2-fold decrease in leptin receptor expression in mice. Taken together, these results indicate that during induction of obesity, leptin resistance may also occur peripherally in the gastrointestinal tract, disrupting the absorption of oligopeptides and peptidomimetic drugs.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.