Expression of leptin and leptin receptor isoforms in the human stomach

Mix, Heiko; Widjaja, A.; Jandl, Oliver; Cornberg, Markus; Kaul, Alina; Göke, Michael; Beil, Winfried; Kuske, Marvin; Brabant, Georg; Manns, Michael P.; Wagner, Siegfried

doi:10.1136/gut.47.4.481

Cited by 167 publications

(112 citation statements)

References 29 publications

(10 reference statements)

Supporting

Mentioning

102

Contrasting

Unclassified

Order By: Relevance

“…13,20 There is evidence indicating that feeding stimulates the secretion of leptin by the stomach in humans 12,13 and in rats, 11,21 and pepsinogen secretagogues such as cholecystokinin (CCK), gastrin or secretin also induce gastric leptin release in rats. 11 Leptin receptors are present in the human stomach [22][23][24] and in the mouse gastrointestinal tract, 25 and additionally leptin is capable of direct and acute activation of vagal afferent neurons that originate in the gastric and intestinal walls and terminate in the nucleus tractus solitarius, 26 providing rapid information to the brain.…”

Section: Introductionmentioning

confidence: 99%

The intake of physiological doses of leptin during lactation in rats prevents obesity in later life

et al. 2007

View full text Add to dashboard Cite

Ciber Fisiopatología obesidad y nutrición (CB06/03) Instituto Salud Carlos III, SpainBackground: There is epidemiological evidence that perinatal nutritional factors may have long-term effects on obesity. Which nutrients or food components are involved in this programming mechanism are unknown. Breast milk contains leptin, a hormone that regulates food intake and energy expenditure, and previous studies in rats have shown that leptin orally administered during lactation exerts anorexigenic effects. Objective: To evaluate whether supplementation with physiological doses of oral leptin during lactation has long-term effects on body weight regulation. Design: A daily oral dose of leptin (equivalent to five times the amount of leptin ingested normally from maternal milk during the suckling period) or the vehicle was given to suckling male rats during lactation. Animals were fed after weaning with a normal fat (NF) or a high-fat (HF) diet. We followed body weight and food intake of animals until the age of 6 months, and measured the size of adipose tissue depots, the thermogenic capacity, the expression of leptin in the stomach and adipose tissues and the expression of two appetite-related peptides (neuropeptide Y (NPY) and proopiomelanocortin (POMC)), leptin receptor (OB-Rb) and suppressor of cytokine signalling 3 (SOCS-3) in the hypothalamus at the age of 6 months. Results: Leptin-treated animals had, in adulthood, lower body weight and fat content and ate fewer calories than their untreated controls. Unlike adipocitary leptin production, adult animals that were leptin-treated during lactation displayed higher gastric leptin production without changes in OB-Rb mRNA levels. In addition, in response to HF diet, leptin-treated animals (contrary to controls) showed lower hypothalamic NPY/POMC mRNA ratio. Hypothalamic OB-Rb mRNA levels decreased in control animals as an effect of HF diet feeding, but remained unchanged in leptin-treated animals; SOCS-3 mRNA levels were lower in leptin-treated animals than in their controls, both under normal or HF diet. Conclusion: The animals that received leptin during lactation become more protected against fat accumulation in adult life and seem to be more sensitive to the short-and long-term regulation of food intake by leptin. Thus, leptin plays an important role in the earlier stages of neonatal life, as a component of breast milk, in the prevention of later obesity.

show abstract

Section: Introductionmentioning

confidence: 99%

The intake of physiological doses of leptin during lactation in rats prevents obesity in later life

et al. 2007

View full text Add to dashboard Cite

show abstract

“…Ob-R is highly expressed in the hypothalamus but is also found in many peripheral tissues. For example, Ob-R is detected in normal gastric mucosa, especially in chief cells and parietal cells, and in some gastric cancer cells (3,4). Furthermore, in addition to adipocytes and the placenta, the gastric mucosa has been shown to produce a significant amount of leptin (5).…”

Section: Introductionmentioning

confidence: 99%

Transactivation of Epidermal Growth Factor Receptor Is Involved in Leptin-Induced Activation of Janus-Activated Kinase 2 and Extracellular Signal–Regulated Kinase 1/2 in Human Gastric Cancer Cells

et al. 2005

View full text Add to dashboard Cite

Leptin is known to act as a growth factor through the Janusactivated kinase (JAK)/signal transducer and activator of transcription signaling pathway as well as the mitogenactivated protein kinase pathway. In this study, we showed a novel signal transduction pathway using two human gastric cancer cell lines, MKN28 and MKN74. Both gastric cancer cells expressed leptin and its receptors (Ob-R) at the protein level. We found that leptin, even at as low as 0.1 ng/mL, induced significant tyrosine phosphorylation of epidermal growth factor receptor (EGFR). Time-course experiments revealed that phosphorylation was maximal after 5 minutes of stimulation and declined thereafter. We also revealed that tyrosine phosphorylation of EGFR induced by leptin was significantly attenuated by two inhibitors, an EGFR tyrosine kinase inhibitor, AG1478, and a broad-spectrum matrix metalloproteinase inhibitor, GM6001. This indicates that the pathway of EGFR transactivation induced by leptin is dependent on proteolytically released EGFR ligands. Leptin induced JAK2 activation and extracellular signal-regulated kinase (ERK) 1/2 activation in these gastric cancer cells, both of which occurred after the peak of EGFR transactivation. Pretreatment of gastric cancer cells with AG1478 significantly reduced the degree of phosphorylation of both JAK2 and ERK1/2. These findings indicate the involvement of EGFR transactivation in the activation of JAK2 and ERK1/2. Our results reveal that EGFR transactivation is involved in the leptin signaling pathway in gastric cancer cells, which extends the physiologic action of leptin beyond its central effects in the hypothalamus to regulate body weight. (Cancer Res 2005; 65(20): 9159-63)

show abstract

“…The transcriptional regulation of the leptin gene was described as being controlled by Peroxisome proliferator-activated receptor-gamma (PPAR-g) [6][7][8], and down-regulated by adrenergic stimulation [9]. Although described as an adipocyte-derived hormone, leptin is also secreted by several other cell types [7,10]. We have recently shown an in vitro leptin expression that was enhanced by glucocorticoids in mesenchymal synovial fibroblasts (SVF) [11].…”

mentioning

confidence: 99%

“…Leptin was widely studied in 3T3-L1 mouse cell line described as having the potential to differentiate into adipocytes, but with a low level of leptin mRNA expression [4,5]. The transcriptional regulation of the leptin gene was described as being controlled by Peroxisome proliferator-activated receptor-gamma (PPAR-g) [6][7][8], and down-regulated by adrenergic stimulation [9]. Although described as an adipocyte-derived hormone, leptin is also secreted by several other cell types [7,10].…”

mentioning

confidence: 99%

Differential Signalling Through ALK-1 and ALK-5 Regulates Leptin Expression in Mesenchymal Stem Cells

Zeddou¹,

Relić

Malaise

et al. 2012

Stem Cells and Development

View full text Add to dashboard Cite

Leptin plays a central role in maintaining energy balance, with multiple other systemic effects. Despite leptin importance in peripheral regulation of mesenchymal stem cells (MSC) differentiation, little is known about its expression mechanism. Leptin is often described as adipokine, while it is expressed by other cell types. We have recently shown an in vitro leptin expression, enhanced by glucocorticoids in synovial fibroblasts (SVF). Here, we investigated leptin expression in MSC from bone marrow (BM-MSC) and umbilical cord matrix (UMSC). Results showed that BM-MSC, but not UMSC, expressed leptin that was strongly enhanced by glucocorticoids. Transforming growth factor b1 (TGF-b1) markedly inhibited the endogenous-and glucocorticoid-induced leptin expression in BM-MSC. Since TGF-b1 was shown to signal via ALK-5-Smad2/3 and/or ALK-1-Smad1/5 pathways, we analyzed the expression of proteins from both pathways. In BM-MSC, TGF-b1 increased phosphorylated Smad2 (p-Smad2) expression, while ALK-5 inhibitor (SB431542) induced leptin expression and significantly restored TGF-b1-induced leptin inhibition. In addition, both prednisolone and SB431542 increased p-Smad1/5 expression. These results suggested the ALK-5-Smad2 pathway as an inhibitor of leptin expression, while ALK-1-Smad1/5 as an activator. Indeed, Smad1 expression silencing induced leptin expression inhibition. Furthermore, prednisolone enhanced the expression of TGF-bRII while decreasing p-Smad2 in BM-MSC and SVF but not in UMSC. In vitro differentiation revealed differential osteogenic potential in SVF, BM-MSC, and UMSC that was correlated to their leptin expression potential. Our results suggest that ALK-1/ALK-5 balance regulates leptin expression in MSC. It also underlines UMSC as leptin nonproducer MSC for cell therapy protocols where leptin expression is not suitable.

show abstract

Expression of leptin and leptin receptor isoforms in the human stomach

Cited by 167 publications

References 29 publications

The intake of physiological doses of leptin during lactation in rats prevents obesity in later life

The intake of physiological doses of leptin during lactation in rats prevents obesity in later life

Transactivation of Epidermal Growth Factor Receptor Is Involved in Leptin-Induced Activation of Janus-Activated Kinase 2 and Extracellular Signal–Regulated Kinase 1/2 in Human Gastric Cancer Cells

Differential Signalling Through ALK-1 and ALK-5 Regulates Leptin Expression in Mesenchymal Stem Cells

Contact Info

Product

Resources

About