Distribution Of Leptin Receptors Research Articles

Distribution of leptin receptors in the brain stem: possible route in the pathophysiology of neuromuscular control of airway resistance during sleep

IntroductionLeptin, a hormone related to satiety, has been studied because of its association with obesity and sleep apnea. The distribution of leptin receptors in the brain stem, and in the hypoglossal nucleus, has not yet been described. The stimulation of these muscles has been studied in the treatment of sleep apnea. Objectiveto detail the presence of leptin receptors in the nuclei of these nerves to enable studies of stimulation of this region through leptin. Methods: the brains of five cadavers, removed during necropsy, collected at the Death Verification Service were included. An informed consent was signed by a family member (wife, mother or son/daughter) who answered specific questionnaire concerning comorbities. Anthropometric measurements were recorded. The medulla oblongata and pons fragments were identified. Immunohistochemical staining analysis was performed to identify the location of the leptin receptors. ResultsIn the immunohistochemical analysis an intense staining signal of the brownish coloration of neurons was evidenced in the hypoglossal nerve nucleus, moderate in the olivary nucleus and mild in the dorsal nucleus of the vagus and trigeminal nucleus. In motor neurons, more intense brown pigmentation can be observed in the nucleus and cytoplasm when compared to sensory neurons. ConclusionThe immunoexpression of leptin receptor was demonstrated in the motor neurons of the human hypoglossal nucleus. These results may contribute to unravel details of the pathophysiology of neuromuscular control of airway collapse during sleep and to the development of new drugs capable of improving the neuromuscular tone of upper airway in apneic individuals.

The expression and distribution of a leptin receptor in the central nervous system, digestive organs, and gonads of the giant freshwater prawn, Macrobrachium rosenbergii

In the present study, the presence and distribution of leptin receptor (LEP-R) in central nervous system, digestive organs, gonads of giant freshwater prawn, Macrobrachium rosenbergii, were investigated with Western blot and immunohistochemistry. By Western blot a LEP-R with a molecular weight (MW) of 100 kDa was detected in the brain, thoracic ganglia, abdominal ganglia, hepatopancreas, all parts of the gastrointestinal tract, ovaries, and testes. In hepatopancreas and foregut, another intense positive band was detected at molecular weight of 30 kDa, which could be an isotype of LEP-R. By immunohistochemistry, LEP-R-ir was detected in the neurons, and neuropils in the brain, thoracic ganglia, and abdominal ganglia. In the gastrointestinal tract, there was intense LEP-R-ir in the apical part of the epithelial cells of the foregut, midgut, and hindgut. In addition, LEP-R-ir was found in the Restzellen(R)cells and Fibrillenzellen(F) cells in the hepatopancreas. In the ovary, LEP-R-ir was detected in early stage of oocytes and mature oocytes. Intense LEP-R-ir was observed in spermatogonia and spermatocytes of the small and orange claw male prawns. In addition, LEP-R was seen in the high epithelium of spermatic ducts from all male morphotypes. In summary, the detection of the LEP-R-ir suggests the existence of a LEP-R in several organs of M. rosenbergii. Through binding with leptin peptide, LEP-R may be an important signaling molecule that has critical functions in modulating and controlling food intake, energy expenditure, and reproduction in this prawn.

The leptin receptor is expressed in the Leydig cells of Merino rams, but its expression is not affected by long-term differences in the plane of nutrition

We studied whether the long-term effects of nutrition on ram reproductive potential are mediated by changes in the expression and distribution of leptin receptor (Ob-Rb) in the testes. Thirty-two young Merino rams were allocated to a 2 × 2 factorial design, with either natural (NP) or improved pastures (IP), with (+S) or without (–S) supplementation. After 14 weeks of treatment, a blood sample was taken to measure leptin concentrations and rams were castrated. The weights of testicles (TW) and epididymides (EW) were recorded before tissue sampling for the detection of Ob-Rb expression by immunohistochemistry. TW was positively affected by the interaction IP × S, but not EW and bodyweight (BW), which were affected either by IP or S (P < 0.05). TW and EW were greatest (g) in IP+S rams (290.6 ± 40.1 and 57.6 ± 2.3), followed by IP–S (284.6 ± 61.4 and 52.5 ± 2.3), NP+S (282.6 ± 37.9 and 55.8 ± 2.3), and NP–S rams (208.5 ± 48.7 and 44.4 ± 2.3; P < 0.01). Expression of Ob-Rb was observed in the cytoplasm of Leydig cells, without any effect of treatments on the percentage of positive Leydig cells or on staining-intensity score. The serum leptin concentrations were similar among groups. The absolute volume of the seminiferous epithelium (mL) was affected by IP and S, as well as by their interaction (IP–S: 179.7 ± 13.1, IP+S; 174.9 ± 9.0; NP+S: 178.0 ± 10.2; NP–S: 120.8 ± 9.8; P < 0.05). We conclude that, under the conditions of the present study, the long-term improvement of nutrition promoted histological changes of increased spermatogenesis of Merino rams, but was not related to changes in the expression of the Ob-Rb receptor in the Leydig cell cytoplasm.

Immunolocalization of leptin and its receptor in the pancreas of the horse

The aim of the present study was to demonstrate the presence and the distribution of leptin and its receptor in the pancreas of horses of both sexes by immunohistochemical techniques. The presence and the distribution of leptin receptor were also investigated in the initial portion of the duodenum, near the duodenal ampulla. The immunohistochemical investigation demonstrates the immunolocalization of both leptin and its receptor in the endocrine cells of pancreatic islets, which led us to hypothesize that leptin may possibly exert an autocrine/paracrine action on the endocrine pancreas. Examination of the exocrine pancreas in the same treated sections showed the presence of leptin-positive cells in the wall of the interlobular ducts where, however, the receptor was not found. This observation led us to consider that some cells of the ducts may perform some minimal secretory activity, and that leptin produced by these ductal cells may reach the duodenum in the pancreatic juice. This hypothesis is enhanced by the presence of leptin-receptor in the duodenum of the same animals, where the epithelial cells of the mucosa showed intense immunolocalization in the brush border. Consequently it is possible that the ductular leptin may play a regulatory role on the functionality of the enterocytes.

Leptin-signal transduction pathways and relationship with cancer development

Leptin is a versatile 16 kDa peptide hormone, with tertiary structure resembling that of members of the long-chain helical cytokine family. It is mainly produced by adipocytes in proportion to fat size stores, and was originally thought to act only as a satiety factor. However, the ubiquitous distribution of leptin receptors in almost all tissues underlies the pleiotropism of leptin. This review will focus on the link between leptin, a cytokine that is elevated in obese individuals, and cancer development through clarifying the intracellular signaling pathways of leptin. First, I discuss the biological functions of leptin and its signaling pathways. Then, I summarize the effects of leptin on different cancer types in experimental cellular and animal models. Next, I analyze the relationship between obesity and the presence of cancer or cancer risk in patients. Finally, leptin as a target for cancer treatment in the future and prevention will be discussed.

Immunohistochemical localization of leptin receptor in the rat brain

The distribution of leptin receptor in the rat brain was determined by immunocytochemistry and Western blotting. Strong leptin receptor immunoreactivity was detected in the arcuate, paraventricular and ventromedial nuclei of the hypothalamus, and lateral hypothalamic area. The olfactory bulb, neocortex, cerebellar cortex, dorsal raphe nucleus, inferior olive nucleus, nucleus of the solitary tract, dorsal motor nucleus of the vagus nerve also showed intense immunoreactivity. Western blotting analysis yielded a 120-kDa major band.

Leptin Induces Mitogen-activated Protein Kinase- dependent Proliferation of C3H10T1/2 Cells

Leptin, secreted by adipocytes, regulates satiety and energy expenditure. Several forms of leptin receptors produced by alternative mRNA splicing are found in many tissues, including the hypothalamus, liver, lung, kidney, hematopoietic cells, and gonads, suggesting that leptin exerts effects in these tissues. In accordance with the distribution of leptin receptors, there is accumulating evidence that leptin plays various roles in reproduction, hematopoiesis, and the immune systems in addition to the regulation of food intake and energy expenditure. In the present study, we examined the in vitro effects of leptin on proliferation of a mouse embryonic cell line, C3H10T1/2, and its mechanism of action. Leptin caused a dose- and time-dependent increase in mitogen-activated protein kinase (MAPK) activity that was accompanied by an increase in C3H10T1/2 cell number. The MAPK kinase-1-specific inhibitor PD98059 completely blocked the increases in both MAPK activity and cell proliferation caused by leptin. These findings indicate that leptin stimulates the proliferation of C3H10T1/2 cells via the MAPK cascade.