Leptin Immunoreactivity Is Localized to Neurons in Rat Brain

Abstract

Leptin is secreted from adipocytes and is thought to enter the brain to regulate and coordinate metabolism, feeding behaviour, energy balance and reproduction. It is now clear that there are many additional sites of leptin production, including human placenta, ovary, stomach, skeletal muscle, mammary gland, pituitary gland and brain. In the present work, we employed double-label immunofluorescent histochemistry to establish the neuronal localization of leptin immunoreactivity (IR). To accomplish this, we used the neuron-specific marker NeuN to label cells in the arcuate nucleus (ARC), piriform cortex and hippocampus. In the supraoptic nucleus (SON) and paraventricular nucleus (PVN), we used antisera to oxytocin and vasopressin as neuronal markers. Double labelling revealed leptin IR in neurons of the ARC and piriform cortex. Leptin IR was confined to the nucleus and to distinct perinuclear sites. In contrast, neurons in the CA 2/CA 3 region of the hippocampus showed little nuclear staining. Leptin IR was clustered around the nucleus in these cells. Neurons of the dentate gyrus exhibited both nuclear and perinuclear localization of leptin IR. In the SON/PVN, most oxytocin- and vasopressin-IR neurons also contained leptin IR, often in perinuclear sites. In conclusion, the neuronal, perinuclear localization of leptin IR in rat brain corresponds closely to that of leptin receptor (OB-R) IR, which has also been detected intracellularly. Our observation of leptin IR associated with cell nuclei suggests the existence of an OB-R distinct from the well-described membrane forms.

Serum leptin level is a regulator of bone mass

“…For instance, it has been difficult to date to correlate bone density, an indirect assessment of bone mass, and serum leptin level in humans (13)(14)(15). Moreover, leptin antiosteogenic action was more easily achieved by ICV infusion than by peripheral injection, and lastly, leptin expression has been detected by RT-PCR and immunocytochemistry in the mouse hypothalamus (16), where leptin antiosteogenic neurons reside (2). Together, these observations suggested the possibility that leptin was produced locally in the brain and that this local production was important in understanding leptin antiosteogenic function.…”

JAK-STAT pathway in carcinogenesis: Is it relevant to cholangiocarcinoma progression?

“…Appearance of components of JAK-STAT signaling in the nucleus or the enrichment of their nuclear pool seems to be associated with their participation in the regulation of proliferative processes and may be related to cholangiocarcinoma progression. Ligands (such as Prl, GH, leptin, IL-1, IL-5, IFN-γ, TGF-α) and receptors acting via the JAK-STAT pathway or associated with STAT signaling by other mechanisms have been found in the nuclear compartment of different cell types mainly under conditions of high proliferative status and cancer development [8,10,[166][167][168][169] .…”

Does leptin play a cytokine-like role within the airways of COPD patients?

“…Leptin, the product of the ob gene, is a pleiotropic molecule which regulates food intake and some metabolic and endocrine functions. Demonstrations have shown it to be secreted by adipose tissue [2], gastric mucosa [3], intestinal epithelial cells [4], placenta, mammary epithelium and skeletal muscle [5]. The leptinreceptor is expressed in peripheral tissues and cells, including: kidney, lung, adrenal gland, haematopoietic precursor cells and bone marrow, neutrophils, monocytes and peripheral T cells [6].…”