Leptin Receptor Immunoreactivity in Chemically Defined Target Neurons of the Hypothalamus

Abstract

The adipose tissue-derived hormone leptin regulates body weight homeostasis by decreasing food intake and increasing energy expenditure. The weight-reducing action of leptin is thought to be mediated primarily by signal transduction through the leptin receptor (LR) in the hypothalamus. We have used immunohistochemistry to localize LR-immunoreactive (LR-IR) cells in the rat brain using an antiserum against a portion of the intracellular domain of LR that is common to all LR isoforms. The antiserum recognized the short and long isoforms of LR in transfected hematopoietic BaF3 cells. To examine the chemical nature of target cells for leptin, direct double-labeling immunofluorescence histochemistry was applied. The results show extensive distribution of LR-like immunoreactivity (LR-LI) in the brain with positively stained cells present, e.g., in the choroid plexus, cerebral cortex, hippocampus, thalamus, and hypothalamus. In the hypothalamus, strongly LR-IR neurons were present in the supraoptic nucleus (SON) and paraventricular nucleus (PVN), periventricular nucleus, arcuate nucleus, and lateral hypothalamus. Weaker LR-IR neurons were also demonstrated in the lateral and medial preoptic nuclei, suprachiasmatic nucleus, ventromedial and dorsomedial nuclei, and tuberomammillary nucleus. Confocal laser scanning microscopy showed LR-LI in the periphery of individual cells. In magnocellular neurons of the SON and PVN, LR-LI was demonstrated in vasopressin-and oxytocin-containing neurons. In parvocellular neurons of the PVN, LR-LI was demonstrated in many corticotropin-releasing hormone-containing neurons. LR-IR neurons were mainly seen in the ventromedial aspect of the arcuate nucleus, where LR-LI co-localized with neuropeptide Y. In the ventrolateral part of the arcuate nucleus, LR-LI was present in many large adrenocorticotropic hormone-IR proopiomelanocortin-containing neurons and in a few galanin-, neurotensin-, and growth hormone-releasing hormonecontaining neurons. In the dorsomedial arcuate nucleus, few tyrosine hydroxylase (dopamine)-containing neurons were seen to have LR-LI. Melanin-concentrating hormone-containing neurons in the lateral hypothalamus had LR-LI. Based on the immunohistochemical results, possible interactions of leptin with brain mechanisms are discussed.

Delayed Satiety-Like Actions and Altered Feeding Microstructure by a Selective Type 2 Corticotropin-Releasing Factor Agonist in Rats: Intra-Hypothalamic Urocortin 3 Administration Reduces Food Intake by Prolonging the Post-Meal Interval

“…Interestingly, leptin appears to be both upstream and downstream of hypothalamic CRF 2 action, perhaps providing a physiological context for the current findings. Leptin has receptors on CRFergic hypothalamic neurons (Hakansson et al, 1998), provokes secretion of CRF receptor agonists from hypothalamic explants (Costa et al, 1997;Raber et al, 1997), and stimulates PVN CRF (Schwartz et al, 1996) and VMH CRF 2 mRNA synthesis (Hashimoto et al, 2004). Conversely, Zucker obese (fa/fa) rats, which lack a fully functional leptin receptor, have reduced VMH CRF 2 mRNA expression (Richard et al, 1996).…”

The Neuroanatomical Axis for Control of Energy Balance

“…Thus, CRH 2a -R mRNA, CRH mRNA, and peptide level are increased after icv leptin administration (132,145,192), and treatment with a CRH-R antagonist attenuates the intake suppression that otherwise follows icv leptin administration (64,188). The mediating mechanisms for these actions (with possibilities involving, for example, Ob-Rb on CRH neurons and projections to PVN from arcuate neurons containing POMC, CART, AgRP, and NPY (e.g., 85,42) are yet to be established.…”

Leptina: o diálogo entre adipócitos e neurônios

“…Uma forte presença da expressão do gene do receptor Ob-Rb é vista nos diversos núcleos hipotalâmicos que regulam a ingestão alimentar e o controle do gasto energético (28). Técnicas de imunohistoquímica localizaram a proteína do receptor também no hipotálamo (29). Além disso, leptina injetada dentro dos ventrículos cerebrais levou à expressão do fator de transcrição STAT3 e ativação neuronal em núcleos do hipotálamo (30).…”