Induction of Leptin Expression in Orbital Preadipocyte Fibroblasts

Erickson, Dana; Harteneck, Debra A.; Erickson, Bradley J.; Dutton, Charyl M.; Bahn, Rebecca S.

doi:10.1089/105072501750159570

Cited by 15 publications

(10 citation statements)

References 18 publications

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“…We have also previously demonstrated nuclear localization of leptin IR in C6 glioblastoma cells [50]. In an unrelated study of preadipocyte fibroblasts [51], leptin IR was also clearly cytoplasmic and perinuclear, consistent with our findings in some neurons, for example in the hippocampus, where staining was predominantly perinuclear.…”

Section: Discussionsupporting

confidence: 90%

Leptin Immunoreactivity Is Localized to Neurons in Rat Brain

Ur¹,

Wilkinson²,

Morash³

et al. 2002

Neuroendocrinology

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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.

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Section: Discussionsupporting

confidence: 90%

Leptin Immunoreactivity Is Localized to Neurons in Rat Brain

Ur¹,

Wilkinson²,

Morash³

et al. 2002

Neuroendocrinology

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“…Preadipocytes are able to evolve in mature adipose cells, modifying their gene expression profile (20,21,22). The concept that adipose cells might express TSHr was formulated in 1964 by Rodbell (23) who demonstrated TSH stimulated lipolysis in rat epididymal cells showing for the first time extrathyroidal expression of the TSHr.…”

Section: Discussionmentioning

confidence: 99%

Evidence for protein and mRNA TSHr expression in fibroblasts from patients with thyroid-associated ophthalmopathy (TAO) after adipocytic differentiation

et al. 2005

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Objective: Thyroid-associated ophthalmopathy (TAO) is a chronic autoimmune disorder characterized by an increased volume of adipose/connective tissue in the human orbit. Design: The aim of this study was to investigate the thyrotropin receptor (TSHr) expression in orbital fibroblasts from TAO patients undergoing adipocytic differentiation. Methods: Retro-ocular tissue and skin were obtained from five patients undergoing orbital decompression surgery for TAO and placed in culture. Proliferating fibroblasts were subjected to adipocytic differentiation for 10 days. Total RNA was isolated from fibroblasts and was reverse transcribed. TSHr mRNA levels were determined by real-time PCR. cAMP was determined by radioimmunoassay (RIA) after fibroblast incubation with the substances to test. Results: Orbital differentiated fibroblasts became rounded and acquired lipid droplets. The amount of TSHr mRNA in these fibroblasts was higher than fibroblasts not subjected to adipocytic differentiation. Immunocytochemical analysis showed TSHr protein in differentiated orbital fibroblasts. Differentiated orbital fibroblasts stimulated with bovine (b) TSH showed a cAMP production greater than that in paired undifferentiated cultures. A specific thyroid-inhibiting antibody (TBAb) inhibited cAMP production after bTSH challenge, and a thyroid-stimulating antibody (TSAb) stimulated cAMP production in differentiated fibroblasts. Conclusions: We suggest that orbital fibroblasts subjected to adipocytic differentiation increase TSHr expression that responds specifically to bTSH and TSAb stimulation, and to TBAb inhibition. European Journal of Endocrinology 152 777-784

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“…Ozata et al (70) further divided the patients with Graves' disease into those with and those without thyroid associated ophthalmopathy (TAO), based on the theory that human preadipocyte fibroblasts in orbital connective tissues from patients with TAO differentiate into cells resembling adipocytes and acquire expression of leptin and functional TSH receptors (91). Mean leptin levels were similar in all the groups compared both to matched controls and to each other (70).…”

Section: Human Studiesmentioning

confidence: 99%

Circulating leptin and thyroid dysfunction

Zimmermann-Belsing

Brabant²,

Holst³

et al. 2003

Eur J Endocrinol

151

111

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The identification and sequencing of the ob gene and its product, leptin, in 1994 opened new insights in the study of the mechanisms controlling body weight and led to a surge of research activity. Since its discovery, leptin has been the subject of an enormous amount of work especially within the fields of nutrition, metabolism and endocrinology. Leptin is accepted as an adipose signal, and even though the underlying mechanisms are not fully clarified, leptin, in addition to the thyroid hormones, is believed to be involved in regulation during the switch from the fed to the starved state. It is not clear whether leptin and the melanocortin pathways interact with the thyroid axis under physiological conditions other than during starvation or in response to severe illness, both states in which the hypothalamo -pituitary -thyroid axis may be severely suppressed. In addition to the suggested central relationship between leptin and thyroid hormones, there might also be a peripheral relationship although this effect is not clear. Both thyroid hormones and leptin might be involved in the adaptive thermogenesis through mitochondrial uncoupling proteins and heat production because both thyroxine and triiodothyronine are involved in the starvation-induced decrease in thermogenesis. Both rodent and human studies of leptin have failed to show any consistent relationship between thyroid function and serum leptin concentrations. However, leptin might have an important role in thyroid pathophysiology due to thyroid hormone involvement in thermogenesis and regulation of uncoupling proteins. In this review, we have focused on leptin in relation to thyroid pathophysiology.

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Induction of Leptin Expression in Orbital Preadipocyte Fibroblasts

Cited by 15 publications

References 18 publications

Leptin Immunoreactivity Is Localized to Neurons in Rat Brain

Leptin Immunoreactivity Is Localized to Neurons in Rat Brain

Evidence for protein and mRNA TSHr expression in fibroblasts from patients with thyroid-associated ophthalmopathy (TAO) after adipocytic differentiation

Circulating leptin and thyroid dysfunction

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