Central Administration of the Ciliary Neurotrophic Factor Analogue, Axokine, Does Not Play a Role in Long-Term Energy Homeostasis in Adult Mice

2015 ◽  
Vol 103 (3-4) ◽  
pp. 223-229 ◽  
Author(s):  
Melissa L. Borg ◽  
Alex Reichenbach ◽  
Moyra Lemus ◽  
Brian J. Oldfield ◽  
Zane B. Andrews ◽  
...  
2012 ◽  
Vol 302 (4) ◽  
pp. E458-E467 ◽  
Author(s):  
Odile Couvreur ◽  
Alain Aubourg ◽  
Delphine Crépin ◽  
Jéril Degrouard ◽  
Arieh Gertler ◽  
...  

Ciliary neurotrophic factor (CNTF) is a neural cytokine that reduces appetite and body weight when administrated to rodents or humans. We have demonstrated recently that the level of CNTF in the arcuate nucleus (ARC), a key hypothalamic region involved in food intake regulation, is positively correlated with protection against diet-induced obesity. However, the comprehension of the physiological significance of neural CNTF action was still incomplete because CNTF lacks a signal peptide and thus may not be secreted by the classical exocytosis pathways. Knowing that CNTF distribution shares similarities with that of its receptor subunits in the rat ARC, we hypothesized that CNTF could exert a direct intracrine effect in ARC cells. Here, we demonstrate that CNTF, together with its receptor subunits, translocates to the cell nucleus of anorexigenic POMC neurons in the rat ARC. Furthermore, the stimulation of hypothalamic nuclear fractions with CNTF induces the phosphorylation of several signaling proteins, including Akt, as well as the transcription of the POMC gene. These data strongly suggest that intracellular CNTF may directly modulate POMC gene expression via the activation of receptors localized in the cell nucleus, providing a novel plausible mechanism of CNTF action in regulating energy homeostasis.


2008 ◽  
Vol 28 (9) ◽  
pp. 2231-2241 ◽  
Author(s):  
P. Yang ◽  
S. A. Arnold ◽  
A. Habas ◽  
M. Hetman ◽  
T. Hagg

1989 ◽  
Vol 108 (5) ◽  
pp. 1807-1816 ◽  
Author(s):  
S Saadat ◽  
M Sendtner ◽  
H Rohrer

Ciliary neurotrophic factor (CNTF) influences the levels of choline acetyltransferase (ChAT) and tyrosine hydroxylase (TH) in cultures of dissociated sympathetic neurons from newborn rats. In the presence of CNTF both the total and specific activity of ChAT was increased 7 d after culture by 15- and 18-fold, respectively, as compared to cultures kept in the absence of CNTF. Between 3 and 21 d in culture in the presence of CNTF the total ChAT activity increased by a factor of greater than 100. Immunotitration demonstrated that the elevated ChAT levels were due to an increased number of enzyme molecules. In contrast to the increase in ChAT levels, the total and specific activity levels of TH were decreased by 42 and 36%, respectively, after 7 d in culture. Half-maximal effects for both ChAT increase and TH decrease were obtained at CNTF concentrations of approximately 0.6 ng and maximal levels were reached at 1 ng of CNTF per milliliter of medium. The effect of CNTF on TH and ChAT levels were seen in serum-containing medium as well as in serum-free medium. CNTF was shown to have only a small effect on the long-term survival of rat sympathetic neurons. We therefore concluded that the effects of CNTF on ChAT and TH are not due to selective survival of cells that acquire cholinergic traits in vitro, but are rather due to the induction of cholinergic differentiation of noradrenergic sympathetic neurons.


Diabetes ◽  
2010 ◽  
Vol 59 (4) ◽  
pp. 894-906 ◽  
Author(s):  
A. S. Reed ◽  
E. K. Unger ◽  
L. E. Olofsson ◽  
M. L. Piper ◽  
M. G. Myers ◽  
...  

2015 ◽  
Vol 7 (1) ◽  
Author(s):  
Gul Tiryaki-Sonmez ◽  
Serife Vatansever ◽  
Burcin Olcucu ◽  
Brad Schoenfeld

SummaryObesity, a disorder of body composition, is defined by a relative or absolute excess of body fat. In general adult population, obesity has been associated with a diverse array of adverse health outcomes, including major causes of death such as cancer, diabetes, cardiovascular disease, as well as functional impairment from problems such as osteoarthritis and sleep apnea. Ghrelin is a newly discovered peptide hormone which plays an important role in obesity. It is a powerful, endogenous orexigenic peptide and has a crucial function in appetite regulation, as well as short – and long-term energy homeostasis. In the presence of increased obesity, decreased physical activity, and high food consumption, the relationship between exercise, appetite, food intake and ghrelin levels has important implications. In this review, we discuss the effect of acute and chronic exercise performance on appetite, food intake and ghrelin and their relationships.


Endocrinology ◽  
2021 ◽  
Author(s):  
Judith Estrada-Meza ◽  
Jasmine Videlo ◽  
Clara Bron ◽  
Cécile Saint-Béat ◽  
Marine Silva ◽  
...  

Abstract Tamoxifen is a selective estrogen receptor modulator used to activate the CRE ERT2 recombinase, allowing tissue-specific and temporal control of the somatic mutagenesis to generate transgenic mice. Studies integrating development and metabolism require a genetic modification induced by a neonatal tamoxifen administration. Here, we investigate the effects of a neonatal tamoxifen administration on energy homeostasis in adult male and female C57BL/6J mice. C57BL/6J male and female mouse pups received a single injection of tamoxifen one day after birth (NTT) and were fed a high-fat/high-sucrose (HF/HS) diet at 6 weeks of age. We measured weight, body composition, glucose and insulin tolerance, basal metabolism and tibia length and weight in adult mice. The neonatal tamoxifen administration exerted long-term, sex-dependent effects on energy homeostasis. NTT female mice became overweight and developed impaired glucose control in comparison to vehicle-treated littermates. NTT females exhibited 60% increased fat mass, increased food intake, decreased physical activity and decreased energy expenditure, impaired glucose and insulin tolerance, and fasting hyperglycemia and hyperinsulinemia. In contrast, NTT male mice exhibited a modest amelioration of glucose and insulin tolerance, and long-term decreased lean mass linked to decreased bone weight. These results suggest that the neonatal tamoxifen administration exerted a marked and sex-dependent influence on adult energy homeostasis and bone weight, and must therefore be used with caution for the development of transgenic mouse models regarding studies on energy homeostasis and bone biology.


2004 ◽  
Vol 185 (1) ◽  
pp. 26-35 ◽  
Author(s):  
Diana Zala ◽  
Jean-Charles Bensadoun ◽  
Luis Pereira de Almeida ◽  
Blair R. Leavitt ◽  
Claire-Anne Gutekunst ◽  
...  

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