Decreased blood–brain leptin transfer in an ovine model of obesity and weight loss: resolving the cause of leptin resistance

Adam, Carole; Findlay, P.A.

doi:10.1038/ijo.2010.28

Cited by 42 publications

(37 citation statements)

References 27 publications

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“…Prolonged reductions of leptin levels during CR might then be anticipated to reverse the state of leptin resistance and make CR animals' leptin sensitive. In sheep (Ovis aeries) this does not appear to be the case (Adam and Findlay, 2010). The ratio between endogenous leptin concentrations in ventricular cerebrospinal fluid (CSF) and peripheral blood decreased with increasing leptin levels in the blood, in obese sheep, indicating decreased efficiency of blood-brain leptin transport.…”

Section: Leptin and Other Adipokinesmentioning

confidence: 94%

Caloric restriction

Speakman

Mitchell

2011

Molecular Aspects of Medicine

673

675

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Section: Leptin and Other Adipokinesmentioning

confidence: 94%

Caloric restriction

Speakman

Mitchell

2011

Molecular Aspects of Medicine

673

675

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“…16 It likely results from defects in the hypothalamic neural circuitry that regulates energy homeostasis 16 and/or in leptin transport into the brain. 17 The supposed action of leptin on liver hepcidin production is a typical peripheral action that should not be affected by the mechanisms producing central leptin resistance.…”

Section: Discussionmentioning

confidence: 99%

Effect of body mass index reduction on serum hepcidin levels and iron status in obese children

et al. 2010

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Iron deficiency has been linked to obesity. Hepcidin is the main regulator of iron homeostasis and is higher in obese children compared to controls. To gain insight into the link between obesity and hepcidin, we performed an intervention study in 15 obese children. These children were subjected to a 6-month weight loss program and underwent physical examination and iron status and absorption as well as hepcidin, interleukin-6 and leptin serum levels evaluation at baseline and after the weight loss program. After the program all children reduced their body mass index standard deviation score (BMI SDS) of at least 0.5. We observed a significant decrease in hepcidin (P ¼ 0.003) and leptin levels (P ¼ 0.005), and a significant increase in iron absorption (P ¼ 0.02). A direct correlation between the measure of hepcidin and leptin reduction was observed and this correlation appeared significant (r 2 ¼ 0.33, P ¼ 0.003) when adjusted for interleukin-6 and BMI SDS variations. In conclusion, we have shown that, in obese children, BMI reduction is associated with hepcidin reduction, potentially improving iron status and absorption. Implications of these findings could be considered in the management of obese children with poor iron status.

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“…Seasonal changes in the photoperiod regulate mood-related behavior and physiology in mammals, including humans [37]. Adam and Findlay [38] emphasized that sheep provide a valuable model to study the neuroendocrine aspects of the transfer of most circulating factors across the bloodbrain barrier. The easy access to CSF in large animals as opposed to rodents is clearly advantageous.…”

Section: Discussionmentioning

confidence: 99%

Photoperiod Influences the Effects of Ghrelin and Serotonin Receptor Agonist on Growth Hormone and Prolactin Secretion in Sheep

Zieba¹,

Kirsz²,

Szczesna³

et al. 2015

J Neurol Neurophysiol

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Objective: Recent studies have identified a novel heterodimer involving the ghrelin receptor (GHS-R1A) and the 5-HT2C receptor, a subtype of serotonin receptors. Whether or not interactions between GHS-R1A and the 5-HT2C receptor exist and how they are modulated by photoperiod and nutritional status in seasonally animals remains unknown. The aims of this study were to determine the effects of ghrelin and a 5-HT2B/2C serotonin receptor agonist, 1-(3-chlorophenyl) piperazine hydrochloride (m-CPP), on GH and PRL secretion under the influence of nutritional status and photoperiod.Methods: Normally fed (n=12) or fasted (n=12) ewes were assigned to one of 4 groups and treatments: 1) control (saline); 2) ghrelin (2.5 μg/kg); 3) m-CPP (2.5 mg/kg); 4) ghrelin followed by m-CPP were infused once at the beginning of the study for groups 1, 2 and 3; in group 4, ghrelin was administered at 15 min, and m-CPP at 30 min. Blood samples were collected at 15-min intervals for 3 h during the short day (SD) and long day (LD) season.Results: Ghrelin and m-CPP enhanced (p<0.05) GH secretion in fasted ewes during LD. The m-CPP significantly decreased GH concentrations in fasted ewes during SD. Prolactin concentrations were lower (p<0.01) in normally fed ewes after the ghrelin + m-CPP treatment compared to treatment with m-CPP alone. Conclusion:There were interactions among ghrelin, serotonin, photoperiod and metabolic status that influenced GH and PRL secretion in ewes. Using an ovine model, our work provides a basis for future studies of the pathogenesis of metabolic disorders associated with alterations in nutritional status and day length.

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Decreased blood–brain leptin transfer in an ovine model of obesity and weight loss: resolving the cause of leptin resistance

Cited by 42 publications

References 27 publications

Caloric restriction

Caloric restriction

Effect of body mass index reduction on serum hepcidin levels and iron status in obese children

Photoperiod Influences the Effects of Ghrelin and Serotonin Receptor Agonist on Growth Hormone and Prolactin Secretion in Sheep

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