Leptin Prevents Respiratory Depression in Obesity

O’Donnell, Christopher P.; Schaub, C. D.; Haines, Abby; Berkowitz, Dan E.; Tankersley, Clarke G.; Schwartz, Alan R.; Smith, Philip L.

doi:10.1164/ajrccm.159.5.9809025

Cited by 352 publications

(283 citation statements)

References 26 publications

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“…For example, leptin has been postulated to mediate OSA susceptibility via effects on ventilatory drive. 21 Variability in adipokine levels has been found to closely aggregate within families, and linkage studies have identified potential genetic risk factors regulating the levels of each of the adipokines assessed in this study. [22][23][24] The significant estimates of heritability we calculated for levels of leptin, adiponectin and resistin also support an important genetic basis for these adipokines.…”

Section: Discussionmentioning

confidence: 80%

Shared genetic basis for obstructive sleep apnea and adiposity measures

2008

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Introduction: Obesity and obstructive sleep apnea each have a substantial genetic basis and commonly coexist in individuals. The degree to which the genetic underpinnings for these disorders overlap has not been previously quantified. Methods: A total of 1802 individuals from 310 families in the Cleveland Family Study underwent home sleep studies as well as standardized assessment of body mass index (BMI) and circumferences at the waist, hip and neck. In 713 participants with laboratory sleep studies, fasting blood samples were assayed for leptin, adiponectin and resistin. Variance component models were used to estimate heritability and genetic correlations. Results: The heritability of the apnea hypopnea index (AHI) was 0.37 ± 0.04 and 0.33 ± 0.07 for home and laboratory sleep studies, respectively. The genetic correlations between AHI and anthropomorphic adiposity measures ranged from 0.57 to 0.61, suggesting that obesity can explain nearly 40% of the genetic variance in sleep apnea. The magnitude of the genetic correlations between apnea severity and adipokine levels was substantially less than those with anthropomorphic measures, ranging from 0.11 to 0.46. After adjusting for BMI, no significant genetic correlation with apnea severity was observed for any of the other adiposity measures. Conclusions: Substantial but not complete overlap in genetic bases exists between sleep apnea and anthropomorphic indices of adiposity, and this overlap accounts for more than one-third of the genetic variance in apnea severity. These findings suggest that genetic polymorphisms exist that importantly influence sleep apnea susceptibility through both obesity-dependent and -independent pathways.

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Section: Discussionmentioning

confidence: 80%

Shared genetic basis for obstructive sleep apnea and adiposity measures

2008

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“…With respect to mice that were leptin receptor deficient due to genetic mutation, Tsuchiya et al (1999) reported that the rate of tracheal epithelial cell proliferation was only one-quarter (P , 0.01) that of their unaffected littermates, illustrating a potentially important supplementary role for leptin in pulmonary development. Other studies further suggest a significant impact of leptin on general pulmonary health in rodents (O'Donnell et al 1999), as well as on specific respiratory disorders in humans (O'Donnell et al 2000). Intriguingly, obesity-related respiratory anomalies are characteristically exacerbated in males (Kapsimalis & Kryger 2002), perhaps reflecting again the gender dichotomy that is typical with respect to circulating leptin concentrations (Casabiell et al 2001).…”

Section: Discussionmentioning

confidence: 94%

“…In the ob/ob mouse, respiratory anomalies that are common with the obese phenotype (tachypnea, decreased lung compliance and aberrant respiratory muscle adaptations) were attenuated following prolonged leptin administration (Tankersley et al 1998). Similarly, in wild-type mice that were obese merely as a consequence of their high-fat diet, respiratory depression was alleviated by leptin treatment (O'Donnell et al 1999).…”

Section: Introductionmentioning

confidence: 97%

Leptin receptor expression in fetal lung increases in late gestation in the baboon: a model for human pregnancy

Henson

Swan²,

Edwards³

et al. 2004

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Leptin produced by both adipose tissue and the placental trophoblast, has been proposed to regulate numerous aspects of human conceptus development. Although recent animal studies have suggested an additional role for the polypeptide in fetal lung maturation, no evidence has been reported in primates. Therefore, we employed the baboon (Papio sp.), a well-characterized primate model for human pregnancy, to determine the presence and ontogeny of leptin receptor in fetal lung with advancing gestation. Lungs were collected from fetal baboons, early in gestation (days 58-62, n 5 4), at mid gestation (days 98 -102, n 5 4), and late in gestation (days 158 -165, n 5 4) (term 184 days). mRNA transcripts for leptin (LEP) and both long and short intracellular domain isoforms of the leptin receptor (LEP-R L and LEP-R S ) were assessed by RT-PCR. leptin receptor protein was evaluated by immunoblotting and cell types expressing leptin receptor were identified in late pregnancy by immunohistochemistry. Fetal serum leptin concentrations, determined by RIA, remained relatively unchanged at 5.7 6 1.1 ng/ml (mean 6 S.E.M.) in mid pregnancy and 8.4 6 3.0 ng/ml in late pregnancy (P > 0.05). Although leptin were detectable in fetal lung, no changes in transcript abundance were apparent with advancing gestation. However, transcripts for both LEP-R L and LEP-R S receptor isoforms increased several-fold (P < 0.05) in fetal lung between mid and late gestation, while leptin receptor protein was detectable only in late pregnancy. leptin receptor was localized in distal pulmonary epithelial cells, including type II pneumocytes. In conclusion, leptin is present in the fetal baboon and its receptor is enhanced during late gestation in cells responsible for the synthesis of pulmonary surfactant. Collectively, these and past findings may suggest a modulatory role for the polypeptide in pulmonary development and/or may identify leptin receptor as a physiological marker of primate fetal lung maturity.

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“…A central role of leptin as a neurohumoral modulator of central respiratory mechanisms and lung function has furthermore been established in animal models [35].…”

Section: Discussionmentioning

confidence: 99%

Leptin and ghrelin levels in patients with obstructive sleep apnoea: effect of CPAP treatment

Harsch¹,

Konturek²,

Koebnick³

et al. 2003

European Respiratory Journal

252

165

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Serum leptin and ghrelin levels were investigated in patients with obstructive sleep apnoea (OSA) syndrome before and during continuous positive airways pressure (CPAP) treatment and compared with body mass index (BMI)-matched controls without OSA.Male patients (n=30) with OSA (apnoea/hypopnoea index=58 ¡ 16, BMI=32.6 ¡ 5.3 kg?m -2 ) underwent CPAP treatment. Fasting leptin and ghrelin were measured at baseline and 2 days, and in the case of leptin 2 months after initiation of treatment.Baseline plasma ghrelin levels were significantly higher in OSA patients than in controls. After 2 days of CPAP treatment, plasma ghrelin decreased in almost all OSA patients (n=9) to levels that were only slightly higher than those of controls (n=9). Leptin levels did not change significantly from baseline after 2 days of CPAP treatment, but were higher than in the control group. After 8 weeks, leptin levels decreased significantly, although the BMI of the patients showed no change. The decrease in leptin levels was more pronounced in patients with a BMI v30 kg?m -2 . These data indicate that the elevated leptin and ghrelin levels are not determined by obesity alone, since they rapidly decreased during continuous positive airways pressure therapy. Eur Respir J 2003; 22: 251-257 Obstructive sleep apnoea (OSA) is a common disorder affecting 2-4% of the adult population [1]. OSA is strongly associated with obesity. In a recent study involving 773 patients with OSA, only 6.5% had a normal body mass index (BMI), while 75.2% were obese (BMIo30 kg?m -2 ) [2]. Patients with OSA appear to be more likely to put on weight than equally obese subjects without OSA [3]. The mechanisms underlying this phenomenon remain obscure. Recently, a number of authors have speculated that changes in serum leptin levels or leptin-receptor insensitivity may be involved in the pathogenesis of progressive obesity in patients with OSA [4]. Leptin has been found to reduce appetite and simultaneously to increase respiratory drive in an animal model [5,6]. In humans, the situation may be expected to be more complicated. In recent studies, fasting leptin levels in patients with OSA decreased after initiation of continuous positive airways pressure (CPAP) treatment [7,8]. However, those leptin measurements were performed on awake individuals in the morning, when the respiratory situation was normalised, so that any linkage between leptin levels and respiratory effects is difficult in this setting. Furthermore, leptin levels are influenced by a multitude of factors, such as sex, body weight [9,10], the presence of hypertension, or specific medications impacting on leptin levels. Diurnal and ultradian variations in serum leptin levels are further factors complicating profound insights concerning significant respiratory effects [11][12][13].However, the finding that a hormone like leptin is able to cover a variety of biological functions, beyond its well-investigated role for the regulation of body weight and energy expenditure, also prompted the present aut...

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Leptin Prevents Respiratory Depression in Obesity

Cited by 352 publications

References 26 publications

Shared genetic basis for obstructive sleep apnea and adiposity measures

Shared genetic basis for obstructive sleep apnea and adiposity measures

Leptin receptor expression in fetal lung increases in late gestation in the baboon: a model for human pregnancy

Leptin and ghrelin levels in patients with obstructive sleep apnoea: effect of CPAP treatment

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