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1 Division of Clinical and Administrative Pharmacy, College of Pharmacy, and 3 Department of Internal Medicine, College of Medicine, University of Iowa, Iowa City, Iowa 52242; 2 Department of Hypertension and Diabetology, Medical University of Gdansk, Gdansk, Poland; and 4 Division of Hypertension and Division of Cardiovascular Disease, Department of Internal Medicine, Mayo Clinic and Mayo Foundation, Rochester, Minnesota 55905
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ABSTRACT |
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 TOP
 ABSTRACT
 INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
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Patients with obstructive sleep apnea
(OSA) are frequently obese and are predisposed to weight gain. They
also have heightened sympathetic drive. We reasoned that noradrenergic
activation of 
3-receptors on adipocytes would inhibit
leptin production, predisposing to obesity in sleep apnea. We therefore
tested the hypothesis that obesity and predisposition to weight gain in
OSA are associated with low levels of plasma leptin. We prospectively
studied 32 male patients (43 ± 2 yr) with OSA who were newly
diagnosed and never treated and who were free of any other diseases.
Control measurements were obtained from 32 similarly obese closely
matched male subjects (38 ± 2 yr). Leptin levels were 13.7 ± 1.3 and 9.2 ± 1.2 ng/ml in patients with OSA and controls,
respectively (P = 0.02). Weight gain over the year
before diagnosis was 5.2 ± 1.7 and 0.5 ± 0.9 kg in sleep
apnea patients and similarly obese control subjects, respectively
(P = 0.04). Muscle sympathetic activity was 46 ± 4 and 30 ± 4 bursts/min in patients with OSA (n = 16) and control subjects (n = 18), respectively
(P = 0.01). Plasma leptin levels are elevated in newly
diagnosed otherwise healthy patients with untreated sleep apnea beyond
the levels seen in similarly obese control subjects without sleep
apnea. Higher leptin levels in OSA, independent of body fat content, suggest that OSA is associated with resistance to the weight-reducing effects of leptin.
obesity; heart rate; sympathetic nervous system
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INTRODUCTION |
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TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
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LEPTIN, THE PROTEIN PRODUCT of the ob gene, elicits a decrease in appetite with loss of weight (5, 12). Adipocytes are the primary source of leptin (9). Despite the weight-reducing effects of leptin, obese patients have marked increases in leptin levels in proportion to body fat content (2). It is thought that obesity prevails in these subjects because of resistance to the effects of leptin (2).
Obesity is also strongly linked to obstructive sleep apnea (OSA) (19). Patients with sleep apnea have difficulty losing weight and, in fact, are predisposed to excessive weight gain, far more than is evident in similarly obese control subjects proven to be free of OSA (13).
The mechanism predisposing sleep apnea patients to weight gain is
unknown. A recent analysis emphasizes that abnormalities in autonomic
neural circuits should be considered as an important primary cause of
central nervous system-mediated obesity (11). Adrenergic
inhibition of leptin release, with consequent decreases in plasma
leptin levels, may be implicated (10, 11).
Isoproterenol infusions with adrenergic activation of adipocyte
3-receptors results in inhibition of adipocyte leptin
production in humans (14). Treatment of sleep apnea lowers
sympathetic nerve traffic (7, 21) and also
reduces leptin levels (3). We reasoned that the high
sympathetic drive in sleep apnea patients, evidenced by increased
measurements of sympathetic nerve traffic, would act to similarly
suppress adipocyte leptin production in sleep apnea patients. The
consequent lower leptin would help explain obesity and the propensity
to weight gain in patients with sleep apnea. We therefore tested the
hypothesis that leptin levels are lower in patients with sleep apnea
than in similarly obese patients proven to be free of OSA.
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METHODS |
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TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
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Patients. We prospectively studied 64 male subjects (40 ± 11 yr) who had no prior significant medical history and were not taking medications. OSA was evaluated in each subject by complete overnight polysomnographic study. Patients with an apnea-hypopnea index (total number of apneas + hypopneas averaged per hour of sleep) <10 were considered not to have significant sleep-disordered breathing and were classified as control subjects. The study night was the first occasion on which the subjects had undergone a polysomnographic study. Informed written consent was obtained from each subject. The studies were approved by the Institutional Human Use Committee.
Study protocol.
Complete polysomnographic recordings were obtained continuously during
the study, as described previously (16). Hemodynamic and
anthropometric data, weight history, and leptin levels were obtained in
each subject. Blood pressure and heart rate were measured in duplicate
with an automated sphygmomanometer (Dinamap, Critikon, Tampa, FL). Mean
arterial pressure was calculated as the diastolic pressure plus
one-third of the difference between the systolic and diastolic
pressures. Percent body fat was measured by bioelectric impedance
analysis (BIA-101S system, RJL Systems, Mt. Clemens, MI). Sympathetic
nerve activity to muscle (MSNA) was recorded continuously by obtaining
multiunit recordings of postganglionic sympathetic activity to muscle
circulation, measured from a nerve fascicle in the peroneal nerve
posterior to the fibular head, as described previously
(20). MSNA recordings were obtained during 10 min of
undisturbed supine rest while subjects were awake in carefully
standardized conditions. Studies were conducted in the same room and
3 h after the last meal. All subjects were asked to void before the
recordings. None of the subjects had apneas, hyponeas, or oxygen
desaturations during the study. Sympathetic bursts were identified by
careful inspection of the voltage neurogram, and sympathetic activity
was expressed as bursts per minute. Blood was collected from the
antecubital vein of the opposite arm from which blood pressure was
measured. Blood samples were placed on ice until the plasma was
separated at 2,800 rpm for 10 min and stored at 
70°C until the day
of analysis.
Leptin analysis. Plasma leptin levels were measured using an RIA kit from Linco (St. Louis, MO). The assay range was 0.5-100 ng/ml. Inter- and intra-assay coefficients of variation in our laboratory were 7.0 and 5.1%, respectively.
Statistical analysis. Values are means ± SE. Differences in hemodynamics, anthropometric measures, MSNA, and leptin levels between patients with OSA and controls were determined using an unpaired Student's t-test. Analysis of covariance was used to determine differences in leptin between patients with OSA and controls, adjusted for percent body fat. All statistical analyses were completed using SAS (SAS Institute, Cary, NC) and S-Plus (Statistical Sciences, Seattle, WA) computer software programs. Statistical significance was defined as P < 0.05.
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RESULTS |
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TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
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Study subject characteristics are described in Table
1. Patients with OSA
(n = 32) and controls (n = 32) were
matched for age, height, weight, percent body fat, and mean arterial
pressure. Because of difficulties recruiting substantial numbers of
otherwise healthy women with OSA, only male patients and controls were
studied. Leptin levels were 13.7 ± 1.3 and 9.2 ± 1.2 ng/ml
in patients with OSA and controls (P = 0.02),
respectively (Fig. 1). Adjusted for
percent body fat, leptin levels were still higher in patients with OSA
than in controls (P = 0.03). Patients with OSA had a history of weight gain (5.2 ± 1.7 kg) over the year preceding the
study compared with control subjects, in whom average weight increased
by 0.5 ± 0.9 kg (P = 0.04; Fig. 1). Successful
microneurographic studies were completed in 34 subjects. MSNA,
measured in 16 OSA patients, was 46 ± 4 bursts/min compared with
30 ± 4 bursts/min in 18 control subjects (P = 0.01).
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DISCUSSION |
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TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
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The important and novel finding of this study is that plasma leptin levels are elevated in OSA. Circulating plasma leptin levels were ~50% higher in male patients with OSA than in matched controls. The difference in plasma leptin is therefore independent of percent body fat.
The reason for higher leptin levels in sleep apnea is unclear. Our
original expectation was that leptin would be lower in patients with
sleep apnea, secondary to elevated sympathetic nerve activity
stimulating adipocyte -receptors, which would elicit a decrease in
leptin production (14, 16). MSNA was
significantly higher in patients with OSA than in matched controls
(P = 0.01). Despite this potential mechanism for
decreasing leptin production, our data show that sleep apnea is
associated with an increase in leptin levels. One possible explanation
for higher leptin levels may be adipocyte 3-receptor
downregulation as a result of OSA-induced sympathetic activation
(8, 16) or because of other mechanisms (1, 18).
Consistent with an earlier study (13), we confirm that sleep apnea patients are also predisposed to weight gain, even though leptin levels are elevated. High leptin levels should reduce body fat (5, 12). Hyperleptinemia in the presence of obesity per se has been explained by "leptin resistance," namely, inadequate signaling to decrease body fat for a given level of leptin (2). Leptin resistance may therefore predispose patients with sleep apnea to weight gain, even in a milieu of high leptin levels. This may explain the difficulty in weight management in this population, inasmuch as patients with sleep apnea may already be predisposed to weight gain secondary to reduced physical activity resulting from tiredness and daytime somnolence.
Leptin may also affect cardiovascular structure and function. Increases in leptin levels have been linked to elevations in blood pressure, heart rate, and sympathetic nerve activity (4, 6, 15). There is growing evidence that the actions of leptin on the cardiovascular system remain intact, despite the inability of leptin to regulate body fat; central neural control of food intake and sympathetic outflow can be dissociated (11). Thus leptin resistance may be specific to metabolic effects of leptin, with preservation of cardiovascular and/or other effects. Animal studies demonstrate that leptin infusion results in sympathetic activation and tachycardia (4, 6, 15). We have shown that leptin and sympathetic nerve activity are elevated in patients with OSA. Thus higher leptin levels in sleep apnea patients may contribute to the heightened sympathetic drive, even though there is resistance to the weight loss effects of leptin. Indeed, treatment of OSA with continuous positive airway pressure lowers sympathetic traffic (7, 21) and also lowers leptin levels (3). Our data suggest a potential mechanism for the treatment-induced reductions in leptin and sympathetic drive in OSA.
Our findings regarding sleep apnea-specific abnormalities in plasma leptin may have implications for understanding the disordered breathing during sleep in OSA. Tankersley et al. (17) demonstrated impaired ventilatory responses in leptin-deficient ob/ob mice. Leptin resistance with respect to ventilatory control may be involved in abnormalities in breathing control mechanisms in patients with OSA.
The strengths of this study include closely matched demographics of the sleep apnea patients and similarly obese subjects who were proven to be free of sleep-disordered breathing. Neither patients nor controls were on medications, nor did they have any significant medical history. Our study is limited, in that our data were obtained only from men. Our findings cannot be extrapolated to female patients with sleep apnea. Furthermore, our measurements of plasma leptin may not directly reflect levels of leptin in cerebrospinal fluid.
In conclusion, we have demonstrated, first, that circulating plasma leptin levels are elevated in newly diagnosed male patients with untreated sleep apnea and, second, that there is a propensity to weight gain in sleep apnea patients, even in the setting of higher leptin levels. High leptin levels in obesity per se likely reflect resistance to metabolic effects of leptin. OSA may be accompanied by further resistance to metabolic effects of leptin, greater than the resistance evident in obesity alone.
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ACKNOWLEDGEMENTS |
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V. K. Somers and B. G. Phillips are Sleep Academic Awardees of the National Institutes of Health. V. K. Somers is an Established Investigator of the American Heart Association. These studies were also supported by National Heart, Lung, and Blood Institute Grants HL-61560, HL-65176, and HL-14388 (to B. G. Phillips and V. K. Somers).
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FOOTNOTES |
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Address for reprint requests and other correspondence: V. K. Somers, Div. of Hypertension and Div. of Cardiovascular Diseases, Dept. of Internal Medicine, Mayo Clinic, 200 First St. SW, Rochester, MN 55905 (E-mail: somers.virend{at}mayo.edu).
The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. §1734 solely to indicate this fact.
Received 15 November 1999; accepted in final form 10 January 2000.
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REFERENCES |
|---|
|
TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
|
|---|
1.
Berkowitz, DE,
Brown D,
Lee KM,
Emala C,
Palmer D,
An Y,
and
Breslow M.
Endotoxin-induced alteration in the expression of leptin and 3-adrenergic receptor in adipose tissue.
Am J Physiol Endocrinol Metab
274:
E992-E997,
1998
2.
Caro, JF,
Sinha MK,
Kolaczynski JW,
Zhang PL,
and
Considine RV.
Leptin: the tale of an obesity gene.
Diabetes
45:
1455-1462,
1996[ISI][Medline].
3.
Chin, K,
Shimizu K,
Nakamura T,
Narai N,
Masuzaki H,
Ogawa Y,
Mishima M,
Nakamura T,
Nakao K,
and
Ohi M.
Changes in intra-abdominal visceral fat and serum leptin levels in patients with obstructive sleep apnea syndrome following nasal continuous positive airway pressure therapy.
Circulation
100:
706-712,
1999
4.
Gettys, TW,
Harkness PJ,
and
Watson PM.
The 3-adrenergic receptor inhibits insulin-stimulated leptin secretion from isolated rat adipocytes.
Endocrinology
137:
4054-4057,
1996[Abstract].
5.
Halaas, JL,
Gajiwala KS,
Maffei M,
Cohen SL,
Chait BT,
Rabinowitz D,
Lallone RL,
Burley SK,
and
Friedman JM.
Weight-reducing effects of the plasma protein encoded by the obese gene.
Science
269:
543-546,
1995
6.
Haynes, WG,
Morgan DA,
Walsh SA,
Mark AL,
and
Sivitz WI.
Receptor-mediated regional sympathetic nerve activation by leptin.
J Clin Invest
100:
270-278,
1997[ISI][Medline].
7.
Hedner, J,
Darpo B,
Ejnell H,
Carlson J,
and
Caidahl K.
Reduction in sympathetic activity after long-term CPAP treatment in sleep apnoea: cardiovascular implications.
Eur Respir J
8:
222-229,
1995[Abstract].
8.
Klaus, S,
Muzzin P,
Revelli JP,
Cawthorne MA,
Giacobino JP,
and
Ricquier D.
Control of 3-adrenergic receptor gene expression in brown adipocytes in culture.
Mol Cell Endocrinol
109:
189-195,
1995[ISI][Medline].
9.
Lonnquist, F,
Arner P,
Nordford L,
and
Schalling M.
Overexpression of the obese (ob) gene in adipose tissue of human obese subjects.
Nat Med
1:
950-953,
1995[ISI][Medline].
10.
Mantzoros, CS,
Qu D,
Frederich RC,
Susulic VS,
Lowell BB,
Maratos-Flier E,
and
Flier JS.
Activation of 3-adrenergic receptors suppresses leptin expression and mediates a leptin-independent inhibition of food intake in mice.
Diabetes
45:
909-914,
1996[Abstract].
11.
Nonogaki, K.
Obesity: autonomic circuits versus feeding.
Nat Med
5:
742-743,
1999[ISI][Medline].
12.
Pelleymounter, MA,
Cullen MJ,
Baker MB,
Hecht R,
Winters D,
Boone T,
and
Collins F.
Effects of the obese gene product on body weight regulation in ob/ob mice.
Science
269:
540-543,
1995
13.
Phillips, BG,
Hisel TM,
Kato M,
Pesek CA,
Dyken ME,
Narkiewicz K,
and
Somers VK.
Recent weight gain in patients with newly diagnosed obstructive sleep apnea.
J Hypertens
17:
1297-1300,
1999[ISI][Medline].
14.
Pinkney, JH,
Coppack SW,
and
Mohamed-Ali V.
Effect of isoprenaline on plasma leptin and lipolysis in humans.
Clin Endocrinol (Oxf)
48:
407-411,
1998[Medline].
15.
Shek, EW,
Brands MW,
and
Hall JE.
Chronic leptin infusions increase arterial pressure.
Hypertension
31:
409-414,
1998
16.
Somers, VK,
Dyken ME,
Clary MP,
and
Abboud FM.
Sympathetic neural mechanisms in obstructive sleep apnea.
J Clin Invest
96:
1897-1904,
1995.
17.
Tankersley, C,
Kleeberger S,
Russ B,
Schwartz A,
and
Smith P.
Modified control of breathing in genetically obese (ob/ob) mice.
J Appl Physiol
81:
716-723,
1996
18.
Vgontzas, AN,
Papanicolaou DA,
Bixler EO,
Kales A,
Tyson K,
and
Chrousos GP.
Elevation of plasma cytokines in disorders of excessive daytime sleepiness: role of sleep disturbance and obesity.
J Clin Endocrinol Metab
82:
1313-1316,
1997
19.
Vgontzas, AN,
Tan TL,
Bixler EO,
Martin LF,
Shubert D,
and
Kales A.
Sleep apnea and sleep disruption in obese patients.
Arch Intern Med
154:
1705-1711,
1994[Abstract].
20.
Wallin, G.
Intraneural recordings and autonomic function in man.
In: Autonomic Failure, edited by Banister R.. London: Oxford University Press, 1983, p. 36-51.
21.
Waradekar, NV,
Sinoway LI,
Zwillich CW,
and
Leuenberger UA.
Influence of treatment on muscle sympathetic nerve activity in sleep apnea.
Am J Respir Crit Care Med
153:
1333-1338,
1996[Abstract].
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T. L. Clanton, V. P. Wright, P. J. Reiser, P. F. Klawitter, and N. R. Prabhakar Physiological and Genomic Consequences of Intermittent Hypoxia: Selected Contribution: Improved anoxic tolerance in rat diaphragm following intermittent hypoxia J Appl Physiol, June 1, 2001; 90(6): 2508 - 2513. [Abstract] [Full Text] [PDF]
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