LEPTIN LEVELS OF ALCOHOL ABSTAINERS AND DETOXIFICATION PATIENTS ARE NOT DIFFERENT

Friedrich Martin Wurst*, Gaby Bechtel1, Stefan Forster1, Manfred Wolfersdorf1, Peter Huber2, André Scholer2, Lutz Pridzun3, Andreas Alt4, Stephan Seidl5, Jutta Dierkes6 and Gerhard Dammann

Psychiatric University Clinic and
2 Department Central Laboratory, University of Basel, Switzerland,
1 State Mental Hospital Bayreuth,
3 Mediagnost Inc., Reutlingen, Departments of Legal Medicine, Universities of
4 Ulm and
5 Erlangen and
6 Department of Clinical Chemistry, University of Magdeburg, Germany

Received 2 January 2003; in revised form 25 February 2003; in revised form 19 March 2003; accepted 24 March 2003


    ABSTRACT
 TOP
 FOOTNOTES
 ABSTRACT
 INTRODUCTION
 SUBJECTS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
Aims: Leptin is a cytokine-type peptide hormone, recently implicated as a putative state marker of alcohol use and in craving. Our goal was to evaluate the potential of leptin as a state and trait marker and to rule out the role of current alcohol intoxication on leptin levels. Methods: Eighteen alcohol withdrawal patients (16 males, 2 females) whose blood contained 202 mg/dl (median) of ethanol at hospitalization, who had a median age of 43.5 years and had consumed 1075 g of ethanol (median) in the last 7 days were included in the study. Leptin was determined in samples at day 1 (when still intoxicated) and day 7 of withdrawal. Expected leptin levels were calculated with a formula. For comparison, 27 blood samples of 18 abstinent persons, matched for gender, age and body mass index were used. Furthermore, mean cell volume, {gamma}-glutamyl transferase (GGT), blood glucose, cholesterol, triglycerides and body composition (bioimpedance device) were determined. For statistical analysis, SPSS 11 was used. Results: Expected leptin levels were 1.71 ng/ml (median), leptin measured at day 1 was 2.65 ng/ml (median) and 2.85 ng/ml on day 7 for the alcohol withdrawal patients and 2.2 ng/ml (median) for the abstainers. These concentrations were not significantly different. Significant correlations were found between leptin day 1 and expected leptin levels, percentage fat body mass, cigarettes smoked per day, GGT and blood alcohol concentration. Conclusions: Our preliminary data do not support the hypothesis of leptin as a state or trait marker and suggest only a minor influence of acute intoxication on leptin levels in alcohol detoxification patients.


    INTRODUCTION
 TOP
 FOOTNOTES
 ABSTRACT
 INTRODUCTION
 SUBJECTS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
There is an increasing body of evidence that cytokines, including leptin, play a key role in alcoholism. Leptin is a cytokine-type peptide hormone, mainly synthesized in adipocytes, but also in placenta, gastric fundic mucosa and skeletal muscle. It is distributed widely in various tissues and is cleared mainly by the kidney. Systemic effects include effects on energy homeostasis, regulation of neuroendocrine and immune function and in development (Ahima and Flier, 2000Go). It circulates, partly bound to plasma proteins, as a 16-kDa protein. Leptin levels in blood correlate with total body fat mass; however, it is not known whether increased triglyceride levels, lipid metabolites or mechanical factors associated with increased adipocyte size influence leptin expression (Ahima and Flier, 2000Go). Leptin receptors and insulin receptors are expressed by brain neurons involved in energy expenditure (Schwartz et al., 2000Go). The signalling pathways that mediate the metabolic effects of leptin remain undefined (Minokoshi et al., 2002Go). There is some evidence that leptin and soluble tumour necrosis factor receptor (sTNF-R) or other parameters could be predictors for gaining weight and unfavourable changes of body composition (Herran et al., 2001Go; Melkersson and Hulting, 2001).

Rasmussen et al.(2002)Go have investigated the effects of chronic daily ethanol consumption, withdrawal and subsequent abstinence on adult rat forebrain opiomelanocortinergic activity. Plasma concentrations of corticosterone, testosterone and leptin were also altered by the daily ethanol/withdrawal treatment (consumption at night and withdrawal during the day) and by subsequent abstinence. Obradovic and Meadows (2002)Go found that chronic ethanol consumption in mice increases the circulating level of leptin and that this is accompanied by altered expression of leptin-sensing molecules in the hypothalamus and peripheral adipose tissue. These results suggest that chronic ethanol intake (in mice) affects metabolism by altering the leptin system that regulates energy balance. There was also evidence from epidemiological studies that, among other lifestyle variables, alcohol consumption influences serum leptin levels (Wei et al., 1997Go; Mantzoros et al., 1998Go; Langiou et al., 1999). A decreased leptin renal excretion with increased leptin levels has been documented in alcoholic patients with advanced liver disease (Henriksen et al., 1999Go). Song et al.(1999)Go reported significantly higher production of interleukin 6 (IL-6), IL-10 and tumour necrosis factor-{alpha} (TNF{alpha}) in detoxified alcoholic patients without liver disease compared with healthy volunteers.

Recently the issue of leptin as a putative state marker of alcohol use has been raised by Nicolas et al.(2001)Go. In a multivariate regression analysis they found that the fat area of the arm, the lifetime ethanol consumption and the number of cigarettes smoked per day were independent factors influencing leptin in alcohol-dependent patients regardless of nutritional status or the presence of a compensated liver disease. Circulating leptin levels were increased in a dose-dependent manner in active chronic alcoholism (Nicolas et al., 2001Go). In contrast, Santolaria et al. (2003)Go reported decreased leptin levels in alcoholic patients even after adjusting for the amount of body fat. Togo et al.(2000)Go observed no association between the level of leptin and smoking or alcohol consumption in 708 Japanese men, although other studies (Wei et al., 1997Go; Mantzoros et al., 1998Go; Donahue et al., 1999Go; Nicklas et al., 1999Go; Chu et al., 2001Go) reported a marked inverse effect of smoking on serum levels of leptin, offering a possible explanation for variation in body weight between smokers and non-smokers. Mantzoros et al.(1998)Go found that circulating leptin concentrations independently and positively associated with alcohol intake, whereas other studies reported no (De Silva et al., 1998Go; Lagiou et al., 1999Go; Togo et al., 2000Go) or opposite relationships (Donahue et al., 1999Go).

Röjdmark et al.(2001)Go have shown that acute ethanol intake by healthy individuals is followed by decreased serum leptin levels. They speculate that alcohol might serve as an appetizer by decreasing leptin secretion, but additional studies are necessary to prove this hypothesis since previous studies have shown that leptin has a long-term rather than an acute effect on hunger. The data of the study of Hiney et al.(1999)Go demonstrated that ethanol administration not only suppresses peripheral levels of leptin but also blocks its central action to facilitate luteinizing hormone secretion. The findings of Fujita et al.(2003)Go suggest that ethanol-induced enhancement of appetite may, in part, result from leptin resistance transiently caused by ethanol to attenuate the leptin signal transduction. Surprisingly, leptin was significantly elevated in the offspring of paternally ethanol-exposed rats (after 2 months of ethanol feeding) (Emanuele et al., 2001Go).

Kiefer et al. (2001aGo,bGo,cGo) tested the hypothesis that the application of exogenous leptin modulates voluntary alcohol consumption in mice. They found significantly elevated free-choice ethanol consumption after withdrawal in mice following intraperitoneal injection of 1 mg/kg leptin, but not during basal drinking (Kiefer et al., 2001cGo). Therefore they suggest that leptin may enhance motivation for alcohol consumption in habituated mice after alcohol withdrawal. In another study on 20 alcohol-dependent patients, they raised the question of leptin as a possible modulator for craving (Kiefer et al., 2001bGo). Leptin levels were found to be elevated in alcohol-dependent patients and correlated with craving as assessed by a visual analogue scale. In a recent study on 30 male alcoholic patients, Kiefer et al.(2002)Go measured leptin and TNF{alpha} levels and craving the day following admission to hospital. The increased leptin levels correlated with craving.

The aim of the present study was to evaluate the potential of leptin as a state and trait marker and to rule out the role of current alcohol intoxication in the control of leptin levels.


    SUBJECTS AND METHODS
 TOP
 FOOTNOTES
 ABSTRACT
 INTRODUCTION
 SUBJECTS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
Patients
Eighteen alcohol withdrawal patients (16 males, 2 females), aged 43.25 years (median), who had consumed 1075 g of ethanol (median) in the last 7 days were included. All were intoxicated with 202 mg/dl (median) of alcohol in their blood at hospitalization. The diagnosis of alcoholism was established according to ICD 10 criteria (alcohol use dependence syndrome; continuous use, F 10.25) (World Health Organization, 1992). Descriptive statistics are given in Table 1Go. A screening for illicit drug use was negative in all cases. Other exclusion criteria were admission to hospital after 14:00 h, severe somatic illnesses, especially liver cirrhosis and diseases of the kidney, and no current alcohol intoxication. All subjects gave written informed consent prior to the investigation.


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Table 1. Descriptive statistics of different parameters determined
 
Blood samples were taken between 07:00 and 14:00 h, both for day 1 and day 7. Withdrawal symptoms were assessed by a procedure based on heart rate, blood pressure, tremor, agitation and anxiety among other factors. On this basis, clomethiazole was prescribed at a maximum of 2 capsules (192 mg per capsule)/2 h, 20 capsules/24 h.

For comparison 27 blood samples of 18 abstinent addicted persons, matched for age (Mann–Whitney test: P = 0.118), gender (16 males, 2 females) and body mass index (BMI) (P = 0.143) were used.

Methods
Leptin was determined in samples on day 1 (immediately after hospitalization, when patients were still intoxicated with alcohol) and day 7 of withdrawal with a Human Leptin Standard RIA Kit (Mediagnost Inc., Reutlingen, Germany). Expected leptin levels were calculated with the formula:

for adult men a = 0.0130, b = 0.22; for adult women a = 0.3042 and b = 0.1467 (http://www.mediagnost.de/02deu/02.htm, January 2, 2003). In addition, routine parameters, including {gamma}-glutamyl transferase (GGT), mean cell volume (MCV) and blood glucose were determined.

Body composition was measured using a bioimpedance device (Tanita Europe, Sindelfingen, Germany). Body surface was calculated according to the formula of Du Bois and Du Bois, 1916Go:

Statistical analysis
For statistical analysis, SPSS 11 (SPSS Inc., Chicago, IL, USA) was used. Categorical variables not fitting the normal distribution were compared using non-parametric tests: the Kruskal–Wallis for multiple variables and the Mann–Whitney U-test. Correlations presented are Spearman rank correlations.


    RESULTS
 TOP
 FOOTNOTES
 ABSTRACT
 INTRODUCTION
 SUBJECTS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
Leptin on day 1 was 2.65 ng/ml (median), 2.85 ng/ml (median) on day 7 for the detoxification patients and 2.2 ng/ml (median) for the abstainers (Fig. 1Go).



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Fig. 1. Boxplots for leptin levels (ng/ml) of the controls, the patients during detoxification (day 1, day 7) and expected leptin levels. Shown are each median, 25th and 75th quartile of the leptin levels of the four groups. There were no significant differences between the groups (Kruskal–Wallis: P = 0.366).

 
There were no significant differences in leptin levels in Mann–Whitney test between those who were hospitalized between 07:00 and 10:00 h (n = 9), and those who were hospitalized between 10:00 and 14:00 h (n = 11) (P = 0.297) on day 1. The findings for day 7 were analogous (P = 0.364). Leptin levels on day 1 and day 7 and expected leptin levels were not significantly different (P = 0.256, Kruskal–Wallis).

Significant correlation (Spearman rank correlation) was found between leptin and expected leptin levels, percentage fat body mass, BMI, GGT, blood alcohol concentration (BAC) and cigarettes smoked per day (Table 2Go). However, when using the ratio of leptin day 1/percentage body fat, no significant correlation was found with GGT, BAC and number of cigarettes.


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Table 2. Correlation between leptin days 1 and 7, expected leptin levels and other parameters
 
The median for years since first diagnosis of alcoholism was 16, number of in-patient detoxifications was 4, age of onset of alcoholism was 21 and age of first in-patient detoxification was 36. The Mann–Whitney test was performed using the median cut. For the above-mentioned group variables and leptin (day 1 and day 7) as test variables no group significance was found.


    DISCUSSION
 TOP
 FOOTNOTES
 ABSTRACT
 INTRODUCTION
 SUBJECTS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
As the main result we found no significant difference in leptin levels of detoxification patients on day 1, day 7, calculated leptin level and leptin levels of abstainers. Consequently, there was a good correlation between these parameters and the leptin levels as expected from the calculation. As leptin levels in the alcohol detoxification patients, expected leptin levels and levels in abstainers are not statistically different, the hypothesis of leptin as a trait marker finds no support in this study. Furthermore, the data do not suggest leptin as a state marker, as expected levels and levels on days 1 and 7 as well as levels of abstainers were not significantly different. These results are in contrast to some other studies (Kiefer et al., 2001aGo; Nicolas et al., 2001Go; Santolaria et al., 2003Go). Three major points in the presented study may contribute to the divergent results: (1) the determination of percentage body fat with a fairly precise device, giving more accurate information than BMI or skin-fold measurement; (2) all patients were initially intoxicated with alcohol; and (3) to our knowledge it was the first time in this context that individually calculated standard values were used. The determination of fat body mass is of significance as leptin is a hormone derived from the adipose tissue. Numerous methods and devices are used to measure body fat, including bioimpedance as in our study. A possible limitation of our study could be an overestimation of percentage body fat for a gynoid type of fat distribution with the Tanita device used.

Furthermore we found, in contrast to others, no significantly elevated (Kiefer et al. 2001aGo,bGo; Nicolas et al. 2001Go) or decreased (Santolaria et al., 2003Go) leptin levels at the beginning of the detoxification. However, we compared days 1 and 7, whereas others (Kiefer et al., 2001aGo,bGo; Santolaria et al., 2003Go) compared days 1 and 14. On the other hand, we found no difference between the measured levels of detoxification patients and abstainers, or compared with expected levels. Santolaria et al.(2003)Go reported decreased circulating serum leptin levels in chronic alcoholic patients without acute intoxication. This decrease was considered by the authors to be a consequence of a low fat mass. Although the data presented to date are inconsistent even as to whether leptin levels are elevated, normal or decreased in chronic alcoholism, it seems promising to consider the possibility of interactions between chronic and acute effects that could, based on the current state of knowledge, be synergistic, neutral or antagonistic. Clearly, the limitation of our study is that we cannot differentiate these possible effects at admission to hospital. However, we should like to point out that no significant differences were found between day 1 and day 7 in alcoholic patients, the abstainers and the expected level, which could possibly indicate that a potential influence is rather limited or antagonistic effects are seen at admission with acute intoxication being superimposed on a longer lasting intake of alcohol. The negative correlation with nicotine, as previously reported in other studies (Mantzoros et al., 1998Go; Donahue et al., 1999Go; Chu et al., 2001Go), might be explained partly by the following: those smoking the most have the lowest percentage of body fat and thus the lowest leptin levels. Santolaria et al.(2003)Go, too, found that smokers had a lower fat mass that non-smokers and leptin depends mainly on fat mass, but not on smoking habit itself.

An aspect to be further examined is the fact that alcohol withdrawal can be understood as acute stress. Alcohol-dependent patients have an impaired cortisol response to stress, indicating dysregulation in the extrahypothalamic systems responsible for activating cortisol secretion in response to stressor exposure (Errico et al., 2002Go). The endocrine effects of stress for alcoholic patients during the withdrawal phase have been demonstrated. Another important question concerns the association of plasma leptin level with cortisol, which is known as a metabolic regulator of various stress-related factors, during alcohol withdrawal. No significant relationship between plasma cortisol and leptin, BMI or the leptin/BMI ratio was detected in either the alcoholic or control subject groups in the study of Kiefer et al. (2001a)Go. There is no striking evidence that the phase of alcohol withdrawal, treated with clomethiazole, produces measurable endocrinological stress (Rasmussen et al., 2000Go). Also, it is known that stress-related hormones in alcoholic patients are altered for longer periods, even weeks after withdrawal (Baumgartner et al., 1994Go; Ehrenreich et al., 1997Go). However, even if alcohol withdrawal treated by clomethiazole increased cortisol, a possible relationship between the neurobiology of these two systems (cortisol and leptin) is contradictory (Kain et al., 1999Go; Wallace et al., 2000Go; Modan-Moses et al., 2001Go; Schafroth et al., 2001Go).

There are results indicating that glucocorticoids enhance the amplitude of leptin diurnal rhythm, which is consistent with previous findings showing that glucocorticoids increase leptin secretion (Nishiyama et al., 2000Go). Corticotropin releasing hormone hyperactivity persists after 12 weeks of alcohol withdrawal in alcoholic patients, especially with co-morbid disorders (Ehrenreich et al., 1997Go). To assess the action of this hormone on brain reward circuitry, changes in the rewarding effect of lateral hypothalamic stimulation were measured after leptin administration by Fulton et al.(2000)Go. Kiefer et al. (2001cGo, 2002Go) have explained the association of increased alcohol craving with higher plasma leptin in their alcoholic sample with the reward theory of Fulton et al.(2000)Go. Other neurobiological factors, like GABAergic mechanisms, might also contribute to the complex mechanisms regulating leptin levels.

From a theoretical viewpoint, as well as from preclinical and clinical results, the idea of an influence of leptin on alcohol consumption, or of alcohol on leptin levels, mediated by inflammatory processes including TNF{alpha} is striking. Further studies under well-defined conditions are needed to address these points.


    FOOTNOTES
 TOP
 FOOTNOTES
 ABSTRACT
 INTRODUCTION
 SUBJECTS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
* Author to whom correspondence should be addressed at: Psychiatric University Clinic, University of Basel, Wilhelm Klein-Strasse 27, CH-4025 Basel, Switzerland. Back


    REFERENCES
 TOP
 FOOTNOTES
 ABSTRACT
 INTRODUCTION
 SUBJECTS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
Ahima, R. S. and Flier, J. S. (2000) Leptin. Annual Review of Physiology 62, 413–437.[CrossRef][ISI][Medline]

Baumgartner, A., Rommelspacher, H., Otto, M., Schmidt, L. G., Kurten, I., Graf, K. J., Campos-Barros, A. and Platz, W. (1994) Hypothalamic–pituitary–thyroid (HPT) axis in chronic alcoholism. I. HPT axis in chronic alcoholics during withdrawal and after 3 weeks of abstinence. Alcoholism: Clinical and Experimental Research 18, 284–294.[ISI][Medline]

Chu, N. F., Stampfer, M. J., Spiegelman, D., Rifai, N., Hotamisligil, G. S. and Rimm, E. B. (2001) Dietary and lifestyle factors in relation to plasma leptin concentrations among normal weight and overweight men. International Journal of Obesity and Related Metabolic Disorders 25, 106–114.[CrossRef][Medline]

De Silva, A., De Courten, M., Zimmet, P., Nicholson, G., Kotowicz, M., Pasco, J. and Collier, G. R. (1998) Lifestyle factors fail to explain the variation in plasma leptin concentrations in women. Nutrition 14, 653–657.[CrossRef][ISI][Medline]

Donahue, R. P., Zimmet, P., Bean, J. A., Decourten, M., Donahue, R. A., Collier, G., Goldberg, R. B., Prineas, R. J., Skyler, J. and Schneiderman, N. (1999) Cigarette smoking, alcohol use, and physical activity in relation to serum leptin levels in a multiethnic population: The Miami Community Health Study. Annals of Epidemiology 9, 108–113.[CrossRef][ISI][Medline]

Du Bois, D. and Du Bois, E. F. (1916) A formula to estimate the approximate surface area if height and weight are known. Archives of Internal Medicine 17, 863.

Ehrenreich, H., Schuck, J., Stender, N., Pilz, J., Gefeller, O., Schilling, L., Poser, W. and Kaw, S. (1997) Endocrine and hemodynamic effects of stress versus systemic CRF in alcoholics during early and medium term abstinence. Alcoholism: Clinical and Experimental Research 21, 1285–1293.[ISI][Medline]

Emanuele, N. V., LaPagli, N., Steiner, J., Colantoni, A., Van Thiel, D. H. and Emanuele, M. A. (2001) Peripubertal paternal EtOH exposure. Endocrine 14, 213–219.[CrossRef][ISI][Medline]

Errico, A. L., King, A. C., Lovallo, W. R. and Parsons, O. A. (2002) Cortisol dysregulation and cognitive impairment in abstinent male alcoholics. Alcoholism: Clinical and Experimental Research 26, 1198–1204.[ISI][Medline]

Fujita, N., Sakamaki, H., Uotani, S., Takahashi, R., Kuwahara, H., Kita, A., Oshima, K., Yamasaki, H., Yamaguchi, Y. and Eguchi, K. (2003) Acute effects of ethanol on feeding behavior and leptin-induced STAT3 phosphorylation in rat hypothalamus. International Journal of Obesity and Related Metabolic Disorders 27, 55–59.[CrossRef][Medline]

Fulton, S., Woodside, B. and Shizgal, P. (2000) Modulation of brain reward circuitry by leptin. Science 287, 125–128.[Abstract/Free Full Text]

Henriksen, J. H., Holst, J. J., Moller, S., Brinch, K. and Bendtsen, F. (1999) Increased circulating leptin in alcoholic cirrhosis: Relation to release and disposal. Hepatology 29, 1818–1824.[ISI][Medline]

Herran, A., Garcia-Unzueta, M. T., Amado, J. A., de La Maza, M. T., Alvarez, C. and Vazquez-Barquero, J. L. (2001) Effects of long-term treatment with antipsychotics on serum leptin levels. British Journal of Psychiatry 179, 59–62.[Abstract/Free Full Text]

Hiney, J. K., Dearth, R. K., Lara, F., Wood, S., Srivastva, V. and Les Dees, W. (1999) Effects of ethanol on leptin secretion and the leptin-induced luteinizing hormone (LH) release from late juvenile female rats. Alcoholism: Clinical and Experimental Research 23, 1785–1792.[ISI][Medline]

Kain, Z. N., Zimolo, Z. and Heninger, G. (1999) Leptin and the perioperative neuroendocrinological stress response. Journal of Clinical Endocrinology and Metabolism 84, 2438–2442.[Abstract/Free Full Text]

Kiefer, F., Jahn, H., Jaschinski, M., Holzbach, R., Wolf, K., Naber, D. and Wiedemann, K. (2001a) Leptin: A modulator of alcohol craving? Biological Psychiatry 49, 782–787.[CrossRef][ISI][Medline]

Kiefer, F., Jahn, H., Kellner, M., Naber, D. and Wiedemann, K. (2001b) Leptin as possible modulator of craving for alcohol. Archives of General Psychiatry 58, 509–510.[Free Full Text]

Kiefer, F., Jahn, H., Wolf, K., Kämpf, P., Knaudt, K. and Wiedemann, K. (2001c) Free choice alcohol consumption in mice after application of the appetite regulating peptide leptin. Alcoholism: Clinical and Experimental Research 25, 787–789.[CrossRef][ISI][Medline]

Kiefer, F., Jahn, H., Schick, M. and Wiedemann, K. (2002) Alcohol intake, tumour necrosis factor alpha, leptin and craving: Factors of a possibly vicious circle? Alcohol and Alcoholism 37, 401–404.[Abstract/Free Full Text]

Lagiou, P., Signorello, L. B., Mantzoros, C. S., Trichopoulos, D., Hsieh, C. C. and Trichopoulou, A. (1999) Hormonal, lifestyle, and dietary factors in relation to leptin among elderly men. Annals of Nutrition and Metabolism 43, 23–29.[CrossRef][ISI][Medline]

Mantzoros, C. S., Liolios, A. D., Tritos, N. A., Kaklamani, V. G., Doulgerakis, D. E., Griveas, I., Moses, A. C. and Flier, J. S. (1998) Circulating insulin concentrations, smoking, and alcohol intake are important independent predictors of leptin in young healthy men. Obesity Research 6, 179–186.[Abstract]

Melkersson, K. I. and Hultin, A. L. (2001) Insulin and leptin levels in patients with schizophrenia or related psychoses — a comparison between different antipsychotic agents. Psychopharmacology 154, 205–212.[CrossRef][ISI][Medline]

Minokoshi, Y., Kim, Y.-B., Peronie, O. D., Fryer, L. G. D., Müller, C., Carling, D. and Kahn, B. B. (2002) Leptin stimulates fatty acid oxidation by activating AMP-activated protein kinase. Nature 415, 339–343.[CrossRef][ISI][Medline]

Modan-Moses, D., Ehrlich, S., Kanety, H., Dagan, O., Pariente, C., Esrahi, N., Lotan, D., Vishne, T., Barzilay, Z. and Paret, G. (2001) Circulating leptin and the perioperative neuroendocrinological stress response after pediatric cardiac surgery. Critical Care Medicine 12, 2377–2382.[CrossRef]

Nicklas, B. J., Tomayasu, N., Muir, J. and Goldberg, A. P. (1999) Effects of cigarette smoking and its cessation on body weight and plasma leptin levels. Metabolism 48, 804–808.[ISI][Medline]

Nicolas, J. M., Fernandez-Sola, J., Fatjo, F., Casamitjana, R., Bataller, R., Sacanella, E., Tobias, E., Badia, E. and Estruch, R. (2001) Increased circulating leptin levels in chronic alcoholism. Alcoholism: Clinical and Experimental Research 25, 83–88.[CrossRef][ISI][Medline]

Nishiyama, M., Makino, S., Suemaru, S., Nanamiya, W., Asaba, K., Kaneda, T., Mimoto, T., Nishioka, T., Takao, T. and Hashimoto, K. (2000) Glucocorticoid effects on the diurnal rhythm of circulating leptin levels. Hormone Research 54, 69–73.[CrossRef][ISI][Medline]

Obradovic, T. and Meadows, G. G. (2002) Chronic ethanol consumption increases plasma leptin levels and alters leptin receptors in the hypothalamus and the perigonadal fat of C57BL/6 mice. Alcoholism: Clinical and Experimental Research 26, 255–262.[ISI][Medline]

Rasmussen, D. D., Boldt, B. M., Bryant, C. A., Mitton, D. R., Larsen, S. A. and Wilkinson, C. W. (2000) Chronic daily ethanol and withdrawal: 1. Long-term changes in the hypothalamo-pituitary-adrenal axis. Alcoholism: Clinical and Experimental Research 24, 1836–1849.[CrossRef][ISI][Medline]

Rasmussen, D. D., Boldt, B. M., Wilkinson, C. W. and Mitton, D. R. (2002) Chronic daily ethanol and withdrawal: Forebrain pro-opiomelanocortin gene expression and implications for dependence, relapse and deprivation effect. Alcoholism: Clinical and Experimental Research 26, 535–546.[CrossRef][ISI][Medline]

Röjdmark, S., Calissendorff, J. and Brismar, K. (2001) Alcohol ingestion decreases both diurnal and nocturnal secretion of leptin in healthy individuals. Clinical Endocrinology 55, 639–647.[CrossRef][ISI][Medline]

Santolaria, F., Pérez-Cejas, A., Alemán, M.-R., Gonzáles-Reimers, E., Milena, A., de la Vega, M.-J., Martínez-Riera, A. and Gómez-Rodríguez, M.-A. (2003) Low serum leptin levels and malnutrition in chronic alcohol misusers hospitalized by somatic complications. Alcohol and Alcoholism 38, 60–66.[Abstract/Free Full Text]

Schafroth, U., Godang, K., Ueland, T. and Bollerslev, J. (2001) Leptin response to endogenous acute stress is independent of pituitary function. European Journal of Endocrinology 145, 295–301.[ISI][Medline]

Schwartz, M. W., Woods, S. C., Porte, D., Jr, Seely, R. J. and Baskin, D. G. (2000) Central nervous system control of food intake. Nature 404, 661–671.[ISI][Medline]

Song, C., Lin, A., De Jong, R., Vandoolaeghe, E., Kenis, G., Bosmans, E., Whelan, A., Scharpe, S. and Maes, M. (1999) Cytokines in detoxified patients with chronic alcoholism without liver disease: Increased monocytic cytokine production. Biological Psychiatry 45, 1212–1216.[CrossRef][ISI][Medline]

Togo, M., Hashimoto, Y., Futamura, A., Tsukamoto, K., Satoh, H., Hara, M., Watanabe, T., Nakarai, H., Nakahara, K. and Kimura, S. (2000) Relationship between the serum level of leptin and life style habits in Japanese men. Hormone Research 54, 169–173.[CrossRef][ISI][Medline]

Wallace, A. M., Sattar, N. and McMillan, D. C. (2000) The co-ordinated cytokine/hormone response to acute injury incorporates leptin. Cytokine 12, 1042–1045.[CrossRef][ISI][Medline]

Wei, M., Stern, M. P. and Haffner, S. M. (1997) Serum leptin levels in Mexican Americans and non-Hispanic whites: Association with body mass index and cigarette smoking. Annals of Epidemiology 7, 81–86.[CrossRef][ISI][Medline]





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