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1.
Drug Alcohol Depend ; 99(1-3): 333-7, 2009 Jan 01.
Article in English | MEDLINE | ID: mdl-18818026

ABSTRACT

Recent studies suggested a role of appetite regulating peptides like leptin and ghrelin in alcohol dependence and particularly in the neurobiology of alcohol craving. Aim of the present study was to investigate alterations of the adipocytokines adiponectin and resistin in alcohol-dependent patients. We analyzed a sample of 88 patients at admission for alcohol detoxification and after 1 week of withdrawal treatment in comparison to 89 healthy controls. Adiponectin and resistin serum levels were measured using commercial ELISA kits. The extent of alcohol craving was obtained using the Obsessive Compulsive Drinking Scale (OCDS). Adiponectin and resistin serum levels were significantly elevated in patients with alcohol dependence at both dates (admission and after 1 week of treatment) compared to healthy controls. Adiponectin decreased significantly during the course of withdrawal (T=3.44, p=0.001) while resistin serum levels showed a slight increase (T=-1.83, p=0.071). In a multivariate approach the extent of alcohol craving was significantly associated with adiponectin but not with resistin serum levels in male patients (Beta=-0.255, p=0.025). Results for female patients were not significant. Our findings provide first evidence for an alteration of the adipocytokines adiponectin and resistin during alcohol withdrawal. Furthermore, adiponectin may be involved in the neurobiology of alcohol craving, possibly via its effects on the hypothalamic circuits.


Subject(s)
Adiponectin/blood , Alcoholism/blood , Alcoholism/psychology , Resistin/blood , Adult , Alcoholism/rehabilitation , Analysis of Variance , Enzyme-Linked Immunosorbent Assay , Female , Humans , Male , Middle Aged , Psychiatric Status Rating Scales , Sex Characteristics
2.
Alcohol Clin Exp Res ; 31(12): 1963-7, 2007 Dec.
Article in English | MEDLINE | ID: mdl-18034691

ABSTRACT

Evidence is growing that appetite regulating peptides such as leptin and ghrelin, but also other hormones including prolactin are altered in alcoholism. The brain pro-opiomelanocortin (POMC) system which has important mediating roles in alcohol intake also has important functions in prolactin regulation and energy homeostasis. Furthermore, it has been demonstrated to be functionally integrated with leptin regulation. The satiety factor leptin seems to be counteracted by the gut-derived peptide ghrelin which increases hunger and food intake. Consequently, the POMC system may have a role in integrating regulation of alcohol effects and these seemingly disparate regulatory systems. The goal of this mini-review is to discuss the results of some recent investigations of the potential interactions of these systems with acute and chronic alcohol responses.


Subject(s)
Alcohol Drinking/physiopathology , Alcoholism/physiopathology , Drive , Ghrelin/physiology , Leptin/physiology , Motivation , Pro-Opiomelanocortin/physiology , Prolactin/physiology , Alcohol Drinking/psychology , Alcoholism/psychology , Alcoholism/rehabilitation , Appetite , Brain/physiopathology , Humans , Hypothalamo-Hypophyseal System/physiopathology , Pituitary-Adrenal System/physiopathology , Substance Withdrawal Syndrome/physiopathology , Substance Withdrawal Syndrome/psychology
3.
Alcohol Clin Exp Res ; 31(6): 950-4, 2007 Jun.
Article in English | MEDLINE | ID: mdl-17433008

ABSTRACT

BACKGROUND: A role of appetite-regulating peptides like leptin and ghrelin in the neurobiology of alcohol craving has been proposed by several studies. Aim of this analysis was to search for differences regarding an association between these peptides and alcohol craving with respect to different subtypes and beverage consumption patterns in patients with alcohol dependence. METHODS: We analyzed a sample of 188 patients at admission for alcohol detoxification regarding leptin and ghrelin (n=117) serum levels. Craving was measured using the Obsessive Compulsive Drinking Scale (OCDS). Patients were classified according to Lesch's typology of alcohol dependence and according to their preferred type of alcoholic beverage (beer, wine, spirits). RESULTS: Using general linear models to analyze a possible interaction between subtypes and leptin/ghrelin levels with respect to craving, we found a significant positive association for leptin in patients of Lesch's types 1 and 2, and in patients consuming beer or wine. Ghrelin levels showed a significant trend regarding an association with craving in patients of Lesch's type 1. In the other subgroups we found no significant results. CONCLUSIONS: Our findings show that appetite-regulating peptides may be of special importance regarding alcohol craving in subtypes of patients. This may explicate at least in part previous contradictory findings.


Subject(s)
Alcohol Drinking/physiopathology , Alcoholism/physiopathology , Leptin/physiology , Peptide Hormones/physiology , Adult , Alcoholism/classification , Appetite Regulation/physiology , Female , Ghrelin , Humans , Linear Models , Male , Middle Aged
5.
Psychoneuroendocrinology ; 32(1): 87-90, 2007 Jan.
Article in English | MEDLINE | ID: mdl-17095166

ABSTRACT

Recent studies have described an association of leptin serum levels and craving in alcohol dependent patients. The aim of the present study was to investigate a large patients' sample using a power-based statistical analysis. We included 156 male and 33 female patients suffering from alcohol dependence admitted for detoxification treatment. Leptin serum levels were measured using a commercial ELISA kit. The Obsessive Compulsive Drinking Scale (OCDS) was used to assess alcohol craving at admission. For both genders Spearman's correlation revealed significant results. These findings could be confirmed using multiple linear regression models (males: r=1.881, t=4.338, p<0.001; females: r=6.160, t=5.793, p<0.001) with a power of 1.00. In contrast to previous results describing an association only in female patients, this power-based analysis shows that leptin is associated with alcohol craving in both genders.


Subject(s)
Alcoholism/psychology , Leptin/physiology , Obsessive Behavior/blood , Adult , Alcohol Drinking/blood , Alcoholism/blood , Body Mass Index , Female , Humans , Leptin/blood , Male , Middle Aged
6.
Alcohol Clin Exp Res ; 29(12): 2154-7, 2005 Dec.
Article in English | MEDLINE | ID: mdl-16385185

ABSTRACT

BACKGROUND: The neuropeptides leptin and ghrelin are involved in the appetite regulating network consisting of distinct orexigenic (ghrelin) and anorexigenic (leptin) circuitries. Recently, it has been shown that elevated leptin levels are associated with alcohol craving in patients suffering from alcoholism. Therefore, the aim of the present pilot study was to determine whether the gut-derived peptide ghrelin which increases hunger and food intake is altered and associated with alcohol craving in alcoholic patients METHODS: Two types of alcoholic inpatients, group A (active drinker, acutely intoxicated, n=97) and group B (early abstainer, who had stopped drinking 24-72 hrs before, n=21) were consecutively included in a prospective study from the first day of hospitalization. Ghrelin plasma levels and craving data were assessed on days 0, 1, 2 and 7(-10) and compared to those of 24 healthy controls RESULTS: At each time-point ghrelin plasma levels of alcoholic patients were significantly increased compared to healthy subjects. Furthermore, early abstainers showed significantly higher ghrelin levels than active drinkers. In the group of active drinkers ghrelin plasma levels were significantly increased at each time point compared to baseline. No correlations were found between ghrelin levels and craving data measured by the visual analogue scale or the Obsessive Compulsive Drinking Scale CONCLUSIONS: Ghrelin levels are elevated in alcoholism and seem to further increase during alcohol withdrawal. However, ghrelin levels do not seem to be associated with alcohol craving.


Subject(s)
Alcoholism/blood , Alcoholism/psychology , Peptide Hormones/blood , Adult , Body Mass Index , Central Nervous System Depressants/blood , Ethanol/blood , Female , Ghrelin , Humans , Inpatients , Male , Middle Aged , Obsessive-Compulsive Disorder/psychology , Psychiatric Status Rating Scales , Sample Size , Substance Withdrawal Syndrome/blood , Substance Withdrawal Syndrome/psychology
7.
Kidney Int ; 68(4): 1583-9, 2005 Oct.
Article in English | MEDLINE | ID: mdl-16164635

ABSTRACT

BACKGROUND: High glucose up-regulates the mesangial cell expression of p27(Kip1), an inhibitor of cyclin-dependent kinases/cyclin complexes. Previous in vitro studies using cultured mesangial cells from p27(Kip1-/-) mice demonstrated that these cells do not undergo high glucose-mediated cellular hypertrophy. Since glomerular hypertrophy is an early feature of diabetic nephropathy and may precede the development of glomerulosclerosis, interference with p27(Kip1) expression may attenuate diabetic nephropathy. However, it is unclear whether deletion of p27(Kip1) protects the kidneys of diabetic nephropathy in vivo. METHODS: Type 1 diabetes mellitus was induced in p27(Kip1+/+), p27(Kip1+/-), and p27(Kip1-/-) mice by injection of streptozotocin (STZ). Mice were studied for 6 weeks. Animals injected with citrate buffer only served as controls. At the end of the experiments, urine was collected, albuminuria was determined with an enzyme-linked immunosorbent assay (ELISA), and blood glucose concentrations were measured. Kidneys were perfusion-fixed for quantitative morphologic analysis with glutaraldehyde and for immunohistochemical studies with formaldehyde. Glomerular cell number and volume were analyzed. Glomerulosclerosis, tubulointerstitial, and vascular damage indices were semiquantitatively assessed according to standard methodology. Quantitative glomerular parameters (cell numbers and volumes of endothelial, mesangial, and epithelial cells) were measured on semithin sections. Expression of transforming growth factor-beta1 (TGF-beta1), laminin, and collagen type IV were determined by immunohistochemical staining. RESULTS: In contrast to animals only injected with citrate buffer, mice that received STZ developed hyperglycemia. There was no significant difference in the degree of hyperglycemia among p27(Kip1+/+), p27(Kip1+/-), and p27(Kip1-/-) mice. Diabetic p27(Kip1+/+), but not control p27(Kip1+/+) animals, developed albuminuria. Albuminuria was significantly reduced in diabetic p27(Kip1+/-) and more profoundly in p27(Kip1-/-) animals. Diabetic p27(Kip1+/+) mice revealed a significant increase in mean glomerular volume at 6 weeks. The volumes of mesangial and endothelial cells and podocytes all increased, whereas cell numbers were reduced, consistent with cell hypertrophy. Glomerular, endothelial, mesangial and podocyte hypertrophy were reduced in diabetic p27(Kip1+/-) and p27(Kip1-/-) animals. Diabetic p27(Kip1) (+/+) animals had significantly increased glomerulosclerosis, tubulointerstium, and vascular damage indices compared to nondiabetic p27(Kip1+/+) controls. Diabetic p27(Kip1-/-) mice exhibited significantly less structural damage than diabetic wild-type animals. Diabetic p27(Kip1+/-) animals revealed intermediate glomerulosclerosis, tubulointerstium, and vascular damage values. Immunohistological stainings demonstrated increases in TGF-beta1, collagen type IV, and laminin expression in kidneys of diabetic p27(Kip1+/+) animals compared to nondiabetic p27(Kip1+/+) controls. Staining intensity for type IV collagen and laminin, but not for TGF-beta1, was significantly lower in diabetic p27(Kip1-/-) mice. CONCLUSION: Deletion of p27(Kip1) attenuates the functional and morphologic features of diabetic nephropathy. Although deletion of p27(Kip1) abolished some parameters of diabetic glomerular hypertrophy, the significant reduction of TGF-beta1 expression in the tubulointerstitium indicates that other protective mechanisms could be operative. The p27(Kip1) gene is haplo-insufficient because diabetic p27(Kip1)+/- mice exhibited an intermediate degree of functional and structural renal injury. Our data shows that p27(Kip1) plays an important role in diabetic nephropathy.


Subject(s)
Cyclin-Dependent Kinase Inhibitor p27/genetics , Diabetic Nephropathies/genetics , Diabetic Nephropathies/physiopathology , Albuminuria/genetics , Albuminuria/metabolism , Albuminuria/physiopathology , Animals , Collagen Type IV/metabolism , Cyclin-Dependent Kinase Inhibitor p27/metabolism , Diabetes Mellitus, Type 1/genetics , Diabetes Mellitus, Type 1/metabolism , Diabetes Mellitus, Type 1/physiopathology , Diabetic Nephropathies/metabolism , Extracellular Matrix Proteins/metabolism , Female , Haplotypes , Heterozygote , Kidney Glomerulus/metabolism , Laminin/metabolism , Male , Mice , Mice, Inbred C57BL , Mice, Knockout
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