Basal and glucoprivic-induced changes in extracellular GABA in the ventral hypothalamus of Zucker rats

1996 ◽  
Vol 271 (2) ◽  
pp. R388-R392 ◽  
Author(s):  
S. E. Specter ◽  
B. A. Horwitz ◽  
J. L. Beverly
Keyword(s):  
Food Intake ◽  
Brain Regions ◽  
Gabaergic System ◽  
Aminobutyric Acid ◽  
Zucker Rats ◽  
Gamma Aminobutyric Acid ◽  
Zucker Rat ◽  
Obese Rats ◽  
Before And After ◽  
Induced Changes

The diminished sensitivity of genetically obese (fa/ fa) Zucker rats to the glucoprivic agent 2-deoxy-D-glucose (2-DG) may involve impaired release of the neurotransmitter gamma-aminobutyric acid (GABA) in discrete regions of the hypothalamus. Extracellular GABA concentrations in the medial (MH) and lateral (LH) hypothalamus of lean (Fa/Fa) and age-matched obese (fa/fa) male Zucker rats before and after 2-DG (1.2 mmol/kg i.v.). Basal GABA concentrations were higher (P < 0.05) in the MH of obese vs. lean rats. No differences were noted in LH GABA levels between lean and obese rats or in baseline extracellular GABA levels between brain regions in lean rats. In lean rats, a characteristic bimodal increase in GABA concentrations was apparent in the MH, whereas GABA concentrations decreased in the LH during the 60 min after 2-DG. No changes in GABA concentrations in dialysate from the MH or LH of obese rats were observed after 2-DG. The alterations in basal activity and responsiveness to glucoprivic stimuli by GABAergic system in the MH of obese rats may reflect a defect in central glucostatic control of food intake and, ultimately, in the hypothesized autonomic imbalance in fa/fa Zucker rat.

scholarly journals Alterations in Rat Accumbens Dopamine, Endocannabinoids and GABA Content During WIN55,212-2 Treatment: The Role of Ghrelin

2020 ◽  
Vol 22 (1) ◽  
pp. 210
Author(s):  
Chrysostomos Charalambous ◽  
Marek Lapka ◽  
Tereza Havlickova ◽  
Kamila Syslova ◽  
Magdalena Sustkova-Fiserova
Keyword(s):  
Nucleus Accumbens ◽  
Food Intake ◽  
Dopamine Release ◽  
Brain Regions ◽  
Aminobutyric Acid ◽  
Gamma Aminobutyric Acid ◽  
Nucleus Accumbens Shell ◽  
Gaba Content ◽  
Dopamine Efflux

The endocannabinoid/CB1R system as well as the central ghrelin signalling with its growth hormone secretagogoue receptors (GHS-R1A) are importantly involved in food intake and reward/reinforcement processing and show distinct overlaps in distribution within the relevant brain regions including the hypothalamus (food intake), the ventral tegmental area (VTA) and the nucleus accumbens (NAC) (reward/reinforcement). The significant mutual interaction between these systems in food intake has been documented; however, the possible role of ghrelin/GHS-R1A in the cannabinoid reinforcement effects and addiction remain unclear. Therefore, the principal aim of the present study was to investigate whether pretreatment with GHS-R1A antagonist/JMV2959 could reduce the CB1R agonist/WIN55,212-2–induced dopamine efflux in the nucleus accumbens shell (NACSh), which is considered a crucial trigger impulse of the addiction process. The synthetic aminoalklylindol cannabinoid WIN55,212-2 administration into the posterior VTA induced significant accumbens dopamine release, which was significantly reduced by the 3 mg/kg i.p. JMV2959 pretreatment. Simultaneously, the cannabinoid-increased accumbens dopamine metabolic turnover was significantly augmented by the JMV2959 pretreament. The intracerebral WIN55,212-2 administration also increased the endocannabinoid arachidonoylethanolamide/anandamide and the 2-arachidonoylglycerol/2-AG extracellular levels in the NACSh, which was moderately but significantly attenuated by the JMV2959 pretreatment. Moreover, the cannabinoid-induced decrease in accumbens γ-aminobutyric acid/gamma-aminobutyric acid levels was reversed by the JMV2959 pretreatment. The behavioural study in the LABORAS cage showed that 3 mg/kg JMV2959 pretreatment also significantly reduced the systemic WIN55,212-2-induced behavioural stimulation. Our results demonstrate that the ghrelin/GHS-R1A system significantly participates in the rewarding/reinforcing effects of the cannabinoid/CB1 agonist that are involved in cannabinoid addiction processing.

Blood flow to brown fat in lean and obese adrenalectomized Zucker rats

1986 ◽  
Vol 251 (5) ◽  
pp. R851-R858
Author(s):  
S. J. Wickler ◽  
B. A. Horwitz ◽  
J. S. Stern
Keyword(s):  
Blood Flow ◽  
Weight Gain ◽  
Brown Fat ◽  
Zucker Rats ◽  
Zucker Rat ◽  
Nonshivering Thermogenesis ◽  
Brown Adipose ◽  
Obese Rats

The Zucker obese rat is characterized by decreased capacity for diet-induced and for nonshivering thermogenesis. This decrease is due, in large part, to reduced thermogenesis in depots of brown adipose tissue, a major source of heat production in rats. Adrenalectomy retards the weight gain observed in the obese rats and also normalizes brown fat guanosine 5'-diphosphate (GDP) binding, an in vitro measure of brown fat thermogenic capacity. This study examined the effect of adrenalectomy on brown fat blood flow, an in vivo measure of the tissue's function, and on norepinephrine-induced O2 consumption (NST) of 11-wk-old obese (fa/fa) and lean (Fa/?) rats. Adrenalectomy had little effect on weight gain, NST, or norepinephrine-stimulated blood flow to brown fat in lean rats. However, adrenalectomy produced profound changes in the obese animals, preventing the weight gain normally occurring in the obese rats and normalizing both NST capacity and norepinephrine-stimulated blood flow to brown fat. These findings provide further support for the importance of brown fat thermogenesis and glucocorticoids in modulating the obesity of the Zucker rat.

scholarly journals Heterogeneity in expression of functional ionotropic glutamate and GABA receptors in astrocytes across brain regions: insights from the thalamus

2014 ◽  
Vol 369 (1654) ◽  
pp. 20130602 ◽  
Author(s):  
Simon Höft ◽  
Stephanie Griemsmann ◽  
Gerald Seifert ◽  
Christian Steinhäuser
Keyword(s):  
Ampa Receptors ◽  
Indirect Effects ◽  
Gaba Receptors ◽  
Brain Regions ◽  
Aminobutyric Acid ◽  
Gamma Aminobutyric Acid ◽  
Functional Heterogeneity ◽  
Rt Pcr ◽  
Ventrobasal Thalamus ◽  
The Impact

Astrocytes may express ionotropic glutamate and gamma-aminobutyric acid (GABA) receptors, which allow them to sense and to respond to neuronal activity. However, so far the properties of astrocytes have been studied only in a few brain regions. Here, we provide the first detailed receptor analysis of astrocytes in the murine ventrobasal thalamus and compare the properties with those in other regions. To improve voltage-clamp control and avoid indirect effects during drug applications, freshly isolated astrocytes were employed. Two sub-populations of astrocytes were found, expressing or lacking α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors. AMPA receptor-bearing astrocytes displayed a lower Kir current density than cells lacking the receptors. In contrast, all cells expressed GABA A receptors. Single-cell RT-PCR was employed to identify the receptor subunits in thalamic astrocytes. Our findings add to the emerging evidence of functional heterogeneity of astrocytes, the impact of which still remains to be defined.

scholarly journals Mechanism controlling sleep organization of the obese Zucker rats

1998 ◽  
Vol 84 (1) ◽  
pp. 253-256 ◽  
Author(s):  
David Megirian ◽  
Jacek Dmochowski ◽  
Gaspar A. Farkas
Keyword(s):  
Eye Movement ◽  
Rem Sleep ◽  
Nrem Sleep ◽  
Zucker Rats ◽  
Rapid Eye Movement ◽  
Zucker Rat ◽  
Obese Zucker Rat ◽  
Obese Rats ◽  
Obese Zucker Rats ◽  
The Mean

Megirian, David, Jacek Dmochowski, and Gaspar A. Farkas. Mechanism controlling sleep organization of the obese Zucker rat. J. Appl. Physiol. 84(1): 253–256, 1998.—We tested the hypothesis that the obese ( fa/fa) Zucker rat has a sleep organization that differs from that of lean Zucker rats. We used the polygraphic technique to identify and to quantify the distribution of the three main states of the rat: wakefulness (W), non-rapid-eye-movement (NREM), and rapid-eye-movement (REM) sleep states. Assessment of states was made with light present (1000–1600), at the rats thermoneutral temperature of 29°C. Obese rats, compared with lean ones, did not show significant differences in the total time spent in the three main states. Whereas the mean durations of W and REM states did not differ statistically, that of NREM did ( P = 0.046). However, in the obese rats, the frequencies of switching from NREM sleep to W, which increased, and from NREM to REM sleep, which decreased, were statistically significantly different ( P = 0.019). Frequency of switching from either REM or W state was not significantly different. We conclude that sleep organization differs between lean and obese Zucker rats and that it is due to a disparity in switching from NREM sleep to either W or REM sleep and the mean duration of NREM sleep.

scholarly journals Gene expression of lipid storage-related enzymes in adipose tissue of the genetically obese Zucker rat. Co-ordinated increase in transcriptional activity and potentiation by hyperinsulinaemia

1992 ◽  
Vol 281 (3) ◽  
pp. 607-611 ◽  
Author(s):  
I Dugail ◽  
A Quignard-Boulangé ◽  
X Le Liepvre ◽  
B Ardouin ◽  
M Lavau
Keyword(s):  
Adipose Tissue ◽  
Mrna Level ◽  
Lipid Storage ◽  
Zucker Rats ◽  
Transcriptional Level ◽  
Transcription Rate ◽  
Mrna Levels ◽  
Zucker Rat ◽  
Obese Zucker Rat ◽  
Obese Rats

The genetically obese Zucker rat displays excessive fat storage capacity which is due to a tissue-specific increase in the activities of a number of lipid storage-related enzymes in adipose tissue. The aim of this study was to investigate the molecular mechanism responsible for this phenomenon. Lean (Fa/fa) and obese (fa/fa) Zucker rats were studied during the early stages of adipose tissue overdevelopment, both before (at 16 days of age) and after (at 30 days of age) the emergence of hyperinsulinaemia, in order to delineate the effects of the fatty genotype independently of those of hyperinsulinaemia. Lipoprotein lipase (LPL), glycerophosphate dehydrogenase (GPDH), glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and malic enzyme (ME) mRNA levels in the adipose tissue of lean and obese rats were assessed by Northern blot analysis, and the relative transcription rates of the corresponding genes were compared in the two genotypes by a nuclear run-on assay. In normoinsulinaemic 16-day-old pre-obese rats, mRNA levels were increased over control values (LPL, 5-fold; ME, 2-fold; GAPDH, 3-fold), in close correlation with genotype-mediated differences in enzyme activities. Stimulation of the transcription rates of the ME and GAPDH genes was observed in obese rats, which could fully account for differences in steady-state mRNA levels. At this age, GPDH activity, mRNA level and transcription rate were similar in the two genotypes. In hyperinsulinaemic 30-day-old obese rats, a 6-7-fold increase in both mRNA and the transcription rate of GPDH emerged, together with an amplification of the genotype-mediated differences observed in younger animals (GAPDH, 6-fold; ME, 7.9-fold; LPL, 10-fold). These results demonstrate that the obese genotype exerts a co-ordinated control on the expression of these genes in adipose tissue, mainly at the transcriptional level. This genotype effect is greatly amplified by the development of hyperinsulinaemia.

scholarly journals Adipsin mRNA amounts are not decreased in the genetically obese Zucker rat

1989 ◽  
Vol 257 (3) ◽  
pp. 917-919 ◽  
Author(s):  
I Dugail ◽  
X Le Liepvre ◽  
A Quignard-Boulangé ◽  
J Pairault ◽  
M Lavau
Keyword(s):  
Gene Expression ◽  
High Fat Diet ◽  
Zucker Rats ◽  
Zucker Rat ◽  
Obese Mice ◽  
High Fat ◽  
Adult Rats ◽  
Obese Zucker Rat ◽  
Obese Rats ◽  
Obese Zucker Rats

Adipsin gene expression as assessed by mRNA amounts was examined in adipose tissue of genetically obese rats at the onset (16 days of age) or at later stages (30 and 60 days of age) of obesity. Amounts of mRNA were equivalent in obese and lean rats at 16 days of age. In adult rats, we observed a 2-fold decrease in adipsin mRNA in the obese rats compared with control lean rats, which was abolished by weaning the animals on a high-fat diet. Our data show that, in sharp contrast with genetically obese mice, adipsin mRNA is not suppressed in genetically obese Zucker rats.

Gamma-Aminobutyric Acid (GABA) in the CSF of Schizophrenic Patients Before and After Neuroleptic Treatment

1978 ◽  
Vol 132 (2) ◽  
pp. 145-148 ◽  
Author(s):  
D. Lichtshtein ◽  
J. Dobkin ◽  
R. P. Ebstein ◽  
J. Biederman ◽  
R. Rimon ◽  
...  
Keyword(s):  
Significant Decline ◽  
Aminobutyric Acid ◽  
Control Group ◽  
Gamma Aminobutyric Acid ◽  
Neuroleptic Treatment ◽  
Normal Individuals ◽  
Significant Difference ◽  
Before And After ◽  
Schizophrenic Patients ◽  
Drug Free

Gamma-aminobutyric acid (GABA) levels in the CSF were measured in 9 normal individuals, 17 drug-free schizophrenic patients and 10 of these same schizophrenic patients after neuroleptic treatment. There was no significant difference between CSF level of GABA in the control group compared to those in schizophrenic patients; however, 6 of the 7 lowest GABA levels were from schizophrenic patients. There was a significant decline of 12 per cent in mean GABA levels in the CSF after a mean of two months of neuroleptic treatment.

Leptin receptor-deficient obese Zucker rats reduce their food intake in response to hypobaric hypoxia

2006 ◽  
Vol 290 (3) ◽  
pp. E591-E597 ◽  
Author(s):  
Nadine Simler ◽  
Alexandra Grosfeld ◽  
André Peinnequin ◽  
Michèle Guerre-Millo ◽  
André-Xavier Bigard
Keyword(s):  
Gene Expression ◽  
Body Weight ◽  
Adipose Tissue ◽  
Food Intake ◽  
Hypobaric Hypoxia ◽  
Leptin Receptor ◽  
Zucker Rats ◽  
Hypoxia Exposure ◽  
Obese Rats ◽  
Hypothalamic Neuropeptides

Exposure to hypoxia induces anorexia in humans and rodents, but the role of leptin remains under discussion and that of orexigenic and anorexigenic hypothalamic neuropeptides remains unknown. The present study was designed to address this issue by using obese (Leprfa/Leprfa) Zucker rats, a rat model of genetic leptin receptor deficiency. Homozygous lean (LeprFA/LeprFA) and obese (Leprfa/Leprfa) rats were randomly assigned to two groups, either kept at ambient pressure or exposed to hypobaric hypoxia for 1, 2, or 4 days (barometric pressure, 505 hPa). Food intake and body weight were recorded throughout the experiment. The expression of leptin and vascular endothelial growth factor (VEGF) genes was studied in adipose tissue with real-time quantitative PCR and that of selected orexigenic and anorexigenic neuropeptides was measured in the hypothalamus. Lean and obese rats exhibited a similar hypophagia (38 and 67% of initial values at day 1, respectively, P < 0.01) and initial decrease in body weight during hypoxia exposure. Hypoxia led to increased plasma leptin levels only in obese rats. This resulted from increased leptin gene expression in adipose tissue in response to hypoxia, in association with enhanced VEGF gene expression. Increased hypothalamic neuropeptide Y levels in lean rats 2 days after hypoxia exposure contributed to accounting for the enhanced food consumption. No significant changes occurred in the expression of other hypothalamic neuropeptides involved in the control of food intake. This study demonstrates unequivocally that altitude-induced anorexia cannot be ascribed to anorectic signals triggered by enhanced leptin production or alterations of hypothalamic neuropeptides involved in anabolic or catabolic pathways.

scholarly journals Metabolic profiling of muscle contraction in lean compared with obese rodents

2010 ◽  
Vol 299 (3) ◽  
pp. R926-R934 ◽  
Author(s):  
John P. Thyfault ◽  
Melanie G. Cree ◽  
Edward B. Tapscott ◽  
Jill A. Bell ◽  
Timothy R. Koves ◽  
...  
Keyword(s):  
Zucker Rats ◽  
Lipid Profiling ◽  
Obese Rats ◽  
Chain Acyl ◽  
Obese Zucker Rats ◽  
Sparing Effect ◽  
Lactate Levels ◽  
Gastrocnemius Muscles ◽  
Induced Changes ◽  
The Impact

Interest in the pathophysiological relevance of intramuscular triacylglycerol (IMTG) accumulation has grown from numerous studies reporting that abnormally high glycerolipid levels in tissues of obese and diabetic subjects correlate negatively with glucose tolerance. Here, we used a hindlimb perfusion model to examine the impact of obesity and elevated IMTG levels on contraction-induced changes in skeletal muscle fuel metabolism. Comprehensive lipid profiling was performed on gastrocnemius muscles harvested from lean and obese Zucker rats immediately and 25 min after 15 min of one-legged electrically stimulated contraction compared with the contralateral control (rested) limbs. Predictably, IMTG content was grossly elevated in control muscles from obese rats compared with their lean counterparts. In muscles of obese (but not lean) rats, contraction resulted in marked hydrolysis of IMTG, which was then restored to near resting levels during 25 min of recovery. Despite dramatic phenotypical differences in contraction-induced IMTG turnover, muscle levels of diacylglycerol (DAG) and long-chain acyl-CoAs (LCACoA) were surprisingly similar between groups. Tissue profiles of acylcarnitine metabolites suggested that the surfeit of IMTG in obese rats fueled higher rates of fat oxidation relative to the lean group. Muscles of the obese rats had reduced lactate levels immediately following contraction and higher glycogen resynthesis during recovery, consistent with a lipid-associated glucose-sparing effect. Together, these findings suggest that contraction-induced mobilization of local lipid reserves in obese muscles promotes β-oxidation, while discouraging glucose utilization. Further studies are necessary to determine whether persistent oxidation of IMTG-derived fatty acids contributes to systemic glucose intolerance in other physiological settings.

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