BACKGROUND
the mechanisms of action of appetite hormones and related networks operating on body weight control have not been entirely established in mammals; the study of these pathways in models of mutant rodents, is contributing to elucidate the issue.
in particular, the obese ob/ob mouse, mutant for the leptin  gene, is currently used to evaluate the pathogenesis of human obesity and type  <dig> diabetes: it lacks the functional leptin, develops hyperphagia, insulin resistance, hyperglycemia and hypercholesterolemia together altered immune response, impaired locomotor activity and fertility  <cit> .
leptin release from adipose cells is stimulated by insulin and glucocorticoids while counter-regulatory hormones inhibit its secretion  <cit> .
in the hypothalamus, leptin exerts a double action: it up-regulates the release of anorexigenic neuropeptides as melanotropic hormone , cart  and crh  while inhibiting secretion of orexigenic neuropeptide y , mch , orexins, and agrp , all signals that, at the opposite, increases appetite and reduces energy consumption.
thus, ob/ob mice present a significant impairment of leptin-dependent hypothalamic pathways, accompanied by adrenal hypertrophy and increased corticosteroid secretion during diurnal rhythms  <cit> .
the use of ob/ob animals has shown the involvement of catecholamines and serotonin  in the leptin-deficient syndrome: in mutant animals, dopaminergic agonists reduce food intake and restrain metabolic dysfunctions, while ssri antidepressant treatment decreases hyperphagia and hyperglycemia  <cit> .
some authors have observed a reduced expression of 5-ht transporter  mrna in dorsal raphe nuclei of ob/ob animals accompanied by an altered locomotor activity  <cit> .
despite all these evidences, to our knowledge, there are still controversial opinions concerning the existence of interactions between leptin, 5-ht transmission and stress signals.
the aim of this study was therefore to investigate the expression of two pivotal proteins involved in 5-ht transmission and metabolism, sert and the translocator protein , in central and peripheral tissues of ob/ob mice in comparison with wild-type  animals.
sert was evaluated given that it modulates the 5-ht re-uptake inside serotonergic neurons, a key mechanism permitting the activation/desensitization of 5-ht receptors within the synaptic cleft.
sert is also localized in periphery where it regulates platelet aggregation, gut peristalsis and immune response.
an altered sert has been reported in several complex human disorders, such as psychiatric diseases, pain and eating disturbances  <cit> .
density and affinity values of the tspo protein were instead investigated as potential markers of stress-response and cholesterol metabolism in ob/ob obese mice.
the tspo protein is in fact the mitochondrial import of cholesterol with binding sites for benzodiazepines  <cit> , also implicated in steroidogenesis  <cit> .
the tspo molecular complex is prevalently located on the mitochondrial membrane and is formed by: the main subunit, the isoquinolinic binding protein , the benzodiazepine binding portion vdac  and the adenine nucleotide translocator ant, which is also a target for benzodiazepines.
associated components of the complex are star  and pap <dig>  proteins, implicated in the steroidogenesis process  <cit> .
nonetheless, the precise function of tspo is unknown  <cit> .
tspo has been indeed related to a variety of biological functions and processes, such as protection against reactive oxygen species, regulation of cell apoptosis, immunity and porphyrin transport  <cit> .
moreover, tspo expression has been found changed in several diseases and pathological conditions  <cit> , including psychiatric diseases and fibromyalgia where altered densities of both sert and tspo have been reported  <cit> .
sert and tspo proteins were thus appraised by means of binding assays carried out in either neuronal or peripheral districts of ob/ob and wt mice.
sert was measured through the high-affinity ssri ligand -paroxetine on brain and platelets, whereas tspo was assessed by the isoquinilinic compound -pk <dig> on brain and kidney.
we also performed autoradiographic studies on limbic-hypothalamic coronal sections of mouse brain.
some previous works have in fact shown changes in sert and 5-ht receptor subtypes at the level of the hypothalamus and limbic areas of mice fatten by a palatable diet  <cit> .
plasma chemical analyses were carried out in animals to evaluate their metabolic state.
RESULTS
analysis of blood chemical parameters
as shown in table  <dig>  ob/ob mice had higher levels of total cholesterol, glucose and high-density-lipoprotein  in comparison with wt mice.
concerning the other blood parameters examined, no relevant between-genotype difference was reported.
γ-gt enzyme activity did not exceed  <dig> u lt- <dig>  in ob/ob and mutant animals, indicating a normal hepatic function in all mice.
: data are presented as mean ± sd  of measures carried out in plasma samples separated from n =  <dig> ob/ob and n =  <dig> wt animals as indicated in the methods section.
-paroxetine and -pk <dig> binding parameters
-paroxetine scatchard analysis revealed a single population of high-affinity binding sites in all membrane preparations.
-paroxetine equilibrium binding experiments , showed no significant difference in either sert density  or affinity  in both brain and platelets of ob/ob vs wt animals .
: data are presented as mean ± sd of n =  <dig> separate experiments in brain or platelet membrane preparations carried out in ob/ob and wt animals as indicated in the methods section.
-pk <dig> binding scatchard analysis also fitted with a single population of high-affinity sites in brain and kidneys.
as shown in table  <dig>  no variation of -pk <dig> binding affinity  was observed in brain and kidneys  of different animals, whilst a significant increased bmax was observed in the ob/ob brain .
kidney bmax resulted unchanged from comparison analysis of the two genotypes.
figure  <dig> depicts a representative linear transformation scatchard, analysis obtained in brain membranes from ob/ob and wt mice, displaying an increased tspo number in mutant animals.
: data are presented as mean ± sd of n =  <dig> separate experiments in brain and kidney membrane preparations carried out in ob/ob and wt animals as indicated in the methods sections.
: student t-test, p <  <dig> .
autoradiography of brain coronal sections
discussion
since many years, the ob/ob mouse is conceived as a suitable experimental model for studying neuropeptide substrates and metabolic pathways implicated in human obesity and type  <dig> diabetes  <cit> : these rodents bear a nonsense mutation in the coding region of the leptin gene causing the lack of secretion of a functional peptide.
an important aspect should be considered when using this mutant model: human obesity is rarely due to a single gene mutation  <cit>  and obese humans prevalently present high circulating levels of leptin  <cit>  together desensitized, leptin-resistant pathways; by contrast, ob/ob mice are defective in leptin production.
differences between these two conditions have not been still elucidated at the biochemical level.
the ob/ob syndrome can be reversed by exogenous administration of leptin or by leptin gene transfection  <cit> , proving that leptin receptors and networks are functional.
on the other side, the study of ob/ob mice permits to dissect leptin-dependent neuroendocrine loops, involved in appetite control and energy balance dysfunctions.
indeed, as already mentioned, leptin pathways, co-modulation or connection with corticotropin releasing factor , npy, α-msh and neurotransmitter systems have not been fully characterized  <cit> .
specifically, energy expenditure balance and feeding behavior are regulated by redundant pathways: monoamines and leptin are both able to modulate food intake at the hypothalamic levels, but it is not precisely known if and how these signal molecules interact  <cit> .
some authors also consider leptin a signal evolved to prevent starvation rather than food plenty  <cit> .
beside alterations of glucose metabolism, another important feature of the ob/ob syndrome is the increased blood cholesterol in mutant animals.
cholesterol is the precursor of steroidogenesis, being a main, high-affinity ligand for the benzodiazepine site-translocator protein tspo  <cit> .
reduced cholesterol levels have been evidenced inside macrophages of ob/ob mice, along with a diminished capacity in inflammatory response  <cit> , supporting metabolic and hormonal cross-talks between immune response, inflammation and body weight signals  <cit> .
interestingly, platelet tspo and sert densities have been found altered in fibromyalgia  <cit> , panic disorders  <cit>  and suicide attempters  <cit> .
this prompted us to preliminary assess the equilibrium-binding parameters of sert and tspo proteins, either in brain or high expression peripheral tissues, circulating platelets and kidneys, of ob/ob mice: to our knowledge, this is the first study that simultaneously evaluates sert and tspo expression in distinct anatomical district of a rodent genetic model of obesity.
prior to sert and tspo analyses, blood chemical parameters were determined in ob/ob and wt animals to monitor cell metabolism: higher total cholesterol and glucose concentrations were observed in mutant vs. wt animals, according to data provided by the commercial source.
blood levels of the γ-gt enzyme were low in ob/ob and wt mice, indicating the absence of hepatic alterations.
moreover, ob/ob mice presented similar circulating triglyceride or calcium levels to those measured in wt animals.
concerning binding results, no difference of sert density or affinity was reported in brain and platelets of ob/ob and control mice.
also, -paroxetine autoradiographic sections showed no appreciable binding differences between animals.
this finding could signify that leptin-dependent pathways are altered in ob/ob mice without affecting 5-ht transmission.
on the other hand, the fact that ob/ob mice show no changes in sert density or affinity  but a reduced sert mrna  <cit>  is intriguing.
since leptin has been found able to decrease sert binding sites in the rat brain  <cit> , the ob/ob mouse could maintain the capacity at counteracting the decrease of sert transcripts at the protein level, in the absence of sert  gene mutations.
in fact, sert underlies posttranslational regulation, trafficking or protein inactivation causing a differential distribution within cell compartments and/or discrepancies between mrna and protein expression, as reported during megakaryoblastic differentiation  <cit> .
leptin-lacking mice could present an altered 5-ht responsiveness together a modified sert reserve/function , without significant differences in binding sites.
a deeper biochemical analysis of sert should be therefore carried out, including flow cytofluorimetry, immunoprecipitation, gene expression, proteomic-functional  studies, in the context of 5-ht  levels in blood and tissues of these animals.
concerning tspo binding results, this protein was found increased in the ob/ob mouse brain while being similar in kidneys of mutant and wt animals.
the pk <dig> autoradiography of hippocampal-hypothalamic sections has revealed an up-regulation of tspo density in two brain regions of ob/ob mice, the dentate gyrus of hippocampus and choroids plexus, indicating that tspo number variations in ob/ob mouse brain are region-dependent.
these results also underline that leptin chronic deficiency affects brain protein patterns.
the interpretation of our tspo finding is difficult.
in fact, to date, the precise role of tspo within cns is not understood.
a brain region-specific regulatory mechanism in response to hypercholesterolemia and hyperglycemia could be active in these animals.
brain tspo is mainly localized on glial cells and can be modulated by protein kinase c signaling  <cit>  and the camp-protein kinase a pathway  <cit> , activated by g-protein coupled receptors, including, therefore, metabotropic 5-ht receptor subtypes.
in hippocampus and choroids plexus there could be an unbalance of regulatory signaling cascades, resulting in the enhancement of tspo number.
this could depend upon many factors, such as different receptor sub-type localization and activation: hippocampus and choroids plexus are brain regions at high expression of 5-ht <dig> and 5-ht2c receptors, respectively, and insulin inhibits choroids plexus 5-ht2c receptors  <cit> .
additional difficulties in interpreting our result come from the observation that increased tspo has been associated with either tissue/neuronal damage or repair.
some authors have reported protective effects of tspo agonists in experimental diabetic neuropathy  <cit> , suggesting, hypothetically, reparative actions of brain tspo in such a disease.
the same as for sert, a deeper study of tspo gene and protein expression together the investigation of its function and drug activities in ob/ob animals by means of different methodologies, including leptin treatment, is essential to confirm present results as well as to understand leptin-dependent neuronal trophism, metabolism and transmission.
another variable to consider is the different age of mutant animals: in our study,  <dig> month old mice were examined, when all symptoms of the "leptin-lacking syndrome" are present  <cit> , but this does not exclude the diverse sert and tspo expression at other development or aging stages.
CONCLUSIONS
present results indicate that leptin-lacking mutant mice have an augmented density of tspo in the hippocampus and choroids plexus, without changes of sert protein number.
central tspo variations are not paralleled by changes in periphery .
despite limitations due to the small sample of animals investigated, our study indicates that the obese ob/ob mouse can be a challenging animal model to elucidate the mammalian leptin-dependent neuroendocrine-neurosteroid signaling involved in appetite control.

 the mechanisms of action of appetite hormones and related networks operating on body weight control have not been entirely established in mammals; the study of these pathways in models of mutant rodents, is contributing to elucidate the issue. in particular, the obese ob/ob mouse, mutant for the leptin gene, is currently used to evaluate the pathogenesis of human obesity and type diabetes: it lacks the functional leptin, develops hyperphagia, insulin resistance, hyperglycemia and hypercholesterolemia together altered immune response, impaired locomotor activity and fertility. leptin release from adipose cells is stimulated by insulin and glucocorticoids while counter-regulatory hormones inhibit its secretion. in the hypothalamus, leptin exerts a double action: it up-regulates the release of anorexigenic neuropeptides as melanotropic hormone, cart and crh while inhibiting secretion of orexigenic neuropeptide y, mch, orexins, and agrp, all signals that, at the opposite, increases appetite and reduces energy consumption. thus, ob/ob mice present a significant impairment of leptin-dependent hypothalamic pathways, accompanied by adrenal hypertrophy and increased corticosteroid secretion during diurnal rhythms. the use of ob/ob animals has shown the involvement of catecholamines and serotonin in the leptin-deficient syndrome: in mutant animals, dopaminergic agonists reduce food intake and restrain metabolic dysfunctions, while ssri antidepressant treatment decreases hyperphagia and hyperglycemia. some authors have observed a reduced expression of 5-ht transporter mrna in dorsal raphe nuclei of ob/ob animals accompanied by an altered locomotor activity. despite all these evidences, to our knowledge, there are still controversial opinions concerning the existence of interactions between leptin, 5-ht transmission and stress signals. the aim of this study was therefore to investigate the expression of two pivotal proteins involved in 5-ht transmission and metabolism, sert and the translocator protein, in central and peripheral tissues of ob/ob mice in comparison with wild-type animals. sert was evaluated given that it modulates the 5-ht re-uptake inside serotonergic neurons, a key mechanism permitting the activation/desensitization of 5-ht receptors within the synaptic cleft. sert is also localized in periphery where it regulates platelet aggregation, gut peristalsis and immune response. an altered sert has been reported in several complex human disorders, such as psychiatric diseases, pain and eating disturbances. density and affinity values of the tspo protein were instead investigated as potential markers of stress-response and cholesterol metabolism in ob/ob obese mice. the tspo protein is in fact the mitochondrial import of cholesterol with binding sites for benzodiazepines, also implicated in steroidogenesis. the tspo molecular complex is prevalently located on the mitochondrial membrane and is formed by: the main subunit, the isoquinolinic binding protein, the benzodiazepine binding portion vdac and the adenine nucleotide translocator ant, which is also a target for benzodiazepines. associated components of the complex are star and pap proteins, implicated in the steroidogenesis process. nonetheless, the precise function of tspo is unknown. tspo has been indeed related to a variety of biological functions and processes, such as protection against reactive oxygen species, regulation of cell apoptosis, immunity and porphyrin transport. moreover, tspo expression has been found changed in several diseases and pathological conditions, including psychiatric diseases and fibromyalgia where altered densities of both sert and tspo have been reported. sert and tspo proteins were thus appraised by means of binding assays carried out in either neuronal or peripheral districts of ob/ob and wt mice. sert was measured through the high-affinity ssri ligand -paroxetine on brain and platelets, whereas tspo was assessed by the isoquinilinic compound -pk on brain and kidney. we also performed autoradiographic studies on limbic-hypothalamic coronal sections of mouse brain. some previous works have in fact shown changes in sert and 5-ht receptor subtypes at the level of the hypothalamus and limbic areas of mice fatten by a palatable diet. plasma chemical analyses were carried out in animals to evaluate their metabolic state.  analysis of blood chemical parameters as shown in table ob/ob mice had higher levels of total cholesterol, glucose and high-density-lipoprotein in comparison with wt mice. concerning the other blood parameters examined, no relevant between-genotype difference was reported. γ-gt enzyme activity did not exceed u lt- in ob/ob and mutant animals, indicating a normal hepatic function in all mice.: data are presented as mean ± sd of measures carried out in plasma samples separated from n = ob/ob and n = wt animals as indicated in the methods section. -paroxetine and -pk binding parameters -paroxetine scatchard analysis revealed a single population of high-affinity binding sites in all membrane preparations. -paroxetine equilibrium binding experiments, showed no significant difference in either sert density or affinity in both brain and platelets of ob/ob vs wt animals.: data are presented as mean ± sd of n = separate experiments in brain or platelet membrane preparations carried out in ob/ob and wt animals as indicated in the methods section. -pk binding scatchard analysis also fitted with a single population of high-affinity sites in brain and kidneys. as shown in table no variation of -pk binding affinity was observed in brain and kidneys of different animals, whilst a significant increased bmax was observed in the ob/ob brain. kidney bmax resulted unchanged from comparison analysis of the two genotypes. figure depicts a representative linear transformation scatchard, analysis obtained in brain membranes from ob/ob and wt mice, displaying an increased tspo number in mutant animals.: data are presented as mean ± sd of n = separate experiments in brain and kidney membrane preparations carried out in ob/ob and wt animals as indicated in the methods sections.: student t-test, p <. autoradiography of brain coronal sections discussion since many years, the ob/ob mouse is conceived as a suitable experimental model for studying neuropeptide substrates and metabolic pathways implicated in human obesity and type diabetes: these rodents bear a nonsense mutation in the coding region of the leptin gene causing the lack of secretion of a functional peptide. an important aspect should be considered when using this mutant model: human obesity is rarely due to a single gene mutation and obese humans prevalently present high circulating levels of leptin together desensitized, leptin-resistant pathways; by contrast, ob/ob mice are defective in leptin production. differences between these two conditions have not been still elucidated at the biochemical level. the ob/ob syndrome can be reversed by exogenous administration of leptin or by leptin gene transfection, proving that leptin receptors and networks are functional. on the other side, the study of ob/ob mice permits to dissect leptin-dependent neuroendocrine loops, involved in appetite control and energy balance dysfunctions. indeed, as already mentioned, leptin pathways, co-modulation or connection with corticotropin releasing factor, npy, α-msh and neurotransmitter systems have not been fully characterized. specifically, energy expenditure balance and feeding behavior are regulated by redundant pathways: monoamines and leptin are both able to modulate food intake at the hypothalamic levels, but it is not precisely known if and how these signal molecules interact. some authors also consider leptin a signal evolved to prevent starvation rather than food plenty. beside alterations of glucose metabolism, another important feature of the ob/ob syndrome is the increased blood cholesterol in mutant animals. cholesterol is the precursor of steroidogenesis, being a main, high-affinity ligand for the benzodiazepine site-translocator protein tspo. reduced cholesterol levels have been evidenced inside macrophages of ob/ob mice, along with a diminished capacity in inflammatory response, supporting metabolic and hormonal cross-talks between immune response, inflammation and body weight signals. interestingly, platelet tspo and sert densities have been found altered in fibromyalgia, panic disorders and suicide attempters. this prompted us to preliminary assess the equilibrium-binding parameters of sert and tspo proteins, either in brain or high expression peripheral tissues, circulating platelets and kidneys, of ob/ob mice: to our knowledge, this is the first study that simultaneously evaluates sert and tspo expression in distinct anatomical district of a rodent genetic model of obesity. prior to sert and tspo analyses, blood chemical parameters were determined in ob/ob and wt animals to monitor cell metabolism: higher total cholesterol and glucose concentrations were observed in mutant vs. wt animals, according to data provided by the commercial source. blood levels of the γ-gt enzyme were low in ob/ob and wt mice, indicating the absence of hepatic alterations. moreover, ob/ob mice presented similar circulating triglyceride or calcium levels to those measured in wt animals. concerning binding results, no difference of sert density or affinity was reported in brain and platelets of ob/ob and control mice. also, -paroxetine autoradiographic sections showed no appreciable binding differences between animals. this finding could signify that leptin-dependent pathways are altered in ob/ob mice without affecting 5-ht transmission. on the other hand, the fact that ob/ob mice show no changes in sert density or affinity but a reduced sert mrna is intriguing. since leptin has been found able to decrease sert binding sites in the rat brain, the ob/ob mouse could maintain the capacity at counteracting the decrease of sert transcripts at the protein level, in the absence of sert gene mutations. in fact, sert underlies posttranslational regulation, trafficking or protein inactivation causing a differential distribution within cell compartments and/or discrepancies between mrna and protein expression, as reported during megakaryoblastic differentiation. leptin-lacking mice could present an altered 5-ht responsiveness together a modified sert reserve/function, without significant differences in binding sites. a deeper biochemical analysis of sert should be therefore carried out, including flow cytofluorimetry, immunoprecipitation, gene expression, proteomic-functional studies, in the context of 5-ht levels in blood and tissues of these animals. concerning tspo binding results, this protein was found increased in the ob/ob mouse brain while being similar in kidneys of mutant and wt animals. the pk autoradiography of hippocampal-hypothalamic sections has revealed an up-regulation of tspo density in two brain regions of ob/ob mice, the dentate gyrus of hippocampus and choroids plexus, indicating that tspo number variations in ob/ob mouse brain are region-dependent. these results also underline that leptin chronic deficiency affects brain protein patterns. the interpretation of our tspo finding is difficult. in fact, to date, the precise role of tspo within cns is not understood. a brain region-specific regulatory mechanism in response to hypercholesterolemia and hyperglycemia could be active in these animals. brain tspo is mainly localized on glial cells and can be modulated by protein kinase c signaling and the camp-protein kinase a pathway, activated by g-protein coupled receptors, including, therefore, metabotropic 5-ht receptor subtypes. in hippocampus and choroids plexus there could be an unbalance of regulatory signaling cascades, resulting in the enhancement of tspo number. this could depend upon many factors, such as different receptor sub-type localization and activation: hippocampus and choroids plexus are brain regions at high expression of 5-ht and 5-ht2c receptors, respectively, and insulin inhibits choroids plexus 5-ht2c receptors. additional difficulties in interpreting our result come from the observation that increased tspo has been associated with either tissue/neuronal damage or repair. some authors have reported protective effects of tspo agonists in experimental diabetic neuropathy, suggesting, hypothetically, reparative actions of brain tspo in such a disease. the same as for sert, a deeper study of tspo gene and protein expression together the investigation of its function and drug activities in ob/ob animals by means of different methodologies, including leptin treatment, is essential to confirm present results as well as to understand leptin-dependent neuronal trophism, metabolism and transmission. another variable to consider is the different age of mutant animals: in our study, month old mice were examined, when all symptoms of the "leptin-lacking syndrome" are present, but this does not exclude the diverse sert and tspo expression at other development or aging stages.  present results indicate that leptin-lacking mutant mice have an augmented density of tspo in the hippocampus and choroids plexus, without changes of sert protein number. central tspo variations are not paralleled by changes in periphery. despite limitations due to the small sample of animals investigated, our study indicates that the obese ob/ob mouse can be a challenging animal model to elucidate the mammalian leptin-dependent neuroendocrine-neurosteroid signaling involved in appetite control. 
by -pk autoradiography of coronal hypothalamic-hippocampal sections, an increased tspo signal was detected in the dentate gyrus and choroids plexus of ob/ob mice, without appreciable changes in the cortex or hypothalamic-thalamic regions. binding studies were thus carried out in brain or peripheral tissues, blood platelets and kidneys, of ob/ob and wt mice supplied with a standard diet, using the selective radiochemical ligands -paroxetine and -pk we observed comparable sert number or affinity in brain and platelets of ob/ob and wt mice, whilst a significantly higher -pk density was reported in the brain of ob/ob animals. unchanged sert in mutant mice is discussed herein in the context of previous literature as the forerunner to a deeper biochemical investigation. these findings show that tspo expression is up-regulated in cerebral regions of ob/ob leptin-deficient mice, suggesting a role of the translocator protein in leptin-dependent cns trophism and metabolism. the present study sought at examining the density and affinity of two proteins related to neurotransmission and cell metabolism, the serotonin transporter sert and the cholesterol import-benzodiazepine site tspo, in a rodent leptin-lacking mutant, the obese ob/ob mouse.
 an ever growing body of evidences is emerging concerning metabolism hormones, neurotransmitters or stress-related biomarkers as effective modulators of eating behavior and body weight in mammals. the present study sought at examining the density and affinity of two proteins related to neurotransmission and cell metabolism, the serotonin transporter sert and the cholesterol import-benzodiazepine site tspo, in a rodent leptin-lacking mutant, the obese ob/ob mouse. binding studies were thus carried out in brain or peripheral tissues, blood platelets and kidneys, of ob/ob and wt mice supplied with a standard diet, using the selective radiochemical ligands -paroxetine and -pk  we observed comparable sert number or affinity in brain and platelets of ob/ob and wt mice, whilst a significantly higher -pk density was reported in the brain of ob/ob animals. tspo binding parameters were similar in the kidneys of all tested mice. by -pk autoradiography of coronal hypothalamic-hippocampal sections, an increased tspo signal was detected in the dentate gyrus and choroids plexus of ob/ob mice, without appreciable changes in the cortex or hypothalamic-thalamic regions.  these findings show that tspo expression is up-regulated in cerebral regions of ob/ob leptin-deficient mice, suggesting a role of the translocator protein in leptin-dependent cns trophism and metabolism. unchanged sert in mutant mice is discussed herein in the context of previous literature as the forerunner to a deeper biochemical investigation. 