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PubMed2000

Research on eating disorders: current status and future prospects.

This report summarizes the main themes addressed at a workshop on research on eating disorders (EDs), which was hosted by the National Institute of Mental Health in December 1998. Both basic behavioral neuroscientists and clinical investigators met in an effort to integrate areas of research and foster collaborations. Considerable advances have been made in understanding the neuroendocrinological mechanisms that regulate appetite and food intake. These achievements are in sharp contrast with the limited progress in elucidating the pathogenesis of EDs and developing effective treatment and preventive interventions. Anorexia nervosa remains a highly morbid condition with the highest mortality of any other psychiatric disorder. Besides acute refeeding techniques, no specific interventions have been proven effective in changing the long-term course of anorexia nervosa. Efficacious treatments exist for bulimia nervosa, but their underutilization calls for research on translating experimental findings into clinical practice. Closer interface between neuroscientists and clinical researchers is required for advancing our understanding of ED pathogenesis and developing effective treatments. Recent studies are suggestive of a substantial genetic contribution to EDs that deserves further investigation. Finally, there is an urgent need to examine risk and protective factors for EDs, on which safe and effective prevention can be built.

Feeding and Eating Disorders↗
PubMed2001

Meal-induced changes in extracellular 5-HT in medial hypothalamus of lean (Fa/Fa) and obese (fa/fa) Zucker rats.

Hypothalamic serotonin (5-HT) is involved in appetite regulation and sympathetic stimulation of thermogenesis. This study tested the hypothesis that the enhanced energetic efficiency of obese Zucker rats involves blunted serotonergic release within the medial hypothalamus (MH). We used microdialysis and HPLC-EC to measure dynamic changes in extracellular 5-HT levels in the MH of 10-13-week-old male lean (Fa/Fa) and obese (fa/fa) Zucker rats before and after a meal. No differences were noted in basal levels of 5-HT between lean and obese rats. Consistent with the suggestion that hypothalamic 5-HT plays a physiological role in feeding, extracellular 5-HT levels increased significantly in both lean and obese rats given a meal. This increase was observed in the 20 min interval in which they ate the 8.1 kcal meal and remained for an additional 60 min. The net release of 5-HT during the meal interval was comparable in the lean (1.46+/-0.38 fmol/microl) and obese (1.21+/-0.82 fmol/microl) rats. However, the 5-HT levels of the leans (1.80+/-0.29 fmol/microl) plateaued in the next 20 min interval, whereas they continued rising (2.74+/-0.53 fmol/microl) in obese rats and were significantly higher than those in the leans during the 40 and 60 min intervals after the meal was presented. This resulted in a total net release during the meal plus the next three 20 min intervals that was significantly higher in obese (9.83+/-1.16 fmol/microl) than in lean (5.59+/-0.85 fmol/microl) rats. Thus, the enhanced energetic efficiency of the obese Zucker rats may not be associated with attenuated serotonin release in response to a meal. Rather their enhanced release of 5-HT in the MH may reflect compensatory mechanisms for the elevated orexigen NPY, the reduction in meal-induced CCK release, and/or a functional resistance to 5-HT.

Animals↗
PubMed2001

The effect of feeding on cerebrospinal fluid corticotropin-releasing hormone levels in humans.

Corticotropin-releasing hormone (CRH) is a neuropeptide thought to play a role in appetite regulation. In this report, we used a serial cerebrospinal fluid (CSF) sampling technique to examine the relationship between CSF CRH, plasma ACTH and cortisol and perceptions of hunger and satiety in fasting and sated volunteers. CSF was withdrawn continuously from 11:00 AM to 5:00 PM via an indwelling subarachnoid catheter. Blood was withdrawn every 10 min via an antecubital vein catheter. Fed subjects received a meal at 1:00 PM. Subjects who were fed had lower post-prandial ratings on hunger scales and higher ratings on satiety scales. Fed subjects also had slightly lower levels of CSF CRH after feeding. Furthermore, fed subjects had higher ACTH and cortisol concentrations in the first 3 h; by the fourth h the opposite was true. Our findings do not support the hypothesis that CNS CRH is a central satiety factor in the human. Instead our findings of slightly diminished CSF CRH levels after feeding may be accounted for by the rises in glucocorticoids and their associated negative feedback effects on CNS CRH. Alternatively, our findings could also reflect changes in CRH levels associated with feeding in multiple brain areas and in the spinal cord with the net effect being in the negative direction.

Adrenocorticotropic Hormone↗
PubMed1998

The effect of hypothalamic peptide YY on hippocampal acetylcholine release in vivo: implications for limbic function in binge-eating behavior.

Central injection of peptide YY (PYY) in sated rats produces the most powerful stimulating effect of food intake known to date. The neural mechanisms by which PYY regulates appetite are not clear but may be important because abnormal levels of PYY have been implicated in the neurobiology of bulimia nervosa. Interactions between brain acetylcholine (ACh) and PYY had not been studied. Therefore, the present experiments were designed to explore the in vivo release of ACh from the hippocampus (HPC) of rats in response to hypothalamic infusion of PYY. Hippocampal ACh release was found to increase 400% in response to 10 microg PYY. In a separate experiment, blockade of the same area of the HPC with bilateral intracerebral injections of 3.5 microg scopolamine did not affect intake stimulated by intrahypothalamic injection of 4 microg PYY. Furthermore, a third experiment showed, for the first time, that PYY (2.5-10.0 microg) can elicit robust feeding when infused directly into the HPC. The significance of these findings to the activation of limbic functions such as memory, reinforcement, and obsessional processes that accompany human binge-eating syndromes is discussed.

Acetylcholine↗
PubMed2000

Pharmacological characterization of the cloned neuropeptide Y y(6) receptor.

Neuropeptide Y has potent appetite stimulating effects which are mediated by hypothalamic receptors believed to be of the neuropeptide Y Y(1) and/or neuropeptide Y Y(5) subtype. In mice, the neuropeptide Y y(6) receptor is also expressed in the hypothalamus, suggesting that it too may function as a feeding receptor in this species. Several laboratories have studied the pharmacology of the neuropeptide Y y(6) receptor, but their results are not in agreement. Using neuropeptide Y and a variety of peptide analogs and small molecule antagonists, we have determined that the pharmacology of the cloned mouse neuropeptide Y y(6) receptor is distinct from that of the other known neuropeptide Y receptors. The rank order of binding affinity for the mouse neuropeptide Y y(6) receptor is [(Ile, Glu,Pro,Dpr,Tyr,Arg,Leu,Arg,Tyr-NH(2))(2)human peptide YY=human, rat neuropeptide Y=human, rat neuropeptide Y-(2-36)=human, rat [Leu(31), Pro(34)porcine (Cys(2))-neuropeptide Y-(1-4)-8-aminooctanoyl-(D-Cys(27)porcine [D-Trp(32)rat pancreatic polypeptide=human pancreatic polypeptide. A similar rank order of potency is seen for inhibition of forskolin-stimulated cyclic AMP. The neuropeptide Y Y(5) receptor antagonist trans-naphthalene-1-sulfonic acid ¿4-[4-amino-quinazolin-2-ylamino)-methyl]-cyclohexylmethy l¿-amide hydrochloride (CGP 71683A) and the neuropeptide Y Y(1) receptor antagonist ((R)-N(2)-diphenylacetyl)-N-[(4-hydroxyphenyl)methyl]-argininam ide) (BIBP3226) bind weakly to the neuropeptide Y y(6) receptor (K(i)10, 000 nM, respectively). Although the function of the neuropeptide Y y(6) receptor remains to be elucidated, its pharmacology is not consistent with a role in appetite regulation.

Animals↗
PubMed1999

Distribution and quantification of immunoreactive orexin A in rat tissues.

A sensitive and specific radioimmunoassay for orexin A was developed. Orexin A immunoreactivity was found to be confined to the central nervous system (CNS) with the highest concentrations in the hypothalamus, inferior and superior colliculi and brainstem. Within the hypothalamus, the highest levels were found in the lateral and posterior hypothalamus. These regions had a greater orexin A content in females compared to males. The orexin A content of hypothalamic regions did not change with fasting and no difference was noted in hypothalami of rats fed a high fat diet. The hypothalamic orexin A content was not different in obese Zucker rats compared to lean controls. Thus, orexin A has a wide distribution in the CNS, but appetite regulation may not be its main function.

Animals↗
PubMed1999

Modulation of taste reactivity by intestinal distension in rats.

Discomfort created by intestinal distension may play a role in controlling intake behavior. We analyzed these effects in details by the taste reactivity test in Long-Evans rats. A balloon inserted into a separated Thiry-Vella intestinal loop was distended with different volumes of water (0.05, 0.09, 0.12, and 0.28 mL, respectively). Saccharin solution (0.001 M) was infused into the mouth via an implanted oral cannula nine times for 30 s, with 5-min intertrial intervals. The balloon was distended after the second and released following the seventh trial. Taste reactivity (TR) elements were videotaped and later analyzed for appetitive and aversive responses. The number of appetitive responses decreased after gut distension, whereas aversive elements were infrequent and stable. It is suggested that pleasantness of the taste stimulus decreased independently of the discomfort, which remained mild but steady; that is, sweet taste gradually lost its hedonic value but was not accompanied by an acquired aversion of the same taste. This finding may point to the difference of the motivational and discriminative effects of the internal stimuli.

Animals↗
PubMed1999

Effects of intracerebroventricularly administered leptin on protein selection in the rat.

The effect of centrally administered rat leptin on selection of 5 and 30% protein diets was investigated in male Sprague-Dawley rats with indwelling i.c.v. cannulas. Leptin (0 vs 2.5 microg/day) was administered for 4 consecutive days, followed by an 8-day withdrawal period. Total intake was reduced to approximately 50% of that in the vehicle injected group during each day following leptin administration. Intake of both the 5 and 30% diets was reduced. Vehicle-treated rats selected a 13-15% CP diet. Diet selection in leptin-treated rats was not different during the first day, but on Days 2-4, leptin-treated rats selected a 10% CP diet. Intake began to normalize within 24-48 h after the last treatment, and was not different by Day 3 of the withdrawal period. Body weight was reduced by leptin treatment, and despite the normalization of food intake, did not recover during the withdrawal period. Rats were sacrificed at the end of the 8-day withdrawal period. Despite the reduction in body and carcass weights, liver, kidney, heart, and soleus muscle weights were not different between control and leptin-treated groups when expressed on an absolute or relative basis. However, epididymal and retroperitoneal fat pad weights were still reduced 56 and 78%, respectively, in rats that had been previously treated with leptin for 4 days and then not treated for 8 days. In addition, circulating T3 levels remained elevated in rats that had been treated with leptin. Centrally administered leptin has little effect on muscle mass, but had potent effects on intake of nonobese rats and a sustained effect on adipose tissue mass, thyroid hormone status, and body weight after withdrawal. Results from rats selecting between diets varying in protein content suggest that leptin may cause avoidance of protein.

Animals↗
PubMed1999

Effects of the 5-HT1A receptor agonist 8-OH-DPAT on operant food intake in food-deprived pigs.

The effects of the 5-HT1A agonist 8-hydroxy-2 (di-n-propylamino)tetralin (8-OH-DPAT) were investigated on operant food intake in food-deprived pigs. In Experiment 1, 8-OH-DPAT (5-20 microg/kg) administered intravenously (i.v.) 15 min prior to the occurrence of feeding produced a dose-related decrease in operant food intake in pigs that had been fasted overnight. The effects were mainly apparent during the first 30 min after the start of the feeding period. In Experiment 2, 8-OH-DPAT (25 and 50 microg/kg, i.v.) administered 60 min prior to the occurrence of feeding in pigs that were fasted overnight also produced significant decreases in food intake. The effects were mainly apparent during the first 30-40 min after the start of the feeding period. In Experiment 3, 8-OH-DPAT (20 microg/kg, i.v.) significantly increased operant feeding in satiated pigs during the first 30 min after administration. These results show that 8-OH-DPAT has complex effects on feeding behaviour in pigs, increasing operant food intake in satiated pigs, while producing a reduction in food intake in food-deprived animals.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMedDate not supplied

Reversal of delta 9-THC hyperphagia by SR141716 and naloxone but not dexfenfluramine.

Presatiated adult male Lister hooded rats received oral administration of the exogenous cannabinoid Delta-9-tetrahydrocannabinol (Delta(9)-THC; 1.0 mg/kg) in combination with subcutaneous injection of either the cannabinoid CB1 antagonist N-piperidino-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methylpyrazole-3-carboxamide (SR141716; 0, 0.05, 0.1, 0.5 or 1.0 mg/kg), the CB2 antagonist N-[(1S)-endo-1,3,3-trimethyl bicyclo[2.2.1]heptan-2-yl]-5-(4-chloro-3-methylphenyl)-1-(4-methylbenzyl)-pyrazole-3-carboxamide (SR144528; 0, 0.05, 0.1, 0.5 or 1.0 mg/kg), the general opioid antagonist naloxone (0.1, 0.5, 1.0 or 5.0 mg/kg) or the 5-HT agonist dexfenfluramine (0.05, 0.1, 0.5, 1.0 or 5.0 mg/kg). Food (chow) intake was measured over 2 h from the onset of the dark period. Delta(9)-THC induced significant hyperphagia, which was attenuated by subanorectic doses of SR141716 and naloxone. Neither SR144528 nor dexfenfluramine affected Delta(9)-THC-induced feeding. These data confirm mediation of Delta(9)-THC hyperphagia by central-type CB1 receptors, and support a functional relationship between cannabinoid and opioid systems in relation to appetite regulation. Stimulation of CB1 receptors may promote feeding by actions on food reward rather than by inhibition of serotonergic satiety mechanisms.

Animals↗
PubMed2003

Nibbling at CRF receptor control of feeding and gastrocolonic motility.

Inadequate pharmacological tools, until recently, hindered the understanding of the roles of corticotropin-releasing factor (CRF) receptor subtypes in appetite regulation and gastrocolonic motor function. Now, novel ligands that are selective for CRF(1) or CRF(2) receptors are helping to uncover the specific functions of CRF receptor subtypes. Central or peripheral CRF(2) receptor activation suppresses feeding independently of CRF(1) receptors. In the rat, central administration of CRF(2) receptor agonists promotes satiation without eliciting the malaise, behavioral arousal or anxiogenesis associated with CRF(1) receptor agonists. Conversely, central administration of CRF(1) receptor agonists elicits short-onset anorexia independently of CRF(2) receptor activation. With respect to gastrointestinal motor function, stress inhibits gastric motility through CRF(2) receptor-dependent central autonomic and peripheral myenteric systems. By contrast, stress stimulates colonic motility via CRF(1) receptor-dependent sacral parasympathetic and colonic myenteric mechanisms. These findings have important physiological implications and suggest targeted approaches for the pharmacotherapy of obesity and stress-related functional gastrointestinal and eating disorders.

Animals↗
PubMed2002

The role of NPY in the mediation of orexin-induced hypothermia.

The mediation of orexin-A-induced hypothermia was investigated. Different doses of orexin-A (140-560 pmol) were administered intracerebroventricularly (i.c.v.) to adult male rats, and the colon temperature was used as an index of the thermoregulatory action. Orexin-A decreased both the basal colon temperature and the lipopolysaccharide-induced fever and exhibited a bell-shaped dose-response curve. I.c.v. pretreatment with neuropeptide Y (NPY) antiserum 24 h before orexin administration significantly decreased the hypothermic effect of orexin-A. These data strengthen the hypothesis that this appetite-regulating peptide might also play a role in thermoregulation, and its hypothermic effect seems to be mediated at least partially by NPY.

Animals↗
PubMed2000

Evidence that NPY Y1 receptors are involved in stimulation of feeding by orexins (hypocretins) in sated rats.

Neuropeptide Y (NPY) produced in the arcuate nucleus (ARC) of the hypothalamus stimulates feeding both directly by activating NPY receptors and indirectly through release of the orexigenic peptides, galanin and beta-endorphin (beta-END), in the paraventricular nucleus (PVN) and surrounding neural sites. Orexin A and orexin B, produced outside the ARC in the lateral hypothalamic area (LH), have recently been shown to stimulate feeding. In the present studies we tested the hypothesis that NPYergic signaling may mediate feeding stimulated by orexins. In adult male rats injected intracerebroventricularly (i.c.v.) with orexin A (3, 10, 15 nmol) or orexin B (3, 10, 30 nmol) feeding was stimulated in a dose-dependent manner; maximal feeding was seen after 15 nmol orexin A and 30 nmol orexin B. To determine whether NPY may mediate this orexin stimulated feeding, we used 1229U91, a selective NPY Y1 receptor antagonist (NPY-A). Whereas NPY-A on its own was ineffective, it suppressed NPY-induced feeding. Furthermore, NPY-A completely blocked the feeding evoked by either orexin A (15 nmol) or orexin B (30 nmol). These results show that orexin A and B stimulate feeding and further suggest that these excitatory effects may be mediated by NPYergic signaling through Y1 receptors. These findings are in accord with the view that the orexin-NPY pathway may comprise a functional link upstream from NPY within the hypothalamic appetite regulating network.

Animals↗
PubMed2001

Origins of the many NPY-family receptors in mammals.

The NPY system has a multitude of effects and is particularly well known for its role in appetite regulation. We have found that the five presently known receptors in mammals arose very early in vertebrate evolution before the appearance of jawed vertebrates 400 million years ago. The genes Y(1), Y(2) and Y(5) arose by local duplications and are still present on the same chromosome in human and pig. Duplications of this chromosome led to the Y(1)-like genes Y(4) and y(6). We find evidence for two occasions where receptor subtypes probably arose before peptide genes were duplicated. These observations pertain to the discussion whether ligands or receptors tend to appear first in evolution. The roles of Y(1) and Y(5) in feeding may differ between species demonstrating the importance of performing functional studies in additional mammals to mouse and rat.

Amino Acid Sequence↗
PubMed1998

Distribution and characterization of enterostatin-like immunoreactivity in human cerebrospinal fluid.

Enterostatins belong to a family of peptides (e.g., Val-Pro-Asp-Pro-Arg, VPDPR; Ala-Pro-Gly-Pro-Arg, APGPR; and Val-Pro-Gly-Pro-Arg, VPGPR) derived from the tryptic cleavage of amino-terminal pentapeptide from procolipase. Pharmacologic studies have suggested a role for these peptides in appetite regulation and insulin secretion. Studies into the distribution of enterostatins or the role of endogenous peptides have not been possible until now due to the lack of a suitable method for assay. Using two polyclonal antibodies raised against VPDPR and APGPR and different chromatographic methods, we have examined the nature and distribution of enterostatin-like immunoreactivity in human cerebrospinal fluid. The results reported here show for the first time the presence of enterostatin-like immunoreactivity in the human cerebrospinal fluid. Further characterization of cerebrospinal fluid enterostatin-like immunoreactivity revealed that it is not due to APGPR, VPGPR, or VPDPR but to another peptide similar to VPDPR.

Adult↗
PubMed1999

On the nature and distribution of enterostatin (Val-Asp-Pro-Asp-Arg)-like immunoreactivity in rat plasma.

Enterostatins, pentapeptides represented at the amino-terminus of the procolipase molecule, are derived following tryptic cleavage of the procolipase molecule in the lumen of the gut. Val-Pro-Asp-Pro-Arg or VPDPR is one such enterostatin. Despite pharmacologic studies suggesting a role for VPDPR in appetite regulation and insulin secretion, the function of this endogenous peptide has been impossible to discern due to the lack of a suitable assay. Using polyclonal antibodies raised against VPDPR and different chromatographic methods, we examined the nature and distribution of enterostatin-like immunoreactivity in rat plasma. The results reported here show for the first time the presence of VPDPR-like immunoreactivity in rat plasma. Further characterization of the plasma VPDPR-like immunoreactivity revealed that a) it is not due to APGPR, VPGPR, or VPDPR but to another peptide similar to VPDPR, and b) plasma VPDPR-like immunoreactivity may circulate bound to large carrier proteins.

Animals↗
PubMed1999

Leptin concentrations in maternal serum and amniotic fluid during the second trimenon: differential relation to fetal gender and maternal morphometry.

Leptin, a hormone produced by adipocytes, provides information on the availability of fat stores to the hypothalamus and acts as an afferent satiety signal regulating appetite and energy expenditure in both rodents and humans [Zhang Y, Proenca R, Maffei M, Barone M, Leopold L, Friedman JM. Positional cloning of the mouse obese gene and its human homologue. Nature 1994;372:425-432; Sinha MK. Human leptin: the hormone of adipose tissue. Eur J Endocrinol 1997;136:461-4; Campfield LA, Smith FJ, Guisez Y, Devos R, Burn P. Recombinant mouse ob protein: evidence for a peripheral signal linking adiposity and central neural networks. Science 1995;269:546-9; Halaas JL, Gajiwala KS, Maffei M, Cohen SL, Chait BT, Rabinowitz D, Lallone RL, Burley SK, Friedman JM. Weight-reducing effects of the plasma protein encoded by the obese gene. Science 1995;269:543-6; Saladin R, De Vos P, Guerre-Millo M, Leturque A, Girard J, Staels B, Auwern J. Transient increase in obese gene expression after food intake or insulin administration. Nature 1995;377:527-9; Campfield LA, Smith FJ, Burn P. The OB protein (leptin) pathway - a link between adipose tissue mass and central neural networks. Horm Metab Res 1996;28:619-632; Blum WF, Kiess W, Rascher W, editors. Leptin - the voice of the adipose tissue. J&J Edition, JA Barth Verlag, Heidelberg, 1997]. In addition, leptin is thought to play an important role for reproduction and during gestation [Kiess W, Blum WF, Aubert ML. Leptin, puberty and reproductive function: lessons from animal studies and observations in humans. Eur J Endocrinol 1997;138:1-4; Barash IA, Cheung CC, Wigle DS, Ren H, Kabitting EB, Kuijer JL, Clifton DK, Steiner RA. Leptin is a metabolic signal to the reproductive system. Endocrinology 1996;133:3144-47; Chehab F, Lim M, Lu R. Correction of the sterility defect in homozygous obese female mice by treatment with the human recombinant leptin. Nature Genetics 1996;12:318-20; Kiess W, Schubring C, Prohaska F, Englaro P, Rascher W, Attanasio A, Blum WF. Leptin in amniotic fluid at term and at midgestation. In: Blum WF, Kiess W, Rascher W, editors. Leptin - the voice of the adipose tissue. J&J Edition, JA Barth Verlag, Heidelberg, 1997]. The purpose of this study was to gain more insight into a putative role of leptin during midgestation. Therefore we have measured leptin concentrations in maternal serum and amniotic fluid using a specific radioimmunoassay (RIA) employing human recombinant leptin for tracer and standard preparation [Blum WF, Kiess W, Rascher W, editors, Leptin - The voice of the adipose tissue. J&J Edition, JA Barth Verlag, Heidelberg, 1997; Blum WF, Englaro P, Heiman M, Attanasio Am, Kiess W, Rascher W. Clinical studies of serum leptin. In: Blum WF, Kiess W, Rascher W. Leptin - The voice of the adipose tissue. J&J Edition, JA Barth Verlag, Heidelberg, 1997; Blum WF, Englaro P, Heiman M, Attanasio AM, Kiess W, Rascher W. Plasma leptin levels in healthy children and adolescents: dependence on body mass index, body fat mass, gender, pubertal stage and testosterone. J Clin Endocrinol Metab 1997;82:2904-2910]. In addition, estriol, hCG and alphafetoprotein were measured in maternal serum. (ABSTRACT TRUNCATED)

Adult↗
PubMed2002

Effects of pro-inflammatory cytokines and chemokines on leptin production in human adipose tissue in vitro.

Leptin is synthesized in adipocytes and acts primarily through central pathways suppressing appetite and increasing the metabolic rate in rodents as well as in humans. Recently leptin has also been suggested to have peripheral effects and be involved in insulin action. Since cytokines and chemokines may have effects on appetite regulation as well as on some of the obesity-related complications e.g. insulin resistance and cardiovascular disease, we investigated the effects of various cytokines and chemokines on leptin production in human adipose tissue fragments in vitro. Abdominal subcutaneous adipose tissue from healthy normal to overweight females was incubated for up to 48 h with the cytokines: tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6) and interleukin-1beta (IL-1beta) and the chemokine: interleukin-8 (IL-8). IL-1beta (50 ng/ml) and TNF-alpha (10 ng/ml) decreased leptin production by 30-50% (P<0.05) and gene expression by 80-90% (P<0.05). In contrast, IL-6 and IL-8 had no effect on either leptin production or leptin gene expression. Interestingly, IL-1beta elicited a biphasic effect on leptin release with an incremental phase observed within 4 h with no concomitant change in leptin gene expression, followed by a long-lasting inhibition of leptin release and leptin gene expression. This could suggest that IL-1beta through a post-translational pathway induced an acute increase in leptin-secretion, perhaps through the release of leptin from a pre-formed pool within the adipose tissue. The long-term decrease in both leptin secretion and transcription could indicate that pro-inflammatory cytokines such as IL-1beta and TNF-alpha might influence the circulating leptin levels and thereby influence the adipose tissue to brain signalling, which could be of importance in relation to the obesity-associated diseases such as insulin resistance and cardiovascular disease.

Adipose Tissue↗