Accuracy of skeletal scintigraphy for the evaluation of mandibular growth disorders: a systematic review.

Bone scans, reflecting blood flow and metabolic activity in a region of interest, are frequently used to evaluate mandibular growth disorders. Increased uptake is a non-specific finding and can occur as a result of multiple causes. The correlation between radioactive tracer uptake and growth activity has not been consistently demonstrated. The aim of this study was to assess the accuracy of planar skeletal scintigraphy (SS), single-photon emission computed tomography (SPECT), and SPECT with computed tomography (CT) images (SPECT/CT) in detecting abnormal mandibular growth activity compared to clinical and radiographic/tomographic methods (reference standard) and histologic findings. A systematic review was conducted following the PRISMA guidelines. Sensitivity, specificity, and accuracy were calculated for planar SS, SPECT, and SPECT/CT. Compared to the reference standard, SPECT/CT had the best diagnostic accuracy (76.5% sensitivity, 90.4% specificity, 83.2% accuracy), followed by planar SS (81.8% sensitivity, 84.5% specificity, 83.0% accuracy) and SPECT (77.7% sensitivity, 72.4% specificity, 74.5% accuracy). The results of this study indicate that SPECT/CT has the best clinical correlation, but the certainty of the evidence is low. The differences in sensitivity and specificity between the three index tests were not clinically significant. The three tests can be useful, with only a small difference in their diagnostic value. Histopathology was found not to be satisfactory as a reference standard.

Association of craniomaxillofacial fractures and blunt cerebrovascular injuries.

High energy trauma has been considered a risk factor for blunt cerebrovascular injuries (BCVI). The purpose of this study was to determine the incidence and risk factors for BCVI specifically in patients with maxillofacial fractures in an urban level I trauma center. A retrospective cohort study of patients aged ≥ 18 years, admitted to Massachusetts General Hospital (MGH) between 2007 and 2017, was implemented. There were 23,394 patients treated and entered into the MGH Trauma Registry: 22,287 sustained blunt trauma. Of the total blunt trauma patients, 68 (0.3%) had BCVI. There were 2421 patients with CMF fractures from blunt trauma (mean ± standard deviation age, 53 ± 22 years; 29.9% female included as study subjects, of whom 24 (1.0%) had BCVI). In a multivariate model, all mandible fracture (odds ratio (OR) 4.3, 95% confidence interval (CI) 1.6-11.6, P = 0.004), crush injury, defined as blunt compression injury (OR 11.1, 95% CI 2.1-58.1, P = 0.004), and cervical spine injury (OR 10.1, 95 CI 3.7-27.5, P < 0.001) were independent risk factors for BCVI. Mortality was 4.3 times higher in craniomaxillofacial fracture patients with BCVI versus those without BCVI; complications of BCVI (stroke) contributed to the majority of deaths. Appropriate screening and treatment of BCVI in patients with maxillofacial fractures is important.

Cerebral venous sinus thrombosis as a consequence of shunt hyperdrainage: a proposal of the pathophysiological mechanism and case report.

BACKGROUND AND AIM: Shunt dysfunction is a common event, especially in children who have this intervention performed early in life. The consequences of chronic shunt overdrainage can be multiple since the cerebral hydrodynamics is altered. A thrombotic event with consequent symptoms of intracranial hypertension is discussed in this article. MATERIAL AND METHODS: We performed a detailed review of cerebral hydrodynamics and intracranial pressure compensation mechanisms and how this can alter cerebral venous circulation. Next, we report the case of a 4-year-old child with such a clinical presentation that was conducted by our team. RESULTS: A child with a history of hydrocephalus treated with a ventriculo-peritoneal (VP) shunt in his early childhood presented with symptoms of intracranial hypertension, initial computed tomography (CT) demonstrating reduced-sized ventricles. Complementary investigation showed bilateral papilledema, cranial suture closure, changes compatible with Chiari type I, and venous sinus thrombosis (transverse and sigmoid, bilaterally). The case was managed conservatively with full anticoagulation with enoxaparin. Four months after the onset of symptoms, there was an improvement in the clinical and imaging status. CONCLUSION: A condition of severe headache in a patient with an apparently functioning shunt and small ventricles on initial CT should open up a range of diagnostic possibilities, with pseudotumor cerebri syndrome and cerebral venous sinus thrombosis being suggested. The therapeutic approach in these cases must be individualized.

Renin-angiotensin system blockers regulate the metabolism of isolated fat cells in vitro.

Due to the presence of the renin-angiotensin system (RAS) in tissues and its specific influence on white adipose tissue, fat cells are possible targets of pharmacological RAS blockers commonly used as anti-hypertensive drugs. In the present study, we investigated the effects of different RAS blockers on fat cell metabolism, more specifically on lipolysis, lipogenesis and oxidation of energy substrates. Isolated primary adipocytes were incubated with different RAS blockers (aliskiren, captopril and losartan) in vitro for 24 h and lipolysis, lipogenesis and glucose oxidation capacities were determined in dose-response assays to a ß-adrenergic agonist and to insulin. Although no change was found in lipolytic capacity, the RAS blockers modulated lipogenesis and glucose oxidation in a different way. While captopril decreased insulin-stimulated lipogenesis (-19% of maximal response and -60% of insulin responsiveness) due to reduced glucose derived glycerol synthesis (-19% of maximal response and 64% of insulin responsiveness), aliskiren increased insulin-stimulated glucose oxidation (+49% of maximal response and +292% of insulin responsiveness) in fat cells. Our experiments demonstrate that RAS blockers can differentially induce metabolic alterations in adipocyte metabolism, characterized by a reduction in lipogenic responsiveness or an increase in glucose oxidation. The impact of RAS blockers on adipocyte metabolism may have beneficial implications on metabolic disorders during their therapeutic use in hypertensive patients.

Renin-angiotensin system blockers regulate the metabolism of isolated fat cells in vitro

Due to the presence of the renin-angiotensin system (RAS) in tissues and its specific influence on white adipose tissue, fat cells are possible targets of pharmacological RAS blockers commonly used as anti-hypertensive drugs. In the present study, we investigated the effects of different RAS blockers on fat cell metabolism, more specifically on lipolysis, lipogenesis and oxidation of energy substrates. Isolated primary adipocytes were incubated with different RAS blockers (aliskiren, captopril and losartan) in vitro for 24 h and lipolysis, lipogenesis and glucose oxidation capacities were determined in dose-response assays to a β-adrenergic agonist and to insulin. Although no change was found in lipolytic capacity, the RAS blockers modulated lipogenesis and glucose oxidation in a different way. While captopril decreased insulin-stimulated lipogenesis (−19% of maximal response and −60% of insulin responsiveness) due to reduced glucose derived glycerol synthesis (−19% of maximal response and 64% of insulin responsiveness), aliskiren increased insulin-stimulated glucose oxidation (+49% of maximal response and +292% of insulin responsiveness) in fat cells. Our experiments demonstrate that RAS blockers can differentially induce metabolic alterations in adipocyte metabolism, characterized by a reduction in lipogenic responsiveness or an increase in glucose oxidation. The impact of RAS blockers on adipocyte metabolism may have beneficial implications on metabolic disorders during their therapeutic use in hypertensive patients.

Fat gain with physical detraining is correlated with increased glucose transport and oxidation in periepididymal white adipose tissue in rats

As it is a common observation that obesity tends to occur after discontinuation of exercise, we investigated how white adipocytes isolated from the periepididymal fat of animals with interrupted physical training transport and oxidize glucose, and whether these adaptations support the weight regain seen after 4 weeks of physical detraining. Male Wistar rats (45 days old, weighing 200 g) were divided into two groups (n=10): group D (detrained), trained for 8 weeks and detrained for 4 weeks; and group S (sedentary). The physical exercise was carried out on a treadmill for 60 min/day, 5 days/week for 8 weeks, at 50-60% of the maximum running capacity. After the training protocol, adipocytes isolated from the periepididymal adipose tissue were submitted to glucose uptake and oxidation tests. Adipocytes from detrained animals increased their glucose uptake capacity by 18.5% compared with those from sedentary animals (P<0.05). The same cells also showed a greater glucose oxidation capacity in response to insulin stimulation (34.55%) compared with those from the S group (P<0.05). We hypothesize that, owing to the more intense glucose entrance into adipose cells from detrained rats, more substrate became available for triacylglycerol synthesis. Furthermore, this increased glucose oxidation rate allowed an increase in energy supply for triacylglycerol synthesis. Thus, physical detraining might play a role as a possible obesogenic factor for increasing glucose uptake and oxidation by adipocytes.

Fat gain with physical detraining is correlated with increased glucose transport and oxidation in periepididymal white adipose tissue in rats.

As it is a common observation that obesity tends to occur after discontinuation of exercise, we investigated how white adipocytes isolated from the periepididymal fat of animals with interrupted physical training transport and oxidize glucose, and whether these adaptations support the weight regain seen after 4 weeks of physical detraining. Male Wistar rats (45 days old, weighing 200 g) were divided into two groups (n=10): group D (detrained), trained for 8 weeks and detrained for 4 weeks; and group S (sedentary). The physical exercise was carried out on a treadmill for 60 min/day, 5 days/week for 8 weeks, at 50-60% of the maximum running capacity. After the training protocol, adipocytes isolated from the periepididymal adipose tissue were submitted to glucose uptake and oxidation tests. Adipocytes from detrained animals increased their glucose uptake capacity by 18.5% compared with those from sedentary animals (P<0.05). The same cells also showed a greater glucose oxidation capacity in response to insulin stimulation (34.55%) compared with those from the S group (P<0.05). We hypothesize that, owing to the more intense glucose entrance into adipose cells from detrained rats, more substrate became available for triacylglycerol synthesis. Furthermore, this increased glucose oxidation rate allowed an increase in energy supply for triacylglycerol synthesis. Thus, physical detraining might play a role as a possible obesogenic factor for increasing glucose uptake and oxidation by adipocytes.

What is the impact of low testosterone levels on the anatomical and behavioral repertoire of long-term enriched housing of male mice?

Environmental enrichment is a strategy to improve animal welfare, providing brain plasticity with changes at cellular, molecular and behavioral levels. In order to test the long-term effects of enriched housing and the importance of testosterone levels for the expression of behavioral plasticity, 28 categories were assessed in 45 adult Swiss mice, subdivided in prepubertal castrated and non-castrated groups, maintained for seven months as three non-sibling mates. Enrichment consisted of introducing insets for gnawing, climbing and hiding. Tests of spontaneous exploration (barrier), territoriality (intruder) and hierarchical organization (group) were applied at once. Measurements of body weight and the relative weight of key organs were done at the end of the experiment. Mice kept in enriched cages, either castrated or non-castrated, showed more spontaneous exploration than those raised in standard cages. Non-castrated mice housed in structured cages had a lower frequency of attack in the resident-intruder test than the non-castrated standard caged mice, indicating a decrease in territoriality in the first group. Independent of the housing conditions, castrated mice showed reduction of offensive, defensive, and social contacts, as well as low frequency of attack in both agonistic tests. The well-known importance of testes to ensure the expression of aggressive and social contact behaviors was therefore not challenged by the enrichment condition. Behavioral repertoire at the home cage, performance in the group-test, and organometric measurements were not significantly different between the groups kept in enriched and non-enriched cages. Our results suggest that the experience in enriched environment does not increase aggressiveness in their routine in the home-cage nor negatively influence physiological parameters, independently of the testosterone level.

Hormonal changes and increased anxiety-like behavior in a perimenopause-animal model induced by 4-vinylcyclohexene diepoxide (VCD) in female rats.

Perimenopause, a transition period that precedes menopause, is characterized by neuroendocrine, metabolic and behavioral changes, and is associated with increased vulnerability to affective disorders. The decrease in ovarian follicles during perimenopause contributes to a dynamic and complex hormonal milieu that is not yet well characterized. In rodents, 4-vinylcyclohexene diepoxide (VCD) induces a gradual depletion of ovarian follicles, modeling the transition to menopause in women. This study was aimed to investigate, in VCD-treated rats, the hormonal status and the behavior in the elevated plus-maze (EPM), a widely used test to assess anxiety-like behavior. From the postnatal day 28, rats were treated with VCD or vehicle for 15 days. At 80±5 days after the beginning of treatment the experiments were performed at proestrus and diestrus. In the first experiment rats were decapitated, ovary was collected and blood samples were taken for estradiol, progesterone, follicle stimulant hormone (FSH), testosterone, dihydrotestosterone (DHT) and corticosterone measurements. In the second experiment, rats were subjected to the EPM for 5 min, and behavioral categories recorded. Administration of VCD induced follicular depletion as well as an increase of the number of atretic follicles demonstrating the treatment efficacy. The transitional follicular depletion was accompanied by lower progesterone, testosterone and DHT with no changes in the FSH, estradiol and corticosterone plasma levels. On the EPM, rats showed decreased open arm exploration and increased risk assessment behavior, indicating increased anxiety. These findings show that administration of VCD to induce ovarian failure results in endocrine and anxiety-related changes that are similar to the symptoms exhibited by women during menopause transition. Thus, this model seems to be promising in the study of perimenopause-related changes.

New concepts in white adipose tissue physiology.

Numerous studies address the physiology of adipose tissue (AT). The interest surrounding the physiology of AT is primarily the result of the epidemic outburst of obesity in various contemporary societies. Briefly, the two primary metabolic activities of white AT include lipogenesis and lipolysis. Throughout the last two decades, a new model of AT physiology has emerged. Although AT was considered to be primarily an abundant energy source, it is currently considered to be a prolific producer of biologically active substances, and, consequently, is now recognized as an endocrine organ. In addition to leptin, other biologically active substances secreted by AT, generally classified as cytokines, include adiponectin, interleukin-6, tumor necrosis factor-alpha, resistin, vaspin, visfatin, and many others now collectively referred to as adipokines. The secretion of such biologically active substances by AT indicates its importance as a metabolic regulator. Cell turnover of AT has also recently been investigated in terms of its biological role in adipogenesis. Consequently, the objective of this review is to provide a comprehensive critical review of the current literature concerning the metabolic (lipolysis, lipogenesis) and endocrine actions of AT.

New concepts in white adipose tissue physiology

Numerous studies address the physiology of adipose tissue (AT). The interest surrounding the physiology of AT is primarily the result of the epidemic outburst of obesity in various contemporary societies. Briefly, the two primary metabolic activities of white AT include lipogenesis and lipolysis. Throughout the last two decades, a new model of AT physiology has emerged. Although AT was considered to be primarily an abundant energy source, it is currently considered to be a prolific producer of biologically active substances, and, consequently, is now recognized as an endocrine organ. In addition to leptin, other biologically active substances secreted by AT, generally classified as cytokines, include adiponectin, interleukin-6, tumor necrosis factor-alpha, resistin, vaspin, visfatin, and many others now collectively referred to as adipokines. The secretion of such biologically active substances by AT indicates its importance as a metabolic regulator. Cell turnover of AT has also recently been investigated in terms of its biological role in adipogenesis. Consequently, the objective of this review is to provide a comprehensive critical review of the current literature concerning the metabolic (lipolysis, lipogenesis) and endocrine actions of AT.

Chronic glucocorticoid treatment enhances lipogenic activity in visceral adipocytes of male Wistar rats.

AIM: Glucocorticoid (GC) in excess promotes the redistribution of adipose tissue from peripheral to central sites of the body. In this study, we characterized an experimental condition of prolonged GC excess and investigated its effect on the lipogenic metabolism in white adipose tissue. METHODS: Twenty male Wistar rats were divided into control (CON) and dexamethasone-treated (DEX) groups. DEX group received dexamethasone (0.25 mg kg(-1) day(-1) ) during 4 weeks, while CON group received saline. Animals were killed and subcutaneous (SC), retroperitoneal (RP) and mesenteric (MS) fat pads were excised, weighed and processed for adipocyte isolation, morphometric cell analysis and incorporation of glucose into lipids. RESULTS: The treatment effectively blocked hypothalamic-pituitary-adrenal axis, as verified by a 58% decrease in plasma corticosterone levels and 19% atrophy in adrenal glands in DEX group. Animals from DEX group presented insulin resistance, glucose intolerance, dyslipidaemia and increased insulin and leptin plasma levels and hypertrophied adipocytes. They showed increased lipogenesis in RP and MS depots, with increased incorporation of glucose into fatty acids of triacylglycerol. Increased activity of lipogenic enzymes ATP-citrate lyase, fatty acid synthase, glucose-6-phosphate dehydrogenase and malic was only seen in the MS depot in DEX group, while gene expression of these enzymes was enhanced in SC and MS fat depots. CONCLUSION: The adaptations promoted by GC treatment in adipose metabolism seemed to be mainly due to the increased activity of enzymes that supply the NADPH required for lipogenesis than to the increase in enzymes that more directly deal with fatty acid synthesis itself.

Ovarian steroids decrease DNA fragmentation in the serotonin neurons of non-injured rhesus macaques.

We previously found that ovarian steroids promote neuroprotection in serotonin neurons by decreasing the expression of pro-apoptotic genes and proteins in the dorsal raphe nucleus of rhesus macaques, even in the absence of overt injury. In this study, we questioned whether these actions would lead to a reduction in DNA fragmentation in serotonin neurons. Ovariectomized (OVX) rhesus monkeys were implanted with silastic capsules that were empty (placebo) or containing estradiol (E), progesterone (P) or estradiol and progesterone (E+P) for 1 month. In all animals, eight levels of the dorsal raphe nucleus in a rostral-to-caudal direction were immunostained using the terminal deoxynucleotidyl transferase nick end labeling (TUNEL) method. Two staining patterns were observed, which are referred to as type I, with complete dark staining of the nucleus, and type II, with peripheral staining in the perinuclear area. A montage of the dorsal raphe was created at each level with a Marianas Stereology Microscope and Slidebook 4.2, and the TUNEL-positive cells were counted. In direct comparison with OVX animals, P treatment and E+P treatment significantly reduced the total number of TUNEL-positive cells (Mann-Whitney test, both treatments P=0.04) and E+P treatment reduced the number of TUNEL-positive cells per mm(3) (Mann-Whitney test, P=0.04). Double immunocytochemistry for TUNEL and tryptophan hydroxylase (TPH) indicated that DNA fragmentation was prominent in serotonin neurons. These data suggest that in the absence of ovarian steroids, a cascade of gene and protein expression leads to an increase in DNA fragmentation in serotonin neurons. Conversely, ovarian steroids have a neuroprotective role in the non-injured brain and prevent DNA fragmentation and cell death in serotonin neurons of nonhuman primates.

Stress sensitive female macaques have decreased fifth Ewing variant (Fev) and serotonin-related gene expression that is not reversed by citalopram.

Female cynomolgus monkeys exhibit different degrees of reproductive dysfunction with moderate metabolic and psychosocial stress. When stressed with a paradigm of relocation and diet for 60 days or two menstrual cycles, highly stress resilient monkeys (HSR) continued to ovulate during the stress cycles whereas stress sensitive monkeys (SS) did not. After cessation of stress, monkeys characterized as HSR or SS were administered placebo (PL) or S-citalopram (CIT) for 15 weeks at doses that normalized ovarian steroid secretion in the SS animals and that maintained blood CIT levels in a therapeutic range. After euthanasia, the brain was perfused with 4% paraformaldehyde. The pontine midbrain was blocked and sectioned at 25 microm. The expression of four genes pivotal to serotonin neural function was assessed in the four groups of monkeys (n=4/group). Fev (fifth Ewing variant) ETS transcription factor, tryptophan hydroxylase 2 (TPH2), the serotonin reuptake transporter (SERT), and the 5HT1A autoreceptor were determined at 7-8 levels of the dorsal raphe nucleus with in situ hybridization (ISH) using radiolabeled- and digoxygenin-incorporated riboprobes. Positive pixel area and cell number were measured with Slidebook 4.2 in the digoxigenin assay for Fev. Optical density (OD) and positive pixel area were measured with NIH Image software in the radiolabeled assays for TPH2, SERT and 5HT1A. All data were analyzed with two-way ANOVA. SS monkeys had significantly fewer Fev-positive cells and lower Fev-positive pixel area in the dorsal raphe than HSR monkeys. SS monkeys also had significantly lower levels of TPH2, SERT and 5HT1A mRNAs in the dorsal raphe nucleus than HSR monkeys. However, CIT did not alter the expression of either Fev, TPH2, SERT or 5HT1A mRNAs. These data suggest that SS monkeys have fewer serotonin (5-HT) neurons than HSR monkeys, and that they have deficient Fev expression, which in turn, leads to deficient TPH2, SERT and 5HT1A expression. In addition, the therapeutic effect of CIT is probably achieved through mechanisms other than alteration of 5-HT-related gene expression.

Unique responses of midbrain CART neurons in macaques to ovarian steroids.

CART (cocaine and amphetamine regulated transcript) is a neuropeptide involved in the control of several physiological processes, such as response to psychostimulants, food intake, depressive diseases and neuroprotection. It is robustly expressed in the brain, mainly in regions that control emotional and stress responses and it is regulated by estrogen in the hypothalamus. There is a distinct population of CART neurons located in the vicinity of the Edinger-Westphal nucleus of the midbrain that also colocalize urocortin-1. The aims of this study were 1) to determine the distribution of CART immunoreactive neurons in the monkey midbrain, 2) to examine the effects of estrogen (E) and progesterone (P) on midbrain CART mRNA and peptide expression and 3) to determine whether midbrain CART neurons contain steroid receptors. Adult female rhesus monkeys (Macaca mulatta) were spayed and either treated with placebo (OVX), estrogen alone (E), progesterone alone (P) or E+P. Animals were prepared (a) for RNA extraction followed by microarray analysis and quantitative (q) RT-PCR (n=3/group); (b) for immunohistochemical analysis of CART and CART+tryptophan hydroxylase (TPH), CART+estrogen receptors (ER) or CART+progesterone receptors (n=5/group) and (c) for Western blots (n=3/group). Both E- and E+P-administration decreased CART gene expression on the microarray and with qRT-PCR. Stereological analysis of CART immunostaining at five levels of the Edinger-Westphal nucleus indicated little effect of E or E+P administration on the area of CART immunostaining. However, P administration increased CART-immunopositive area in comparison to the OVX control group with Student's t-test, but not with ANOVA. CART 55-102 detection on Western blot was unchanged by hormone administration. ERbeta and PR were detected in CART neurons and CART fibers appeared to innervate TPH-positive serotonin neurons in the dorsal raphe. In summary, E decreased CART mRNA, but this effect did not translate to the protein level. Moreover, P administration alone had a variable effect on CART mRNA, but it caused an increase in CART immunostaining. Together, the data suggest that CART neurons in the midbrain have a unique steroid response, which may be mediated by nuclear receptors, neuroactive steroids or interneurons.

Design of a sampling plan to detect ochratoxin A in green coffee.

The establishment of maximum limits for ochratoxin A (OTA) in coffee by importing countries requires that coffee-producing countries develop scientifically based sampling plans to assess OTA contents in lots of green coffee before coffee enters the market thus reducing consumer exposure to OTA, minimizing the number of lots rejected, and reducing financial loss for producing countries. A study was carried out to design an official sampling plan to determine OTA in green coffee produced in Brazil. Twenty-five lots of green coffee (type 7 - approximately 160 defects) were sampled according to an experimental protocol where 16 test samples were taken from each lot (total of 16 kg) resulting in a total of 800 OTA analyses. The total, sampling, sample preparation, and analytical variances were 10.75 (CV = 65.6%), 7.80 (CV = 55.8%), 2.84 (CV = 33.7%), and 0.11 (CV = 6.6%), respectively, assuming a regulatory limit of 5 microg kg(-1) OTA and using a 1 kg sample, Romer RAS mill, 25 g sub-samples, and high performance liquid chromatography. The observed OTA distribution among the 16 OTA sample results was compared to several theoretical distributions. The 2 parameter-log normal distribution was selected to model OTA test results for green coffee as it gave the best fit across all 25 lot distributions. Specific computer software was developed using the variance and distribution information to predict the probability of accepting or rejecting coffee lots at specific OTA concentrations. The acceptation probability was used to compute an operating characteristic (OC) curve specific to a sampling plan design. The OC curve was used to predict the rejection of good lots (sellers' or exporters' risk) and the acceptance of bad lots (buyers' or importers' risk).

Light/dark cycle-dependent metabolic changes in adipose tissue of pinealectomized rats.

We investigated the effects of pinealectomy on adipose tissue metabolism at different times of day. Adult male Wistar rats were divided into two groups: pinealectomized and control (sham-operated). Eight weeks after surgery, the animals were killed at three different times (at 8.00 a.m., at 4.00 p.m. and 11.00 p.m.). We collected blood samples for glucose, insulin, corticosterone, and leptin determinations, and periepididymal adipocytes for in vitro insulin-stimulated glucose uptake, oxidation, and incorporation into lipids. Pinealectomy caused insulin resistance as measured by 2-deoxyglucose uptake (a fall of approximately 40 % in the maximally insulin-stimulated rates) accompanied by hypercorticosteronemia at the three time points investigated without changes in plasma insulin an or leptin levels. Furthermore, pinealectomy increased the insulin-induced glucose incorporation into lipids (77 %) at 4.00 p.m. and insulin-induced glucose oxidation in the morning and in the afternoon, while higher rates were observed in the evening and in the morning in control rats. In conclusion, cell responsiveness to insulin was differentially affected by pineal ablation and time of day, and persistent insulin resistance was obtained in pinealectomized rats. We hypothesize that pinealectomy exposes the animal to an inadequate match between energy requirements and fuel mobilization.

Effect of a meal feeding schedule on hepatic glycogen synthesis and gluconeogenesis in rats.

We investigated the effect of a meal feeding schedule (MFS) on food intake, hepatic glycogen synthesis, hepatic capacity to produce glucose and glycemia in rats. The MFS comprised free access to food for a 2-hour period daily at a fixed mealtime (8.00-10.00 a.m.) for 13 days. The control group was composed of rats with free access to food from day 1 to 12, which were then starved for 22 h, refed with a single meal at 8.00-10.00 a.m. and starved again for another 22 h. All experiments were performed at the meal time (i.e. 8.00 a.m.). The MFS group exhibited increased food intake and higher glycogen synthase activity. Since gluconeogenesis from L-glutamine or L-alanine was not affected by MFS, we conclude that the increased food intake and higher glycogen synthase activity contributed to the better glucose maintenance showed by MFS rats at the fixed meal time.

Decreased lipolysis and enhanced glycerol and glucose utilization by adipose tissue prior to development of obesity in monosodium glutamate (MSG) treated-rats.

OBJECTIVE: To determine the metabolic alterations that lead to the neonatal administration of monosodium glutamate (MSG), which results in arrested growth and obesity. ANIMALS AND DESIGN: Wistar rats were injected 5 times, every other day, with 4 g of MSG/kg b.w. or with hyperosmotic saline (controls), within the first 10 days of life, and were studied at the age of 30 days. RESULTS: Body weight was lower, whereas adipocyte lipid content, cell diameter, surface area and volume were higher in MSG rats than in controls. Plasma glucose, insulin, NEFA, glycerol and triglyceride levels, and in vitro production of NEFA by lumbar fat pad pieces incubated under basal conditions or in the presence of epinephrine and epinephrine plus glucose in the media were lower in MSG than in control rats. In the same fat pad pieces, the conversion of 1-14C-glycerol into fatty acids was always enhanced and its conversion into glyceride glycerol was enhanced when incubations were carried out in the presence of epinephrine or glucose. Both the hormone sensitive lipase activity and mRNA expression were lower in adipose tissue from MSG rats. Besides, the number of insulin receptors, lipid synthesis from U14C glucose, 3H-2-deoxy D-glucose uptake and cellular GLUT4 translocation index were higher in adipocytes from MSG rats than from the controls. CONCLUSION: It is proposed that an enhanced insulin sensitivity in 1 month old MSG rats is responsible for the decreased lipolytic activity and enhanced glucose uptake. In addition, the enhanced lipogenesis and glycerol reutilization seen in their adipose tissue, disturbs the normal balance between fat depots breakdown and accumulation in favor of the latter.

Leptin stimulates uncoupling protein-2 mRNA expression and Krebs cycle activity and inhibits lipid synthesis in isolated rat white adipocytes.

The treatment of rats and mice with leptin causes dramatic body fat reduction and in some cases even disappearance of fat tissue. Here, we report the effects of leptin (10 and 100 ng.mL-1) on isolated rat adipocytes maintained for 15 h in culture. Leptin decreased the incorporation of acetate into total lipids by 30%. A reduction in this incorporation (42%) was still observed after the leptin-cultivated adipocytes were exposed to a supra-physiological insulin concentration (10 000 microU.mL-1). On the other hand, leptin increased acetate degradation by 69% and the maximal activity of citrate synthase by 50% in isolated adipocytes. It also increased oleate degradation by 35 and 50% at concentrations of 10 and 100 ng. mL-1, respectively. Eventually, leptin upregulated the uncoupling protein-2 (UCP2) mRNA level by 63% and had no effect on uncoupling protein-3 (UCP3) mRNA in isolated adipocytes. The upregulation of UCP2 mRNA might have contributed to the stimulation of acetate and fatty acid degradation by leptin. The peripheral effects of leptin observed in this study are in line with the general energy dissipating role postulated for this hormone and for UCP2. They suggest mechanisms by which adipocytes regulate their fat content by an autocrine pathway without the participation of the central nervous system.