Effects of concurrent exercise on health-related quality of life in middle-aged women.

OBJECTIVE: This study aimed to evaluate the influence of a 16-week concurrent exercise program on health-related quality of life in middle-aged women. METHODS: A total of 150 middle-aged women from the FLAMENCO project (age range 45-60 years) were randomized into a counseling (n = 75) or an exercise (n = 75) group. The exercise group followed a 16-week (3 days/week, 60 min/session) concurrent exercise program (aerobic + resistance training). The counseling group attended conferences on a healthy lifestyle. Participants' health-related quality of life was assessed with the EuroQol plus, a visual analog scale and the 36-item Short Form Health Survey (SF-36), where greater values indicate a better health-related quality of life. RESULTS: The visual analog scale increased by 9.0% in the exercise group, whereas it only increased by 3.5% in the counseling group (p = 0.040). The SF-36 physical function, physical role, bodily pain, vitality and emotional role increased by 5.5%, 11.3%, 10.8%, 9.6% and 8.9%, respectively, in the exercise group, whereas these only increased by 0.6%, decreased by 0.7% and increased by 1.4%, 3.8% and 0.6% in the counseling group (all p < 0.05). CONCLUSIONS: Our results suggest that a 16-week concurrent exercise program adapted for midlife women improved their health-related quality of life. CLINICALTRIALS.GOV IDENTIFIER: NCT02358109. Date of registration: 05/02/2015.

Visual and semi-quantitative analysis of 6-[18F]FDOPA PET/CT in patients with brain tumors and suspected tumor recurrence versus radionecrosis.

INTRODUCTION: Amino acid PET is a tool recommended by the main neuroimaging societies in the differential diagnosis between radionecrosis (RNC) and umour recurrence (TR) in brain tumours, but its use in our country is still limited. The aim of this work is to present our experience with 6-[18F]FDOPA PET/CT (FDOPA) in brain tumours (primary and M1), comparing these results with other published results. MATERIAL AND METHODS: Retrospective study of 62 patients with suspected tumour recurrence (TR): 42 brain metastases (M1) and 20 primary, who underwent FDOPA. Images were analysed visually and semi-quantitatively, obtaining SUVmax and SUVmaxlesion/SUVmaxstriatum (L/S) and SUVmaxlesion/SUVmaxcortex (L/C) ratios. The diagnostic validity of PET was analysed and the best performing cut-off points were calculated. PET results were compared with clinical-radiological follow-up and/or histopathology. RESULTS: TR was identified in 49% of M1 and 76% of brain primaries. The best performing FDOPA interpretation was visual and semi-quantitative, with a sensitivity and specificity in primaries of 94% and 80% and in M1s of 96% and 72% respectively. The cut-off points with the best diagnostic performance were L/C1.44 in M1 and L/C1.55 in primaries. There are discrepant results with other published results. CONCLUSION: FDOPA PET/CT is a useful tool in the differential diagnosis between recurrence and RNC in brain tumours. It is needed a standardization to contribute to homogenise FDOPA results a inter-centre level.

Acute symptomatic seizures and epilepsy after mechanical thrombectomy. A prospective long-term follow-up study.

INTRODUCTION: New treatments for acute ischaemic stroke, such as mechanical thrombectomy, can achieve reperfusion of large ischaemic tissue. Some studies have suggested that reperfusion therapies can increase the risk of suffering acute symptomatic seizure (ASS) and poststroke epilepsy (PSE). The aim of the study was to determine the incidence of ASS and PSE in patients undergoing thrombectomy, and related factors. PATIENTS AND METHODS: This was a retrospective single-centre study including patients with ischaemic stroke and NIHSS> 8 treated with thrombectomy with a follow-up ≥5 years. We evaluated several epidemiological, radiological, clinical and electroencephalographic variables. RESULTS: Of the 344 included patients, 21 (6.1%) presented ASS, 53 (15.40%) died in the acute phase, and 13 (4.46%) died during the first year. The degree of reperfusion (p 0.029), advanced age (p 0.035), and haemorrhagic transformation (p 0.038) increased the risk of suffering ASS, with degree of reperfusion being an independent factor, OR 2.02 (1.21-4.64). The incidence of PSE was 4.12% in the first year, 3.72% in the second, and 1.61% in the fifth. The accumulated incidence at 5 years was 8.93%. Related risk factor for suffering PSE was ASS (p < 0.001), yielding an OR value of 2.00 (1.28-3.145). CONCLUSIONS: Thrombectomy doesn´t increase the risk of ASS. A higher percentage of reperfusion, advanced age, and haemorrhagic transformation are associated with an increased risk of ASS. ASS is a risk factor for suffering PSE. In terms of mortality, having suffered ASS and/or PSE does not increase acute or long-term mortality.

[Historical perspective of the studies with the greatest impact on the treatment of gliomas]. / Perspectiva histórica de los estudios con mayor impacto en el tratamiento de los gliomas.

Historically, advances in our knowledge of neuro-oncology and improvements in the survival of patients with brain tumours have been relatively scarce. One of the main turning points can be established from 2005 onwards, when the potential therapeutic role of cytostatics in these tumours was confirmed, thus changing the standard of treatment. Up until that date, only radiation therapy and surgery were considered truly effective treatments. This shift has contributed to the development of new systemic therapies and to an in-depth study of gliomagenesis. Advances in the knowledge of the basic fields of brain tumours have helped improve the design and results of new clinical trials, while clinical outcomes provide feedback and new data to further the understanding of these tumours. However, these promising advances open up new unresolved questions and offer a critical approach to the interpretation of past studies. This review mainly updates the results of trials that changed or modified the clinical practice of the treatment and management of gliomas. Commenting on relevant basic research papers that have not yet been translated into the implementation of changes in the treatment of these patients is excluded.

TITLE: Perspectiva histórica de los estudios con mayor impacto en el tratamiento de los gliomas.Históricamente, los avances en el área de conocimiento de la neurooncología y las mejoras en la supervivencia de los pacientes con tumores cerebrales han sido relativamente escasos. Uno de los principales puntos de inflexión puede establecerse a partir de 2005, cuando se constata el hasta entonces potencial papel terapéutico de los citostáticos en estos tumores, cambiando consiguientemente el estándar de tratamiento. Hasta esa fecha, sólo la radioterapia y la cirugía se consideraban tratamientos realmente eficaces. Este cambio ha contribuido al desarrollo de nuevas terapias sistémicas y a profundizar en el estudio de la gliomagénesis. Los avances en los campos básicos del conocimiento de los tumores cerebrales han ayudado a mejorar el diseño y los resultados de los nuevos ensayos clínicos, al mismo tiempo que los resultados clínicos retroalimentan y ofrecen nuevos datos para seguir avanzando en la comprensión de estos tumores. Sin embargo, estos esperanzadores avances abren nuevas cuestiones aún no resueltas y ofrecen un enfoque crítico a la interpretación de estudios pasados. La presente revisión principalmente actualiza los resultados de los ensayos que cambiaron o modificaron la práctica clínica del tratamiento y el manejo de los gliomas. Se excluyen trabajos relevantes de investigación básica que aún no han tenido traslación en la implementación de cambios en el tratamiento de estos pacientes.

Mediterranean diet, tobacco consumption and body composition during perimenopause. The FLAMENCO project.

OBJECTIVE: To study the association of the adherence to the Mediterranean diet (MD) and tobacco consumption with body composition during perimenopause. STUDY DESIGN AND METHODS: A cross-sectional study in 176 perimenopausal women from the FLAMENCO project. A food frequency questionnaire and the Mediterranean Diet Score were assessed. Body composition was measured using dual-energy X-ray absorptiometry. MAIN OUTCOMES MEASURES: Body mass index (BMI), fat mass (FM), ratio of gynecoid to total fat mass (G/T), ratio of android to gynecoid fat mass (A/G), visceral adipose tissue (VAT) and waist circumference (WC). RESULTS: Intake of whole-grain cereals was associated with lower WC, FM percentage, android FM, VAT and higher G/T (all p < 0.05). Intake of nuts was associated with lower BMI and FM percentage and intake of fruits with lower BMI, WC, total and android FM, FM percentage, A/G, VAT and higher G/T (all p < 0.05). Intake of pulses was associated with lower weight, BMI and android FM. Intake of whole dairy products was associated with lower weight, BMI, WC, total and android FM and VAT (all p < 0.05). Intake of olive oil was associated with lower WC and FM percentage (all p < 0.05). Intake of sweetened beverages was associated with higher weight, BMI, WC, FM percentage, android FM, VAT and total FM (all, p < 0.05). Smokers had a lower MD adherence (p < 0.05). Finally, a greater MD adherence was associated with higher G/T (p < 0.01) and lower A/G (p < 0.05). CONCLUSIONS: A higher MD adherence, avoiding tobacco, an increased consumption of whole-grain cereals, nuts, fruits, pulses, whole dairy products and olive oil, and a lower consumption of sweetened beverages might contribute to a healthier body composition during perimenopause.

Intestinal oleoyl-estrone esterase activity in the Wistar rat.

Low-dose oral oleoyl-estrone (OE) (i.e. in dairy products) is hydrolysed to estrone, which promotes growth and fat deposition. However, pharmacological doses of OE are absorbed largely intact and elicit fat losses. Thus, in order to find out how the intestine handles OE, esterase activity (at pH 5, 7 or 8) was measured in rat stomach, duodenum, jejunum, ileum, cecum, large intestine, and liver using OE as substrate. There were no sex-related differences. Pure pancreatic cholesterol-ester esterase hydrolysed OE even in the absence of taurocholate. The differences in the pH-related activity distribution pattern and selective inhibition and taurocholate dependence show that, in addition to the luminal (i.e. pancreatic) cholesterol-ester esterase, other esterases hydrolyse OE; these combined activities may be sufficient to rapidly dispose of pharmacological doses of OE. Female rats received a tritium-labeled OE gavage; the luminal and tissue label content were measured up to 24 h. The high retention of label in the stomach suggest that this may be a significant site of absorption. The rapid decrease of label in intestinal lumen (and rat tissues) shortly after the administration, hint at rapid absorption and disposal. In conclusion, the high OE-esterase activity and early absorption of OE are indicative of upper gastro-intestinal tract absorption skipping most of the medium-tract esterases.

The conjugated linoleic acid ester of estrone induces the mobilisation of fat in male Wistar rats.

We investigated whether the substitution of the fatty acid moiety in oleoyl-estrone (OE) by conjugated linoleic acid, i.e. conjugated linoleoyl-estrone (cLE) may help improve the antiobesity effects of OE. Overweight (17% fat) male rats were treated for 10 days with oral OE or cLE (10 nmol/g per day) and compared with controls receiving only the oily vehicle. Rat weight and food intake were measured daily. After killing by decapitation, body composition and main plasma parameters were analysed. cLE induced marked decreases in body weight, energy intake, carcass energy and body lipid, whilst sparing protein; the effects were not significantly different from those obtained with OE. Energy expenditure was unchanged, but energy intake decreased to 46% (OE) or 55% (cLE) of controls; whole body energy decreased by 29% (OE) or 24% (cLE) in the 10-day period studied. Plasma composition showed almost identical decreases in glucose and cholesterol elicited by OE and cLE, with a more marked decrease in triacylglycerols by OE and no effect of either on NEFA. OE decreased leptin and insulin levels, but the effects of cLE were more marked on both, with similar decreases in adiponectin. It can be concluded that cLE is a new drug of the OE family; its overall effects on energy were akin to those of OE, albeit fractionally less effective at the single dose tested. However, this lower potency on lipid mobilisation does not affect other effects, such as powerful hypercholesterolemic effects or the modulation of adiponectin. And last, but not least, cLE seems to produce a more marked decrease in leptin and insulin than OE, which may reflect a coordinate action of the conjugated linoleic acid moiety and the "OE effect" on target tissues. If that were the case, cLE may constitute an improvement over OE in its action on insulin resistance.

In the rat, estrone sulphate is the main serum metabolite of oral oleoyl-estrone.

Two different oral doses of oleoyl-estrone: 1 and 10 nmol/g a day were given once to male Wistar rats. The serum levels of free estrone, estrone sulphate, estradiol, and acyl-estrone were measured at intervals up to 72 h after the gavage. Oleoyl-estrone was rapidly absorbed; with the 1 nmol/g dose no changes were observed in plasma acyl-estrone but levels increased dramatically with 10 nmol/g, peaking at 6 h; high acyl-estrone levels were maintained up to 24 h, returning to normalcy at 48 h. With the 10 nmol/g dose, free estrone at most doubled its levels but estrone sulphate concentrations rose by one order of magnitude; in both cases, the increases soon (2 h) reached a plateau that was maintained for almost two days. Estradiol levels remained unchanged except for a transient peak at 2 h at the 10 nmol/g dose. The relationship between free estrone and its sulphate was linear, and those of estrone and estrone sulphate versus acyl-estrone showed the existence of an upper serum concentration limit for both molecules. The results hint at estrone sulphate being an important metabolite of oleoyl-estrone disposal, confirm the limited estrogenic response to oleoyl-estrone administration and agree with a rapid absorption and disposal of oleoyl-estrone, nevertheless maintaining high circulating levels of the ester for a time after its oral administration.

[Ocular myasthenia gravis: diagnostic aspects and evolution]. / Miastenia grave ocular: aspectos diagnósticos y evolución.

INTRODUCTION: Myasthenia gravis lacks a diagnostic gold standard, so diagnosis is supported by the findings of several tests. Conversion from ocular myasthenia gravis (OMG) to a more widespread disease is frequently early. AIMS. To describe and compare the clinical data and findings of the diagnostic tests of patients with OMG and those with a different diagnosis, and to know the conversion rate from OMG to generalized myasthenia. PATIENTS AND METHODS: Descriptive and analytic retrospective study of 44 patients referred for neurophysiological testing through 4 years because of suspected OMG. RESULTS: 12 patients (27%) were diagnosed as having OMG. Evolution time prior to diagnosis tended to be shorter in OMG patients. Isolated ptosis or combined with diplopia was more frequent in OMG, while isolated diplopia was so in other diagnoses (p = 0.003). No thymoma was found. SFEMG jitter of facial muscles was abnormal, including blocking, in all OMG patients (8/8) and normal in the rest (30/30). Edrophonium test was positive in all OMG patients (7/7) and doubtful in another one (1/7). Anti-AChR titers were initially positive in 10/11 OMG patients and 0/17 with other diagnoses. Aponeurotic ptosis and strabismus were the most frequent non-myasthenic etiologies. OMG showed an early generalization in two patients who developed dysarthria. CONCLUSIONS: The low ratio of diagnostic confirmation suggests that in the face of ptosis or diplopia diagnostic testing with a high sensibility for OMG is favoured. Jitter showed the best initial diagnostic performance.

L-alanine transport in small intestine brush-border membrane vesicles of obese rats.

Membrane vesicles from the small intestine brush border were obtained and used to determine the possible effects of genetic or nutritional obesity on L-alanine uptake. Membrane vesicles from Zucker fa/fa obese rats and cafeteria diet-fed Zucker Fa/? rats showed the same characteristics as those of standard diet-fed lean animals. All preparations showed sodium-dependent transport as the main pathway for L-alanine uptake within the substrate concentration range tested. The apparent substrate affinity constant (Km) values and the pattern of inhibition of Na(+)-dependent L-alanine uptake by other amino acids (L-leucine and L-glutamine), suggests that system B involved in the transport of dipolar amino acids (formerly named Neutral Brush Border System) participates in the Na(+)-dependent transport of L-alanine. The affinity constant (Km) for L-alanine was essentially the same for all the groups studied (in the range of 10 mM). However, there was a higher (P < 0.05) maximal capacity (Vmax) in preparations from diet-induced obese animals (cafeteria diet) than that of genetically obese rats. These results indicate that either nutritional or genetic obesity may modify the capacity but not the affinity of transport systems for L-alanine uptake in the brush border of rat small intestine.

In vitro glucose and 2-aminoisobutyric acid uptake by rat interscapular brown adipose tissue.

The dependence upon substrate and insulin concentrations, as well as on sodium and potassium concentrations in the medium of the uptake of glucose and 2-aminoisobutyric acid, was determined for fragments of brown and white adipose tissues incubated in vitro. Brown adipose tissue showed a high capacity for glucose uptake at high glucose concentrations, this uptake being dependent on both glucose and insulin concentration. White adipose tissue showed much more limited uptake capabilities. The presence of Na+ and K+ had little effect on the uptake. The uptake of 2-aminoisobutyric acid was similar in both adipose tissues, being enhanced by physiological levels of insulin and depressed by ouabain. This amino acid transport was dependent on Na+ and K+ concentrations, and the overall transporting capability was two to three orders of magnitude lower than that for glucose. It was concluded that amino acids could not play a significant role as bulk thermogenic substrates for brown adipose tissue, as their transporters lack the plasticity of response to high substrate and insulin concentrations which characterize brown adipose tissue uptake of glucose.

Effect of cold-temperature exposure and acclimation on amino acid pool changes and enzyme activities of rat brown adipose tissue.

The amino acid pool composition and its concentration ratios with respect to blood and plasma, as well as the activities of alanine, aspartate and branched chain amino acid transaminases, glutamine synthetase, adenylate deaminase and glutamate dehydrogenase have been studied in the interscapular brown adipose tissue of control, 12-h cold-exposed and 15-day cold-acclimated rats. Cold temperature affected the amino acid metabolism and pool composition more intensely after 15 days than after 12-h cold-exposure, even though the patterns of change were very similar in both groups. Cold temperatures induced a decrease in glutamine and an increase in glutamate concentration in the tissue. This probably increased the metabolism of branched chain amino acids and caused a decrease in adenylate deaminase activity. It also seemed to increase alanine utilization. We concluded that amino acid metabolism in brown adipose tissue is enhanced by cold temperature acclimation.

Effect of alanine on in vitro glucose utilization by rat interscapular brown adipose tissue.

The rates of either glucose or alanine incorporation into tissue and oxidation to CO2 were studied in rat interscapular brown adipose tissue in order to evaluate the mutual influence of both substrates on their uptake and utilization. Tissue fragments were incubated in vitro in the presence of 1-10 mM glucose and 0.3-1.5 mM alanine. The highest glucose oxidation rate was obtained with the lowest alanine concentrations tested. This suggests that alanine inhibits glucose utilization by this tissue at concentrations that are within the physiological plasmatic range. Glucose levels had little effect upon alanine oxidation, but glucose had a permissive effect on the utilization of alanine. On the basis of these results, it is postulated that this glucose conservation effect of alanine on brown adipose tissue can help to prevent glucose wastage in postprandrial situations.

In vitro alanine utilization by rat interscapular brown adipose tissue.

The in vitro oxidation to CO2 and tissue incorporation of alanine label by pieces of rat interscapular brown adipose tissue (IBAT) has been investigated. Insulin increased both uptake and oxidation of alanine, as well as the incorporation of alanine label into tissue. This effect only was observed in the presence of glucose in the incubation medium. Noradrenaline hampered alanine incorporation, not affecting its rate of oxidation. IBAT from 4-h cold-exposed rats showed a higher alanine utilization than that of controls; however, IBAT pieces from both 36-h starved and 30-day cold-exposed rats presented lower rates of alanine utilization. The main fate of alanine taken up by the IBAT pieces was its oxidation to CO2. Part of the label was also incorporated into the fatty acid fraction of lipids. The results obtained in this study agree with a possible role of alanine as alternative energetic substrate for IBAT.

Induction of acetylcholinesterase expression during apoptosis in various cell types.

Acetylcholinesterase (AChE) plays a key role in terminating neurotransmission at cholinergic synapses. AChE is also found in tissues devoid of cholinergic responses, indicating potential functions beyond neurotransmission. It has been suggested that AChE may participate in development, differentiation, and pathogenic processes such as Alzheimer's disease and tumorigenesis. We examined AChE expression in a number of cell lines upon induction of apoptosis by various stimuli. AChE is induced in all apoptotic cells examined as determined by cytochemical staining, immunological analysis, affinity chromatography purification, and molecular cloning. The AChE protein was found in the cytoplasm at the initiation of apoptosis and then in the nucleus or apoptotic bodies upon commitment to cell death. Sequence analysis revealed that AChE expressed in apoptotic cells is identical to the synapse type AChE. Pharmacological inhibitors of AChE prevented apoptosis. Furthermore, blocking the expression of AChE with antisense inhibited apoptosis. Therefore, our studies demonstrate that AChE is potentially a marker and a regulator of apoptosis.

Effect of arsenic trioxide on viability, proliferation, and apoptosis in human megakaryocytic leukemia cell lines.

Arsenic trioxide (As2O3) has been demonstrated to be effective for the treatment of acute promyelocytic leukemia (APL) and to inhibit proliferation and produce apoptosis in the APL cell line NB4. To determine if As2O3 might be useful for the treatment of other lineages, we investigated the effects of As2O3 on viability, proliferation, and induction of apoptosis in the megakaryocytic leukemia cell lines HEL, Meg-01, UT7, and M07e. Our results showed that As2O3, at concentrations of 0.1-2.0 microM, causes a dose- and time-dependent inhibition of survival and growth in all four megakaryocytic leukemia cell lines studied. In contrast, As2O3 at similar concentrations had no effects on either viability or growth of the nonmegakaryocytic leukemia cell line HL60 and two human breast cancer cell lines, ZR75 and MCF7. In situ end-labeling of DNA fragments (TUNEL assay) indicated that As2O3, at concentrations of 0.5-2 microM, could significantly induce apoptosis in the aforementioned four megakaryocytic leukemia cell lines, but not in the nonmegakaryocytic HL60, ZR75, and MCF7 cell lines. These results were confirmed using conventional morphologic assessment and the DNA ladder assay. Induction of apoptosis in arsenic-treated Meg-01 and UT7 cells was accompanied by a dose-response decrease of Bcl-2 protein, whereas As2O3 had no effect on this measurement in HL60, ZR75, and MCF7 cell lines. Pertinently, these concentrations of As2O3 produced identical changes in the characteristics of the APL cell line NB4. Collectively, these data demonstrate that As2O3 can selectively inhibit growth and induce apoptosis in megakaryocytic leukemia cell lines. The use of As2O3 for the treatment of malignant megakaryocytic disorders should be considered.

Plasma leptin turnover rates in lean and obese Zucker rats.

Conscious female adult lean and obese Zucker rats were injected through the jugular vein with radioactive iodine-labeled murine leptin; in the ensuing 8 min, four blood samples were sequentially extracted from the carotid artery. The samples were used in a modified RIA for leptin, in which paired tubes received the same amount of either labeled or unlabeled leptin, thus allowing us to estimate both leptin levels and specific radioactivity. The data were used to determine the decay curve parameters from which the half-life of leptin (5.46 +/- 0.23 min for lean rats and 6.99 +/- 0.75 min for obese rats) as well as the size of its circulating pool (32 pmol/kg for lean rats and 267 pmol/kg for obese rats) and the overall degradation rate (96 fkat/kg for lean rats and 645 fkat/kg for obese rats) were estimated. These values are consistent with the hormonal role of leptin and the need for speedy changes in its levels in response to metabolic challenge.

Rat insulin turnover in vivo.

Zucker lean and obese rats were injected under pentobarbital anesthesia with 125I-labeled insulin; at timed intervals from 30 to 120 sec, blood samples were extracted and used for the estimation of insulin levels by RIA. A group of rats from each series was maintained under a constant infusion of noradrenaline. For each insulin determination, a duplicate blood sample containing the same amount of insulin as that used in the RIA, but without the radioactive label, was used as a blank for insulin measurement. The radioactivity in these tubes was then used for the measurement of insulin label per ml blood. From plasma label decay curves and insulin concentrations, the insulin pool size, half-life, and rate of degradation were calculated. Obese rats had higher insulin levels (2.43 nM) and showed less effect of noradrenaline than their lean counterparts, in which insulin distribution volume shrank with noradrenaline treatment. The half-life of plasma insulin was similar in all groups (range, 226-314 sec). Pool size and overall degradation rates were higher in obese (198 femtokatals) than in lean rats (28 femtokatals). It is postulated that obese rats synthesize and cleave much more insulin than lean controls despite their higher circulating levels of insulin.

Insulin degradation by adipose tissue is increased in human obesity.

White adipose tissue samples from obese and lean patients were used for the estimation of insulin protease and insulin:glutathione transhydrogenase using 125I-labeled insulin. There was no activity detected in the absence of reduced glutathione, which indicates that insulin is cleaved in human adipose tissue through reduction of the disulfide bridge between the chains. Obese patients showed higher transhydrogenase activity (per U tissue protein wt, per U tissue wt, and in the total adipose tissue mass) than the lean group. There is a significant correlation between the activity per U tissue wt, and protein and total activity in the whole adipose tissue with respect to body mass index, with a higher activity in obese patients. The potential of insulin cleavage by adipose tissue in obese patients was a mean 5.6-fold higher than that in controls. The coexistence of high insulinemia and high cleavage capability implies that insulin secretion and turnover are increased in the obese. Thus, white adipose tissue may be crucial in the control of energy availability through modulation of insulin cleavage.

Is leptin an insulin counter-regulatory hormone?

Leptin, the product of the ob gene, controls appetite through the hypothalamus and may affect many other tissues because of the widespread distribution of its receptors. Leptin is synthesized by white adipose tissue (WAT) under conditions of high energy availability and insulin stimulus. Glucocorticoids enhance this synthesis and catecholamines hamper leptin production. Leptin diminishes insulin secretion by the pancreatic beta cells and induces insulin resistance. In fact leptin hampers insulin action on WAT itself in a negative feedback loop. The evidence acquired in studies on diabetics, starvation, refeeding and insulin and glucose clamps supports this interpretation, which may also explain part of the difficulties encountered by the current postulate that links leptin to WAT mass size signalling to the brain. Leptin may be, essentially, a counter-regulatory hormone limiting the insulin drive to store energy in the form of fat, its effects reaching from a decrease in food intake to lower insulin secretion and increased resistance to insulin and lower glucose uptake and fat synthesis by WAT.