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X Remesar

Publications and source records attributed to X Remesar.

At least 55 records · Page 3Linked to original sources
PubMed1999

Effect of food deprivation on rat plasma estrone fatty acid esters.

The present study was devised to determine whether the circulating levels of estrone fatty esters are modified by 6-48 h starvation in the rat, in parallel to changes in fat reserves, as a test to check the plausibility of its function as a ponderostat signal in the mammal. Food deprivation resulted in a decrease in glucose and triacylglycerols, rapid disappearance of liver glycogen and increases in fatty acids and, especially, 3-hydroxybutyrate. Insulin and leptin decreased, corticosterone and free estrone increased from 6 h onwards and total estrone levels were maintained. Starvation reduced the lipid content of the rat by 25.6%. Plasma esterified estrone levels decreased more slowly, by 13% in 48 h, but its circulating mass decreased in the same proportion as the total lipid content of the rat. The small change in circulating estrone fatty esters is consistent with the postulated role of oleoyl-estrone as a medium-term ponderostat signal.

3-Hydroxybutyric Acid↗
PubMed1999

Distribution of oleoyl-estrone in rat plasma lipoproteins.

Pooled adult normal rat plasma was used for the separation of lipoprotein fractions: VLDL, LDL and HDL, from which a total lipids extract was obtained. The presence of fragments with the MW of estrone and oleoyl-estrone in the lipoprotein fractions was analyzed by HPLC-MS. The results show that oleoyl-estrone is the major estrone component in lipoproteins; this molecular species was present in all three lipoprotein lipid extracts. The lipoprotein fractions were used for the analysis of protein and lipid classes: triacylglycerols, total and esterified cholesterol and phospholipids as well as acyl-estrone. About half of the total acyl-estrone was in the HDL fraction and only about 10% in the VLDL fraction. HDLs contained about one molecule in 50 particles, LDLs one molecule per particle and VLDLs 15 molecules per particle, i.e. given their size, the larger lipoproteins contained more oleoyl-estrone than the HDLs. The distribution of this hormone suggests that oleoyl-estrone is lost with other lipids as the lipoproteins shrink. The results presented show that oleoyl-estrone is a molecule found naturally in rat lipoproteins in low concentrations - the lowest in HDLs - that are consistent with its postulated role in the control of body weight.

Animals↗
PubMed1998

Differential short-term distribution of estrone and oleoyl-estrone administered in liposomes to lean and obese Zucker rats.

Thirteen-week-old female Zucker lean (Fa/Fa) and obese (fa/fa) rats were injected through a cannula inserted in the left jugular vein with 1 mL/kg of 3H-labeled oleoyl-estrone in liposomes (Merlin-2) (i.e., 670 fmol, 84 kBq). The rats were killed 10 minutes later and dissected. The presence of intact or hydrolyzed oleoyl-estrone was later determined in all samples. The pattern of distribution of estrone was quite different from that of oleoyl-estrone both in rats that were lean and in those that were obese. Estrone was better retained by white adipose tissue than oleoyl-estrone. Liver, spleen, and lungs accumulated more oleoyl-estrone and split part of it, from 4.7% (lung, obese) to 27% (liver, lean). The overall high retention of estrone by the rat tissues results in its very low circulating levels. The fast splitting of liposome-carried oleoyl-estrone by most tissues (up to more than 67% by intestine and skin of lean rats) may help explain the rise in blood free estrone. The differences between lean and obese Zucker rats are mainly quantitative in the case of estrone, the main differences being found in blood and adipose tissues. However, when we compare the data for oleoyl-estrone, the differences cannot be dismissed simply as due to differences in body size or the extent of fat deposits. A large portion of the label remained in the blood of the rats that were obese but not in those that were lean, the tissues of which took up more label. Brown adipose tissue shows a fair affinity for oleoyl-estrone in the rats that were lean but practically does not retain label in the rats that were obese, suggesting that oleoyl-estrone may have a direct effect on brown adipose tissue. The decreased uptake of oleoyl-estrone in rats that were obese shows that the mechanism regulating the turnover or disposal of this signal is altered in this type of genetic obesity.

Adipose Tissue↗
PubMed1998

Hind leg heat balance in obese Zucker rats during exercise.

To analyse the effect of obesity on exercise-derived heat dissipation, lean and obese Zucker rats were exercised on an inclined treadmill until they would no longer run with gentle prodding. We measured their oxygen consumption, water vapour loss, the concentrations of adenosine tri- and diphosphate, creatine phosphate, and lactate in quick-frozen leg muscles, and the temperature of muscle, skin and blood in the aorta. We determined blood flow to leg muscle, fat and skin by measuring the entrapment of fluorescent microspheres. From the measurements we calculated heat flow rates between hind leg muscle, blood, fat and skin and the environment. The obese rats weighed twice as much as the lean (340-400 g and 175-200 g respectively) and ran half as fast (113 +/- 7 m versus 257 +/- 17 m). The differences between the two groups for basal oxygen consumption (lean: 6.7 +/- 0.9 micromol/min, obese: 5.0 +/- 1.9 micromol/min) and exercising oxygen consumption (lean: 37.8 +/- 5.6 micromol/min, obese: 22.2 +/- 3.8 micromol/min) were not significant. Both groups stopped running after the same time at their maximal speed (lean: 4.5 +/- 0.3 min, obese: 4.2 +/- 0.2 min). During exercise, lean rats had higher increases in core temperature (lean: 0.7 degrees C, obese: 0.4 degrees C) and muscle temperatures (lean: 1.3 degrees C, obese: 0.7 degrees C) than the obese rats. The calculated heat flows indicated a predominant conductive transfer of heat from muscle through the skin in lean rats but a higher proportion of heat transfer to the blood in obese rats. It is concluded that muscle heat accumulation did not cause fatigue in either case.

Animals↗
PubMed1998

During intense exercise, obese women rely more than lean women on aerobic energy.

A series of untrained, healthy, obese women (body mass index 32.5 +/- 0.9 kg.m-2) were subjected to a protocol of intense exercise on a cycloergometer and compared with lean controls (body mass index 20. 9 +/- 0.5 kg.m-2). Physiological parameters, blood lactate, bicarbonate, plasma metabolites, oxygen consumption and CO2 production were measured. Impedance-derived extracellular water and plasma changes in lactate and bicarbonate were used to determine changes in bicarbonate pools and lactate-displaced CO2. From these and respiratory gases, the respiratory quotient was calculated and thence overall fuel consumption. Anaerobic energy during exercise accounted for about 1.8% of all energy consumed in the lean but only 0.7% in the obese. Obese women fatigued at lower workloads and energy expenditure levels than did the lean, and their lactate buildup was similar when compared on the basis of fat-free mass. The data support the postulation of fatigue being triggered by a combination of factors: stretched cardiovascular work would be the main factor for obese women, in part limiting lactate production. For lean women, the triggering factor for fatigue could be the loss of buffering capacity; but it is the combination of stretching cardiovascular capacity, exhaustion of glycogen and available glucose and increase in lactate/loss of bicarbonate buffer that determines the onset of fatigue.

Adult↗
PubMed1998

Structural determinants of oleoyl-estrone slimming effects.

Female adult 9-week old Wistar rats were implanted with osmotic minipumps releasing for 14 days a liposome suspension (controls) loaded with oleoyl-estrone or other compounds of the Merlin series: estrone, estradiol, oleoyl-estradiol, oleoyl-DHEA, stearoyl-estrone, palmitoyl-estrone, oleoyl-diethylstilbestrol (DES), estrone oleoyl-ether and oleoyl-3-methoxy-estrone. All compounds were given at the same dose of 3.5 micromol/day x kg for 14 days. The effects on body weight and food intake were recorded. In the case of estrone esters, the body composition and nitrogen balance were also determined. The chronic administration of oleoyl-estrone in liposomes to rats lowers food intake, maintaining energy consumption, thus inducing the active utilization of internal stores and, consequently, the loss of body weight. This loss is mainly due to a decrease in fat, with lower proportional losses of water and a limited consumption of body protein. Free estrone had no effects on body weight, but estradiol did induce a decrease in body weight, similar to that of oleoyl-estradiol. Oleoyl-DHEA had no significant effect on body weight nor in food intake. Oleoyl-DES mimicked fairly well the effects of oleoyl-estrone, both affecting food intake and body weight. There was a relative lack of effects of estrone oleoyl-ether and of oleoyl-3-methoxy-estrone. The effects of oleoyl-estrone were in part mimicked by stearoyl- and palmitoyl-estrone, but their activity on a molar basis was lower, which suggests that the fatty acid moiety significantly influences the activity of the estrone ester as a slimming agent. The differences observed in the appetite suppression and overall slimming power of the stearoyl and palmitoyl-estrone clearly indicate that the sites of action of the physiological agonist oleoyl-estrone are at least two; the shape of the molecule, thus, may elicit a different degree of response of the systems controlled by oleoyl-estrone levels. From this interaction a series of global effects are elicited, such as appetite suppression and the loss of body (fat) weight, the latter in part (but not only) due to decreased food intake. The results shown here also suggest that the overall configuration of fatty acyl-estrone is more constrictive for its function as slimming agent than for its role as appetite suppressant, which hints to different target organs or sites of action endowed with receptors showing different degrees of fulfilling the structural constrictions of the agonist molecule.

Animals↗
PubMed1998

Formaldehyde derived from dietary aspartame binds to tissue components in vivo.

Adult male rats were given an oral dose of 10 mg/kg aspartame 14C-labelled in the methanol carbon. At timed intervals of up to 6 hours, the radioactivity in plasma and several organs was investigated. Most of the radioactivity found (>98% in plasma, >75% in liver) was bound to protein. Label present in liver, plasma and kidney was in the range of 1-2% of total radioactivity administered per g or mL, changing little with time. Other organs (brown and white adipose tissues, muscle, brain, cornea and retina) contained levels of label in the range of 1/12 to 1/10th of that of liver. In all, the rat retained, 6 hours after administration about 5% of the label, half of it in the liver. The specific radioactivity of tissue protein, RNA and DNA was quite uniform. The protein label was concentrated in amino acids, different from methionine, and largely coincident with the result of protein exposure to labelled formaldehyde. DNA radioactivity was essentially in a single different adduct base, different from the normal bases present in DNA. The nature of the tissue label accumulated was, thus, a direct consequence of formaldehyde binding to tissue structures. The administration of labelled aspartame to a group of cirrhotic rats resulted in comparable label retention by tissue components, which suggests that liver function (or its defect) has little effect on formaldehyde formation from aspartame and binding to biological components. The chronic treatment of a series of rats with 200 mg/kg of non-labelled aspartame during 10 days resulted in the accumulation of even more label when given the radioactive bolus, suggesting that the amount of formaldehyde adducts coming from aspartame in tissue proteins and nucleic acids may be cumulative. It is concluded that aspartame consumption may constitute a hazard because of its contribution to the formation of formaldehyde adducts.

Administration, Oral↗
PubMed1998

Oleoyl-estrone does not alter hypothalamic neuropeptide Y in Zucker lean and obese rats.

Female Zucker lean and obese rats were treated for 14 days with 3.5 micromol/kg oleoyl-estrone (OE) in liposomes (Merlin-2). After 0, 3, 6, 10, and 14 days of treatment, the rats were killed and hypothalamic nuclei (lateral preoptic, median preoptic, paraventricular, ventromedial and arcuate) were used for neuropeptide Y (NPY) radioimmunoassay. In 14 days, OE decreased food intake by 26% in lean and 38% in obese rats and energy expenditure by 6% in lean and 47% in obese rats; the body weight gap between controls and treated rats becoming -17.8% of initial b.wt. in the lean and -13.6% in the obese rats. Obese rats showed higher NPY levels in all the nuclei than the lean rats. Despite a negative energy balance and decreased food intake, there were practically no changes in NPY with OE treatment. The results indicate that oleoyl-estrone does not act through NPY in its control of either food intake or thermogenesis in lean and genetically obese rats.

Animals↗
PubMed1998

Zucker obese rats are insensitive to the CRH-increasing effect of oleoyl-estrone.

Adult female Zucker lean and obese rats were treated for 14 days with 3.5 nm/kg oleoyl-estrone (OE) in liposomes (Merlin-2) through continuous i.v. injection with osmotic minipumps. Rat wt. and food intake were measured daily. On days 0, 3, 6, 10, and 14, groups of rats were killed and their hypothalamic nuclei [lateral preoptic (LPO), median preoptic (MPO), paraventricular (PVN), ventromedial (VMH), and arcuate (ARC)] were dissected, homogenized, and used for the measurement of corticosterone-releasing hormone (CRH) by radioimmunoassay. The OE treatment decreased food intake by 67.4% in lean and 62.6% in obese rats (means for 14 days). Body wt. decreased steadily in lean and obese rats, the gap between controls and treated rats becoming 11.5% of initial body wt. in the lean and 12.4% in the obese. The levels of CRH in the ARC nucleus were at least 10-fold higher than in the other nuclei. No changes in CRH were observed in any of the nuclei of obese rats, with levels up to day 6 similar to those of lean rats. In the lean rats, the LPO and ARC nuclei showed peaks on day 10, while the MPO showed no changes and the PVN and VMH nuclei showed a progressive increase, to a maximum at the end of the study (day 14). This contrasted with the peak of plasma adrenocorticotropic hormone (ACTH) and corticosterone (day 6 in lean and day 14 in obese rats). There was a definite lack of correlation between the plasma levels of these two hormones and the levels of CRH in the hypothalamic nuclei, and between the latter and the decreases in appetite in the rats. The loss of appetite induced by OE is not necessarily mediated by CRH, because the obese rats show an intense decrease in voluntary food intake but their hypothalamic nuclei CRH levels do not change at all. Hypothalamic nuclei CRH does not, necessarily, mediate the rise in glucocorticoids induced by OE treatment, because this is observed in lean and obese rats, lean rats increases being mismatched with those of hypothalamic CRH. The OE induced changes in hypothalamic CRH require a fully functional leptinergic pathway, because it is not observed in Zucker fa/fa rats lacking a working leptin receptor. This--indirectly--shows that leptin is needed for its synthesis or modulation.

Adrenocorticotropic Hormone↗
PubMed1998

Effect of oleoyl-estrone administration on corticosterone binding to tissues of lean and obese Zucker rats.

A group of female Zucker lean and obese rats was treated with 3.5 micromol/day kg of oleoyl-estrone in liposomes (OE) injected i.v. continuously for 14 days with inserted osmotic minipumps. Samples of liver were extracted on days 0, 3, 6, 10 and 14 and the expression of corticosterone-binding globulin (CBG) was determined by Northern blot. On the same dates, the total binding capacity of plasma, liver, periovaric white adipose tissue (WAT) and subcutaneous WAT was also determined using tritium-labelled corticosterone. Treatment with OE resulted in diminished CBG gene expression in the liver, this being more marked in the obese rats. Basal (time 0) corticosterone binding was higher in the plasma, liver and WAT of lean rats. Treatment with OE resulted in a gradual and general loss of binding capacity in the plasma and all tissues studied, for lean and obese rats alike. Since CBG decreases may result in enhanced glucocorticoid availability (and effects), the global decrease in corticosterone binding observed can be interpreted as a counteractive response to the energy imbalance elicited by OE.

Adipose Tissue↗
PubMed1998

3-Hydroxybutyrate inhibits noradrenaline-induced thermogenesis in lean but not in obese Zucker rats.

OBJECTIVE: To determine the effect of 3-hydroxybutyrate (3OHB) on the thermogenic response to noradrenaline (NA) in lean and genetically obese Zucker fa/fa rats. DESIGN: Rats were infused with 18.7 nmol x kg(-1) x min(-1) of NA, supplemented, for 15 min, with 66.7 micromol x kg(-1) x min(-1) of R-3-hydroxybutyrate (3OHB). SUBJECTS: Pentobarbital-anaesthetized lean and obese Zucker rats. MEASUREMENTS: Aortic and interscapular brown adipose tissue (BAT) temperature; plasma NA, 3OHB, glucose and insulin levels during infusion. RESULTS: The NA-induced increase in aortic and BAT temperature was more marked in lean than in obese rats. In lean rats, the rise was arrested by 3OHB; but in obese rats 3OHB had no effect. Infusion of saline, glucose or 3OHB in the absence of NA did not induce changes in either temperature. NA infusion resulted in a rapid increase in plasma NA to 45-50 nM in both groups; this plateau was maintained for up to 60 min. The presence of 3OHB decreased the plasma NA of lean rats, but did not affect the plasma NA of the obese rats. Blood 3OHB rose to 1.2 mM during 3OHB infusion in both groups, and decreased on cessation of infusion. Blood glucose levels increased with NA infusion in both groups; the presence of high 3OHB levels decreased glucose levels only in lean rats. CONCLUSION: The changes in NA levels induced by 3OHB may help explain the effects observed on temperature and glucose. The defective thermogenic system of obese rats cannot be modulated by 3OHB, unlike thermogenesis in lean rats, on which 3OHB has a marked effect.

3-Hydroxybutyric Acid↗
PubMed1998

Effect of adrenalectomy on the slimming activity of liposome-carried oleoyl-estrone in the rat.

OBJECTIVE: To determine the extent of glucocorticoid counter-regulatory control in the slimming action of oleoylestrone. DESIGN: Control and adrenalectomized rats were subjected to a seven-day treatment with 3.5 micromol/kg/d oleoylestrone in liposomes injected i.v. continuously by implanted osmotic minipumps. SUBJECTS: Sham-operated control and adrenalectomized lean Zucker rats. MEASUREMENTS: Body weight and food intake; plasma glucose, urea, insulin, leptin and corticosterone; liver glycogen. RESULTS: Treatment with oleoyl-estrone resulted in decreases in body weight and in food intake, as well as in circulating glucose, insulin and leptin. Combined adrenalectomy and oleoyl-estrone treatment resulted in a loss of almost 15% body weight in only seven days, with a severe drop in circulating glucose and insulin, almost total disappearance of plasma leptin and liver glycogen and a 3-fold rise in circulating urea. Food intake decreased sharply, which resulted in the exhaustion of energy reserves. CONCLUSION: The results presented here, strongly support the hypothesis that glucocorticoids play an important role in the modulation of oleoyl-estrone-induced imbalance of energy intake and expenditure. The large effect of oleoyl-estrone on glucose, glycogen- and protein-derived (urea levels) energy in adrenalectomized rats, provides more evidence for the assumed protective role of glucocorticoids against the oleoyl-estrone-induced net loss of energy reserves. The results also show the powerful destabilizing effects of unchecked oleoyl-estrone on energy balance.

Adrenalectomy↗
PubMed1998

Increased leptin production in vivo and insulin cleavage by the omental adipose tissue of morbidly obese patients.

OBJECTIVE: The aim of this investigation was to assess the insulin cleavage capacity in obese humans. Increased insulin degradation by visceral adipose tissue has previously been demonstrated in obese rats and could be interpreted as a physiological response to hyperinsulinaemia. The recent characterization of leptin receptors in pancreatic beta cells, liver and muscle suggests that leptin may influence insulin function and metabolism. Our study focuses on the possible relationship between leptin secretion and adipose tissue insulin-degrading capacity. DESIGN AND PATIENTS: Insulin and leptin were measured in arterial blood and in the epiploic vein of morbidly obese (n = 7) and non-obese patients (n = 7) who were undergoing abdominal surgery. Arteriovenous insulin difference (AV insulin) was considered an in vivo marker of insulin degradation by the omental fat tissue. Statistical comparison between venous and arterial leptin was used to assess endogenous leptin production. MEASUREMENTS: Insulin was measured using an oligoclonal IRMA and leptin levels were determined by using a specific radioimmunoassay. RESULTS: Morbidly obese patients were hyperinsulinaemic compared to non-obese patients according to arterial insulin levels (P = 0.049) but not to venous levels. Insulin cleavage capacity, nil in the control group, was clearly significant in the morbidly obese patients (P = 0.001). In the morbidly obese group, leptin levels in venous epiploic samples were significantly higher (P = 0.028) than in the arterial samples, confirming in situ the synthesis of leptin by human white adipose tissue. We also observed a correlation between insulin arterial levels and venous leptin concentrations (P = 0.009) which supports the chronic leptinogenic effect of insulin suggested in previous works. Finally, our results show that venous leptin levels are correlated with the extent of insulin cleavage by omental tissue (P = 0.033). CONCLUSIONS: Morbidly obese patients have a higher white adipose tissue insulin cleavage capacity, which could partially diminish hyperinsulinaemia-derived adverse effects. High leptin production, a consequence of high insulin levels, may act as a signal to the insulin-degrading tissues in order to lower insulinaemia.

Adipose Tissue↗
PubMed1998

Corticosterone binding to tissues of adrenalectomized lean and obese Zucker rats.

The binding of corticosterone, dexamethasone and aldosterone was investigated in plasma and in homogenates of liver, kidney, brain, brown adipose tissue and visceral (periovaric) and subcutaneous white adipose tissues of Zucker lean and obese rats: intact controls, adrenalectomized and sham-operated. Corticosterone-binding globulin (CBG) accounted for most of the binding, whereas that of glucocorticoid and mineralocorticoid receptors was much lower. Plasma corticosterone levels increased in sham-operated and obviously decreased in the adrenalectomized animals. Sham-operated and adrenalectomized lean rats showed decreased plasma CBG; in the obese, CBG levels were lower than in controls and were not affected by either surgery. No variation with obesity or surgery was observed either in dexamethasone or aldosterone binding, the latter being practically zero in most samples. When expressed per unit of tissue protein, CBG activity was maximal in adipose tissues, with lowest values in brain and liver. In lean rats, tissue CBG activity decreased with either surgical treatment; no changes were observed in the obese, which also had lower CBG tissue levels. The relative lack of changes in CBG of obese rats suggests that they have lost -- at least in part -- the ability to counter-modulate the changes in glucocorticoid levels through CBG modulation, thus relying only on the control of corticosterone levels. This interpretation agrees with the postulated role of CBG modulating the availability of glucocorticoids to target cells.

Adipose Tissue↗
PubMed1998

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.

Animals↗
PubMed1997

Short-term treatment with oleoyl-oestrone in liposomes (Merlin-2) strongly reduces the expression of the ob gene in young rats.

Young female rats of 160-180 g were implanted with osmotic minipumps releasing 3.0 micromol/day per kg of oleoyl-oestrone in liposomes (Merlin-2) into the bloodstream for up to 14 days. Merlin-2 induced a loss of appetite in the first days, later recovered, and a decrease in body weight of 7%, which contrasts with the 15% increase in controls during the 2-week period. Neither plasma glucose nor urea was affected by treatment, but liver glycogen increased by 50% in 14 days. Insulin decreased slightly with Merlin-2 treatment. Plasma corticotropin (ACTH) and corticosterone showed a transient increase by day 6 of treatment. The expression of the ob gene in adipose tissue fell during the period studied to practically nil on day 14; circulating leptin levels decreased more than 70% from day 1 to day 14. Oestrone levels increased from 0.3 nM (controls) to a maintained 40-60 nM level for the rest of the experiment. Oleoyl-oestrone levels first increased 4-fold, to decrease again to the initial levels on day 10, increasing later to 100-fold on day 14. The three phases observed in food intake, weight loss and oleoyl-oestrone levels match fairly well, which supports the direct involvement of oleoyl-oestrone in body-weight control. However, the control of oleoyl-oestrone levels seems to be mediated in part by corticosterone. The practical disappearance of leptin synthesis coincides with the massive accumulation of oleoyl-oestrone in plasma. The results presented suggest the involvement of oleoyl-oestrone in the main mechanisms of control of body weight and its regulation by glucocorticoids and leptin.

Adipose Tissue↗
PubMed1997

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.

Adipose Tissue↗