Hypothalamic Monoaminergic Activity in 11-Week-Old Cold-Exposed Female Lean (Fa/Fa) and Obese (fa/fa) Zucker Rats

We previously reported that serotonergic activity was reduced in the ventromedial hypothalamic nucleus (VMN) of obese vs. lean male Zucker rats. To verify that this reduction was associated with genotype rather than gender, we measured monoamines and their major metabolites in hypothalamic nuclei of ll-week-old female lean (Fa/Fb) and obese (fa/fb) Zucker rats. In addition, since the thermic response to cold is reported to differ between lean and obese rats, some rats were also exposed to 9° or 22° C for 2h to determine if cold exposure altered hypothalamic monoaminergic activity. As in males, levels of 5-hydroxyindoleacetic acid [5-HIAA; major metabolite of serotonin (5-HT)] and the ratio of 5-HIANS-HT were lower in the VMN of obese vs. lean females (P = 0.008, 0.001, respectively). S-HIANS-HT was also reduced in the paraventricular (PVN) and suprachiasmatic nuclei (SCN) of the obese compared to the lean females. Cold exposure significantly stimulated brown fat mitochondria1 GDP binding in lean but not obese rats. Similarly, levels of norepinephrine, dopamine (DA), 5-HIAA, and 5-HT in the PVN, and 5-HIAA in the SCN increased in cold-exposed lean but not obese rats. In contrast, VMN and preoptic 3,4-dihydroxyphenylacetic acid (DOPAC; major metabolite of DA) increased in the cold-exposed obese but not lean animals. We conclude that: (1) the blunted peripheral response to cold in obese vs. lean Zucker rats is accompanied by altered hypothalamic monoaminergic activity, the physiological role of which needs further evaluation; and 2) depressed VMN serotonergic activity is associated with the obese genotype (fa/fa) rather than gender and as such may contribute to the reduced sympathetic and enhanced parasympathetic outflow from the VMN .     

Leptin Expression in Hypothalamic PVN Reverses Dietary Obesity and Hyperinsulinemia but Stimulates Ghrelin*

Objective: In order to circumvent the multiple peripheral effects of hyperleptinemia and leptin resistance, the efficacy of leptin transgene expression in the hypothalamic paraventricular nucleus (PVN) to reinstate the central energy homeostasis in obesity was examined. Research Methods and Procedures: A recombinant adeno‐associated viral vector encoding either leptin (rAAV‐lep) or green fluorescent protein (rAAV‐GFP) was microinjected into the PVN of obesity‐prone rats consuming a high‐fat diet (HFD). Results: rAAV‐lep, and not rAAV‐GFP, microinjection significantly reduced energy intake and enhanced energy expenditure, thereby resulting in normalization of weight and blood levels of leptin, insulin, free fatty acids, and glucose concomitant with enhanced ghrelin secretion during the extended period of observation. Discussion: Thus, we show, for the first time, that amelioration of leptin insufficiency with enhanced localized leptin availability in the PVN alone can reverse dietary obesity and the attendant hyperinsulinemia and concurrently block the central stimulatory effects of elevated endogenous ghrelin on food intake and adiposity.     

Enhanced Expressions of Arginine Vasopressin (Avp) in the Hypothalamic Paraventricular and Supraoptic Nuclei of Type 2 Diabetic Rats

Arginine vasopressin (AVP) is known to a neuropeptide that plays important roles in water conservation, sodium homeostasis, and in the regulation of serum osmolality. Several studies have reported that the elevated AVP level is related with diabetes mellitus as an acute or chronic stressor using type 1 diabetes mellitus animal models. However, it is unclear as to how the immunoreactivity and protein level of AVP in the brain is regulated in animal models of type 2 diabetes mellitus. In the present study, Zucker diabetic fatty (ZDF) rats were employed as a type 2 diabetes mellitus model and were compared with Zucker lean control (ZLC) rats with respect to AVP protein expression. Furthermore, in order to verify the regulation of AVP expression before and after the onset of diabetes mellitus, pre-diabetic rats (4 week-old) and obese-diabetic rats (12 week-old) were used. Blood glucose levels and water consumption were also measured and the results showed significantly high in 12 week-old ZDF than any other groups. AVP expression levels in the paraventricular nucleus and supraoptic nucleus were found to be significantly higher in 12 week-old ZDF rats than in 12 week-old ZLC rats and than in 4 week-old rats by immunostaining and western blotting. Enhanced expression of AVP in these animals may be associated with type 2 diabetes mellitus. Special issue article in honor of George Fink.     

下丘脑弓状核PYY对大鼠摄食、胃运动和能量代谢的影响及机制

目的:探究YY肽(PYY)对雄性Wistar大鼠的摄食、胃运动和能量代谢的影响及潜在机制。方法:采用免疫组织化学实验方法观察大鼠下丘脑弓状核(ARC)中Y2受体的表达;通过ARC微量注射PYY,观察其对下丘脑中编码摄食相关代谢激素的m RNA表达以及ARC中PYY反应性神经元的放电频率、食物摄入量及水摄入量、氧气消耗(VO_2)、CO_2产生(VCO_2)及能量代谢的影响。结果:免疫组化结果显示大鼠ARC内存在Y2受体;大鼠ARC注射PYY能够兴奋PYY反应性神经元,上调可卡因-苯丙胺调节转录肽(CART)及促肾上腺皮质释放激素(CRH)等抑食肽m RNA的表达,下调神经肽Y(NPY)及下丘脑泌素(HCRT)等促食肽m RNA的表达;且抑制大鼠食物摄入量,并参与调控大鼠呼吸、能量代谢及胃运动的改变。结论:ARC微量注射PYY可减少食物摄入并调节全身能量平衡,PYY可能是一种新型代谢肽。     

The Effect of Swelling on TRH and Oxytocin Secretion From Hypothalamic Structures

Summary 1. Cell swelling induces exocytosis of material stored in secretory vesicles resulting in a secretory burst of peptidic hormones or enzymes from various types of cells including endocrine cells and neurons. We have previously shown that swelling-induced exocytosis possesses limited selectivity; hypotonic medium evokes TRH but not oxytocin release from hypothalamic paraventricular nucleus (PVN) and neurohypophysis (NH).2. It is the aim of this study to ascertain whether the swelling-induced oxytocin secretion could be unmasked by the inhibition of specific osmotic response using Ca²⁺-free medium and GdCl₃, an inhibitor of stretch activated channels.3. Oxytocin release from the PVN was stimulated by the hypotonic medium only in the presence of 50 or 100 μM GdCl_3. Oxytocin release from supraoptic nucleus (SON) was also stimulated by the Ca²⁺-free hypotonic medium in the presence of GdCl₃. Oxytocin secretion from the NH was not stimulated even in the presence of GdCl₃, both in Ca²⁺ containing and Ca²⁺-free medium. TRH response to swelling-inducing stimulus was not affected by the presence of GdCl₃.4. An intranuclear oxytocin secretion to hyposmotic stimulation within the PVN and the SON could be unmasked by the inhibiting specific response by GdCl₃. At these conditions general secretory response to swelling-inducing stimuli emerged. Secretion of oxytocin from the NH was not affected by any of these treatments.5. Peptides and proteins released after cell swelling can play an important role in the pathophysiology of ischemia and could be mediators of local or remote preconditioning. Disruption of mechanosensitive gating in magnocellular neurosecretory cells could result in an inadequate secretory response (e.g. stimulation instead of inhibition and vice versa) of hormones engaged in water and salt metabolism regulation.     

Metabolic Response to a Mixed Meal in Obese and Lean Women from Two South African Populations

Objective: Lower lipid and insulin levels are found during a glucose-tolerance test in obese black than obese white South African women. Therefore, β-cell function and lipid metabolism were compared in these populations during a mixed meal. Research Methods and Procedures: Blood concentrations of glucose, free fatty acids (FFAs), insulin, lipograms, and in vivo FFA oxidation were determined at fasting and for 7 hours after oral administration of a mixed emulsion containing glucose-casein-sucrose-lipid and [1-¹³C] palmitic acid in 8 lean black women (LBW), 10 obese black women (OBW), 9 lean white women (LWW), and 10 obese white women (OWW). Subcutaneous and visceral fat mass was assessed by computerized tomography. Results: Visceral fat area was higher in OWW (152.7 ± 17.0 cm²) than OBW (80.0 ± 6.7 cm²; p < 0.01). In OBW, 30-minute insulin levels were higher (604.3 ± 117.6 pM) than OWW (311.0 ± 42.9 pM; p < 0.05). Total triglyceride was higher in OWW (706.7 ± 96.0 mM × 7 hours) than OBW (465.7 ± 48.2 mM × 7 hours; p < 0.05) and correlated with visceral fat area (β = 0.38, p = 0.05). Palmitate oxidation was higher in lean than obese women in both ethnic groups and correlated negatively with fat mass (β = −0.58, p < 0.005). Discussion: The higher 30-minute insulin response in OBW may reflect a higher insulinotropic effect of FFAs or glucose. The elevated triglyceride level of OWW may be due to their higher visceral fat mass and possibly reduced clearance by adipose tissue.     

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.     

Changes of Islet Size and Islet Size Distribution Resulting from Protein-Malnutrition in Lean (Fa/Fa) and Obese (fa/fa) Zucker Rats

TSE, ELIZABETH O, FRANCINE M GREGOIRE, BRIGITTE REUSENS, CLAUDE REMACLE, JOSEPH J HOET, PATRICIA R JOHNSON, JUDITH S STERN. Changes of islet size and islet size distribution resulting from protein malnutrition in lean (Fa/Fa) and obese (fa/fa) Zucker rats. Potential alterations in islet size and islet size distribution resulting from protein malnutrition were studied in lean (Fa/Fa) and obese (fa/fa) Zucker rats. The purpose was to investigate whether the distribution of enlarged islets in obese rats was altered by low-protein feeding. Four-week-old, male, lean and obese Zucker rats were fed either a diet containing 20% (w/w) protein (control diet) or a diet containing 5% (w/w) protein (low-protein diet) for 3 weeks. Pancreata were dissected at autopsy and immunostained for insulin. Islet size and distribution were determined by morphometric analysis. Body-weight gain, food intake, and serum insulin and glucose were also measured. After 3 weeks on the diets, serum insulin was significantly lower in both lean (-75%) and obese (-54%) rats fed low protein compared with that in controls. However, obese rats were still hyperinsulinemic compared with lean rats. Protein malnutrition resulted in a shift in distribution of islets to smaller size both in lean and in obese rats, with an increase in the population of small islets (100 μm²) and a decrease in the population of large islets (>20,000 μ;m²). In lean and obese rats fed low protein, β-cell weight was significantly lower, B cell volume fraction tended to decrease, and islet number per section area was significantly elevated when compared with controls. Taken together, these results show that protein deficiency alters the endocrine pancreas in both lean and obese Zucker rats. Although the decrease in islet size and the shift in distribution to smaller islets most likely contribute to the decrease in serum insulin concentration, these changes appear insufficient to normalize hyperinsulinemia in the obese Zucker rat.     

Quantitation of Vasopressin mRNA and Oxytocin mRNA in Hypothalamic Nuclei by Solution Hybridization Assays

Concentrations of vasopressin (VP) precursor and oxytocin (OT) precursor mRNA were measured in magnocellular cell groups of the rat hypothalamus by newly developed solution hybridization assays. The assays employed single-stranded 35S-labeled VP-specific and OT-specific DNA probes that were prepared by primer extension on recombinant M13 DNA templates. Solution hybridization assays were standardized by known amounts of cloned DNA. The detection limit was less than 1 pg DNA equivalent of the respective mRNA. In total RNA preparations of microdissected supraoptic nucleus (SON) mean (+/- SEM) basal levels of 1.37 +/- 0.18 pg VP mRNA and 1.95 +/- 0.14 pg OT mRNA were measured. RNA of the microdissected paraventricular nucleus (PVN) contained 0.35 +/- 0.02 pg VP mRNA and 1.77 +/- 0.15 pg OT mRNA. Elevation of plasma osmolality induced by drinking of 2% saline for 25 days resulted in a 1.85-fold increase in VP mRNA levels of the SON and a 1.6-fold increase in VP mRNA levels of the PVN. The solution hybridization assays are suitable tools to study the regulation of VP and OT mRNAs in magnocellular neurons of the brain.     

Differential Responsiveness of Obese (fa/fa) and Lean (Fa/Fa) Zucker Rats to Cytokine-Induced Anorexia

Pathophysiological and pharmacological concentrations of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) in the cerebrospinal fluid (CSF) induce anorexia in normal rats. Obesity in humans and rodents is associated with increased TNF-α messenger RNA and protein levels in various cell types. This suggests that obese individuals may have differential regulation of cytokine production and dissimilar responsiveness to cytokines. In the present study, we investigated the effects of the intracerebroventricular (ICV) microinfusion of TNF-α (50, 100, and 500 ng/rat), IL-1β (1.0, 4.0, and 8.0 ng), and TNF-α (100 ng) plus IL-1β (1.0 ng) on obese (fa/fa) and lean (Fa/Fa) Zucker rats. The results show that: TNF-α and IL-1β, and the concomitant administration of TNF-a and IL-ip decreased the short-term (4 hours), nighttime (12 hours), and total daily food intakes in obese and lean rats; IL-1β was more potent relative to TNF-α; obese rats showed greater responsiveness to IL-1β: 8.0 ng IL-1β, for example, decreased the 12-hour food intake by 52% in obese and 22% in lean rats. On the other hand, obese and lean rats did not exhibit a significantly different responsiveness to the anorexia induced by 50,100, or 500 ng TNF-α at the 4-hour period; and the concomitant ICV administration of TNF-α and IL-1β induced anorexia with additive (4-hour period) or synergistic (12-hour and 24-hour periods) effects in obese rats. The effect of TNF-α plus IL-1β in lean rats was greater than additive for the 12-hour and 24-hour periods. The difference in suppression of total daily food intake by TNF-α plus IL-1β in obese (-43%) versus lean (-23%) rats was significantly different (p<0.01). The results show that obese (fa/fa) and lean (Fa/Fa) Zucker rats have differential responsiveness to the ICV microinfusion of two different classes of cytokines.     

Lactate Production from Glucose and Response to Insulin in Perifused Adipocytes from Mesenteric and Epididymal Regions of Lean and Obese Rats

Lactate, an important metabolic substrate for peripheral tissues and the liver, is released in significant amounts from adipose tissue. Using a perifusion system, we measured lactate production from glucose and response to insulin in isolated mesenteric and epididymal adipocytes removed from fed or fasted male Wistar rats at two stages of growth and development: (a) lean rats (7 weeks to 9 weeks old, weighing ～250 g), and (b) fatter rats (6 months to 8 months old, weighing ～550 g). The results show that lactate production in perifused adipocytes is regulated by the prior nutritional state of the animals, by the adipose tissue region, and by the presence of insulin in the perifusate. In fat cells from lean rats, basal lactate production was significantly higher (p<0.05) in mesenteric cells when compared with epididymal cells, both in the fed state (7.8 nmol/10⁷ fat cells per minute vs. 2.9 nmol/10⁷ fat cells per minute) and after 2 days of fasting (13.6 nmol vs. 3.5 nmol). When the response to 1 mU/mL insulin was studied, however, the relative increase in lactate production produced by insulin was greater in the epididymal cells than in the mesenteric cells, in both the fed (194% vs. 91% over basal, respectively) and fasted (360% vs. 55% over basal, p<0.05) state. When larger epididymal adipocytes from fatter rats were compared with an equal number of smaller epididymal cells from leaner rats, the larger cells produced 4.99 nmol of lactate/10⁷ fat cells per minute, whereas the smaller cells produced 2.93 nmol (p=0.08). Large fat cells showed a small and nonsignificant response to insulin in either type of cell (epididymal vs. mesenteric) or nutritional state (fed vs. fasted). This study indicates that distinct regional differences exist in lactate production and response to insulin. Mesenteric adipose tissue, which drains directly into the portal vein and provides substrates to the liver, may be an important source of lactate for the hepatic processes of gluconeogenesis and glycogenesis.     

Increased Expression of Complement Component C3 in the Plasma of Obese Zucker fa and LA/N fef Rats Compared with Their Lean Counterparts

Objectives : The objectives of this study were to determine whether there are differences in the electrophoretic profiles of plasma proteins from lean and obese rats and to identify a protein that was found to be more abundant in the plasma of obese rats. Research Methods and Procedures : Plasma proteins from lean and obese Zucker fa and LA/N/fa^frats were separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The identity of a band that was differentially expressed was determined by amino acid sequencing and Western blot analysis. Results : A band migrating approximately the same distance as the 116 kDa molecular weight marker was more prominent in plasma from obese rats than in plasma of lean rats. Partial sequencing of the peptide revealed that 17 of the first 18 amino acids at the amino terminus were identical with the corresponding residues in the α-chain of complement component C3. Western blot analysis confirmed the identity of the peptide as complement component C3. Complement C3 activity was measured using a hemolytic assay to determine whether there was a corresponding increase in the biological activity of this component in the serum of obese rats. Serum from obese rats was found to have 1.8 times as much complement component C3 activity as serum from lean rats. Discussion : Elevated levels of complement C3 in genetically obese rats may be relevant because increased amounts of C3 could serve as a reservoir from which increased amounts of acylation stimulating protein, a cleavage product of complement C3, could be produced.     

Effect of Development of Habituation to Restraint Stress on Hypothalamic Noradrenaline Release and Adrenocorticotropin Secretion

Abstract: The effect of repeated stress has been studied on noradrenaline release in the hypothalamic paraventricular nucleus and on adrenocorticotropin levels. Rats were stressed by 20-min immobilization once a day for 5 days. On day 6 they were exposed to the same stress or to a different one (ether vapors for 2 min). Immobilization and ether stress increased noradrenaline release in naive rats (271 ± 43 and 197 ± 9%, respectively) and raised adrenocorticotropin levels, showing activation of the hypothalamus-pituitary axis. Repeated daily restraint did not modify basal noradrenaline or adrenocorticotropin levels. The further immobilization session on day 6 did not change noradrenaline levels at any observation time (20–120 min). The adrenocorticotropin response was still present, although significantly reduced. In repeatedly restrained rats, exposure to ether vapors induced a maximal increase in noradrenaline level similar to that observed in naive rats, although prolonged. In these rats the adrenocorticotropin response did not differ from that in acutely stressed rats. These results suggest that habituation may develop to a stressful stimulus leading to suppression of the hypothalamic noradrenergic response and that this phenomenon is stress specific. Moreover, modifications of noradrenaline release in the paraventricular nucleus are not solely responsible for the adrenocorticotropin response during stress, suggesting that other pathways and/or neurotransmitters are involved too.     

Effects of phenotype, sex, and diet on plasma lipids in LA/N-cp rats

The LA/N-corpulent (cp) rat is a recently developed congenic strain which exhibits obesity. The effects of phenotype and sex on serum and lipoprotein lipid content were examined in LA/N-cp rats fed either a control or an atherogenic diet high in saturated fat and protein. Obese rats were pair-fed to equivalent lean animals. Results from this study indicate that sex, phenotype, and diet exert significant effects on plasma and lipoprotein cholesterol content. Plasma cholesterol levels were higher in obese compared with lean rats, females than in males, and rats consuming the atherogenic diet compared with the control diet. Plasma and lipoprotein triglyceride levels were significantly increased only in obese compared with lean animals. The increased plasma cholesterol and triglyceride was observed primarily in the chylomicron and very low density lipoprotein fractions. Increased levels of plasma cholesterol were not a result of increased dietary cholesterol absorption or increased liver cholesterol biosynthesis. These data suggest that LA/N-cp rats can serve as a unique rodent model for the study of the interrelationships between hyperlipidemia, obesity, and coronary heart disease.     

下丘脑Orexin 对肥胖大鼠能量代谢的影响

目的:探讨下丘脑注射OXR-1选择性受体拮抗剂ACT-335827对肥胖大鼠代谢的效果。方法:通过高脂饮食建立肥胖大鼠模型,采用CODA 8通道高通量非侵入性血压系统(EMKA)测量血压;所有脂类都使用商品酶试剂盒和TOSHIBA-40FR全自动分析仪测量;空腹血糖采用葡萄糖氧化酶法;空腹胰岛素采用放射免疫法测定。肥胖大鼠出现代谢紊乱后,给予ACT-335827处理,检测大鼠体重、血压、脂肪、甘油三酯、总胆固醇、高密度脂蛋白、低密度脂蛋白、游离脂肪酸(NEFA)、瘦素、空腹血糖及空腹胰岛素等的变化。结果:与普通饮食组相比,经过10周高脂饮食,高脂饮食组大鼠体重显著升高(P0.05),给予ACT-335827处理后,普通大鼠的体重、血压、脂肪含量、脂代谢等均无明显变化;与高脂饮食和高脂饮食加生理盐水处理组大鼠比较,高脂饮食加ACT-335827处理组肥胖大鼠的体重显著下降(P0.05),腹部和附睾脂肪含量下降(P0.05),低密度脂蛋白、甘油三酯、总胆固醇、瘦素水平下降(P0.05),空腹血糖及空腹胰岛素也显著降低(P0.05),但血压、肠系膜脂肪和肩胛棕色脂肪、高密度脂蛋白和NEFA无明显变化(P0.05)。结论:ACT-335827对肥胖大鼠的代谢紊乱具有改善作用,对肥胖大鼠有一定的减肥作用。     

The effect of experimental overnutrition on nonshivering thermogenesis and obesity in LA/N-cp rats.

1. Groups of congenic adult male lean and obese LA/N-cp rats were fed stock chow or the chow diet plus a cafeteria diet supplement from 4 until 6 months of age. 2. Weight gain, adipose cellularity, and adiposity were greater in obese than in lean rats and all three parameters increased more rapidly in obese than in lean rats when fed the cafeteria-supplemented diet. 3. Resting metabolic rates and basal urinary vanilylmandelic acid excretion were greater in lean than in obese rats, while serum triiodothyronine concentrations were similar in both phenotypes. The cafeteria diet was associated with significant increases in all three metabolic parameters in lean but not in obese rats. 4. The results of this study indicate that the obese phenotype of this strain has an impaired capacity for non-shivering thermogenesis (NST), in association with an enhanced propensity for development of obesity when fed stock or cafeteria diets. Moreover, the impairment in NST involves both sympathetic and thyroidal components, and is likely to be contributory if not causative of obesity in this strain.     

Influence of Smoking on Hormone Secretion in Obese and Lean Female Smokers

Smoking exerts influences on the secretion of several hormones which are abnormal in obesity. Previous studies have mainly been performed in non-obese men, and data from non-obese and obese women are scarce. The aim of the present study was therefore to identify the effect of smoking on hormone secretions in obese and lean female smokers. The study was performed in 10 obese and 8 lean, premenopausal, healthy smokers. All subjects were tested once under experimental and once under control conditions (not smoking) in randomized order. The women smoked two non-filtered cigarettes during 4 minutes each. Blood pressure and heart rate were measured 30 minutes before smoking, at the start of smoking (time 0) and then after 5, 10, 20, 30, 45 and 60 minutes. Blood samples were taken for determination of serum concentrations of adrenocorticotropic hormone (ACTH), Cortisol, prolactin (PRL), growth hormone (GH) and thyroid stimulating hormone (TSH) at the same time points except at 5 minutes. Heart rate rose in both groups during smoking. Systolic and diastolic blood pressure was increased only in the obese subjects. Cortisol and ACTH increased in both groups, while TSH, PRL and GH were unchanged in both groups. We conclude that lean and obese smoking women seem to respond rather similarly to smoking in the hemodynamic and endocrine variables measured in this report with the possible exception of blood pressure where the obese women tended to show more pronounced increases.     

Corn Gluten Hydrolysate Affects the Time-Course of Metabolic Changes Through Appetite Control in High-Fat Diet-Induced Obese Rats

This study first investigated the effects of corn gluten hydrolysate (CGH) (1.5 g/day) administration for 7 days on appetite-responsive genes in lean Sprague-Dawley (SD) rats. In a second set of experiments, the metabolic changes occurring at multiple time points over 8 weeks in response to CGH (35.33% wt/wt) were observed in high-fat (HF, 60% of energy as fat) diet-fed SD rats. In lean rats, the hypothalamus neuropeptide-Y and proopiomelanocortin mRNA levels of the CGH group were significantly changed in response to CGH administration. In the second part of the study, CGH treatment was found to reduce body weight and perirenal and epididymal fat weight. CGH also prevented an increase in food intake at 2 weeks and lowered plasma leptin and insulin levels in comparison with the HF group. This reduction in the plasma and hepatic lipid levels was followed by improved insulin resistance, and the beneficial metabolic effects of CGH were also partly related to increases in plasma adiponectin levels. The Homeostasis Model of Assessment - Insulin Resistance (HOMA-IR), an index of insulin resistance, was markedly improved in the HF-CGH group compared with the HF group at 6 weeks. According to the microarray results, adipose tissue mRNA expression related to G-protein coupled receptor protein signaling pathway and sensory perception was significantly improved after 8 weeks of CGH administration. In conclusion, the present findings suggest that dietary CGH may be effective for improving hyperglycemia, dyslipidemia and insulin resistance in diet-induced obese rats as well as appetite control in lean rats.     

Effect of Destruction of the Suprachiasmic Hypothalamic Nuclei on Autosensitization in the Organism of Rats

Examination of the effects of destruction of the suprachiasmic hypothalamic nuclei in rats allowed us to study the interaction between the nervous, immune, and endocrine systems, as well the involvement of structures of the anterior hypothalamus in the neuroimmune interaction. After such an intervention, we measured the following immunological indices: the content of leukocytes in the peripheral blood, the level of circulating immune complexes, and the sensitization of immunocompetent cells to organism's own tissues (of a few CNS structures, thymus, spleen, kidneys, and heart). Our experiments prove the existence of significant interaction between the nervous, immune, and endocrine systems and support the concept of a noticeable involvement of the suprachiasmic nuclei in the control of tolerant relations between the immune system and cells of the organism's own tissues.     

The effects of norepinephrine and nutritional status on resting metabolic rates in the LA/N-cp rat

1. The effects of diet and norepinephrine (NE) on resting metabolic rate (RMR) were determined using indirect calorimetry in 6-month-old lean and corpulent LA/N-cp rats. RMRs of lean rats were greater than the corpulent. 2. Ingestion of carbohydrate (CHO) in the unfasted and fasted states increased the RMR of both groups, especially in the lean phenotype when compared to oil. 3. Serum T3 and glucose concentrations were similar in both phenotypes. 4. The effects of NE on RMR were maximal after a 200 micrograms NE/kg body weight injections.