Energy restriction with high-fat diet enriched with coconut oil gives higher UCP1 and lower white fat in rats

OBJECTIVE: To investigate the effects of overfeeding on a high fat diet, enriched in coconut oil, and the influence of food restriction on the uncoupling protein (UCP1) expression and on body fat content. DESIGN AND SUBJECTS: In experiment I, female Wistar rats were fed ad libitum either a normal-fat diet (control group, C) or a high-fat diet (HF), enriched in coconut oil, for 7 weeks. In experiment II, HF rats after finishing experiment I were fed (for 3 weeks) either the normal-fat diet (group CAHF, Control After High Fat) or food restricted diets which provided 60% of the energy intake of group CAHF: a group fed a low-energy, normal-fat diet (LENF) and another fed a low-energy, high-fat diet (LEHF). MEASUREMENTS: Body and fatty depot weights. Food intake. Protein and UCP1 levels of interscapular brown adipose tissue. RESULTS: High-fat diet feeding promoted an increase in body fat content, body weight and UCP1 levels. Energy restriction induced similar body weight reduction in groups LENF and LEHF. However, some adipose depots were more strongly reduced in the rats fed the high-fat diet enriched in coconut oil (group LEHF) than in the rats fed the normal-fat diet (Group LENF). Specific UCP1 was 2.0 (group LENF) and 3.4 (group LEHF) times higher than in controls (group CAHF). CONCLUSION: The coconut-oil enriched diet is effective in stimulating UCP1 expression during ad libitum feeding and in preventing its down regulation during food restriction, and this goes hand in hand with a decrease of the white fat stores.     

Long-term regulation of leptin expression is correlated with adipocyte number in obese rats

OBJECTIVE: To investigate long-term regulation of leptin expression in adipose tissues of obese JCR:LA-corpulent rats, which have been shown to overexpress leptin. DESIGN: Manipulation of adipose tissue growth in obese rats by dietary restriction. INTERVENTIONS: Weanling female obese rats were maintained on 1 of 3 diets until 8 months old. One group was allowed to feed ad libitum, the second was pair-fed with lean rats, and the third had food intake restricted to maintain weights equal to those of age-matched lean rats. OUTCOME MEASURES: Body and fat pad weights, leptin messenger RNA (mRNA) levels, and size and number of adipocytes in retroperitoneal fat pads. RESULTS: Adipose tissue mass was increased 6-fold in the obese rats compared with the lean ones, despite equal body weight and intake restriction that was sufficient to impair growth. Although leptin mRNA level was down-regulated by intake restriction, it was still twice as elevated in the obese rats as in the lean ones, and was highly correlated with specific fat pad mass and adipocyte number, but not with size. CONCLUSIONS: These data suggest that leptin expression is correlated with adipocyte number within a fat pad, and that there is inappropriate hepatic de novo synthesis and storage of triacylglycerols in obese rats. A role for leptin in nutrient partitioning is proposed.     

Midclavicular catheters in the antepartum population. A continuous quality improvement review

The obese gene (OB) product, leptin, has been shown to exert control on metabolic processes such as food intake and body weight homeostasis, possibly through a neuropeptide Y (NPY) neurotransmission. More recently, leptin has been shown to control several neuroendocrine axes, modulating pituitary hormone secretions in function of metabolic conditions. Since in the rat growth hormone (GH) secretion is dependent upon prevailing metabolic conditions, and NPY has been shown to be implicated in the feedback mechanisms of this hormone, we reasoned that leptin could also exert control over GH secretion and we examined this hypothesis in male rats submitted to a 3-day fast. Circulating leptin concentrations measured by RIA abruptly fell to low values after 24 h of fasting and remained low thereafter. Upon refeeding, leptin secretion regularly increased. As shown by others, pulsatile GH secretion had disappeared after 3 days of fasting. Centrally administered leptin (10 microg/day, i.c.v. infusion initiated at the beginning of the fasting period) totally prevented the disappearance of pulsatile GH secretion. No leak of centrally administered leptin to the general circulation was observed. Infusing the same amount of leptin intracerebroventricularly to rats receiving ad libitum feeding produced a severe reduction in food intake but maintained a normal GH secretory pattern. In contrast, pair-fed rats, submitted to the same food restriction, exhibited a marked reduction in GH secretion. Hypothalamic NPY gene expression, estimated by Northern blot analysis, was significantly increased in fasting rats, and decreased in leptin-treated, fasting rats. In rats receiving ad libitum feeding, leptin treatment reduced NPY gene expression, consistent with the observed reduction in food intake, whereas pair-fed animals logically exhibited increased NPY gene expression. In both situations with reduced feeding, normal GH secretion was seen in leptin-treated animals exhibiting low NPY gene expression, whereas decreased or abolished GH secretion was seen in animals not receiving leptin and exhibiting increased NPY mRNA levels. Interestingly, despite maintenance of normal GH secretion in leptin-treated, fasting rats, plasma IGF-I levels were low, as in vehicle-treated rats. Indeed, hepatic gene expression for both GH receptor and IGF-I was markedly reduced by fasting, and no correction was seen with leptin treatment. In summary, the regulation of GH secretion, at least the changes linked with malnutrition, appears to be dependent upon a leptin signal, perceived centrally, possibly related to circulating levels of this new hormone. The present data suggest that leptin can rescue normal pulsatile GH secretion by preventing the documented inhibitory action of NPY on GH secretion.     

Induction of uncoupling protein expression in brown and white adipose tissue by leptin

Deposition of excess body fat occurs when energy intake chronically exceeds energy expenditure. In ob/ob mice, the absence of leptin affects both components of the energy balance equation, and the mice become morbidly obese after weaning. Treatment of ob/ob mice with exogenous leptin reduces body weight by decreasing food intake and stimulating energy utilization, but even when saline- and leptin-injected ob/ob mice are pair-fed, mice receiving leptin lose significantly more weight. Therefore, the purpose of the present study was to test the hypotheses that uncoupling protein-1 (UCP1) expression is reduced in adipose tissue from ob/ob mice and is restored by treatment with exogenous leptin. Lean and ob/ob mice (5-6 weeks old) were housed at 23 C and treated with leptin (20 microg/g BW x day) for 3 days before they were killed. Compared with levels in lean littermates, UCP1 messenger RNA (mRNA) and protein levels were lower in brown adipose tissue (BAT) and retroperitoneal white adipose tissue (WAT) from ob/ob mice. Treatment of ob/ob mice with leptin reduced body weight and produced a 4- to 5-fold increase in UCP1 mRNA levels in both interscapular BAT and retroperitoneal WAT. The increases in UCP1 mRNA were accompanied by comparable increases in UCP1 protein in mitochondrial preparations from each tissue. Given that the sole known function of UCP1 is to uncouple oxidative phosphorylation, the present results are consistent with the conclusion that leptin stimulates energy utilization in ob/ob mice by increasing thermogenic activity and capacity (UCP1). In addition, the present results suggest that decreased UCP1 expression in BAT and WAT of ob/ob mice is in part responsible for their increased metabolic efficiency and propensity to become obese.     

Dietary fat type and energy restriction interactively influence plasma leptin concentration in rats

To investigate whether dietary fat source and energy restriction interactively influence plasma leptin levels and its association of leptin with insulin action, rats were fed diets containing either fish, safflower oil, or beef tallow (20% wt/wt) for 10 weeks. Groups of rats consumed each diet ad libitum or at 85% or 70% of ad libitum energy intake in a design that held fat intake constant. Graded levels of energy restriction caused body weight to decrease (P < 0.001) differently according to the dietary fat provided. Plasma leptin concentrations were 60% higher (P < 0.05) in the groups fed fish oil and safflower oil ad libitum compared with those in the beef tallow group, despite smaller perirenal fat mass and fat cell size in the fish oil-fed animals. Energy restriction resulted in a 62% decrease (P < 0.05) in leptin levels in fish oil- and safflower oil-fed rats, whereas no changes were observed in beef tallow-fed animals. Plasma insulin levels were lower (P < 0.05) in the fish oil group fed ad libitum compared with those in the two other diet groups. These data demonstrate a hyperleptinemic effect in animals consuming diets rich in polyunsaturated fatty acid, which can be normalized to the level of saturated fat consumption by mild energy restriction. Thus, dietary fatty acid composition, independent of adipose tissue mass, is an important determinant of circulating leptin level in diet-induced obesity.     

Lactation suppresses diurnal rhythm of serum leptin

Rats consume most of their daily food intake at night; serum leptin levels and adipose tissue leptin mRNA content are elevated at night in non-lactating rats fed ad libitum. Lactation induces massive hyperphagia with most food still consumed at night, but the nocturnal increase in leptin secretion was not observed in lactating rats. Thus the link between nocturnal food intake and increased serum leptin is broken during lactation and the hypoleptinaemia may be an important factor promoting the hyperphagia of lactation.     

Leptin and corticosterone have opposite effects on food intake and the expression of UCP1 mRNA in brown adipose tissue of lep(ob)/lep(ob) mice

The present study was conducted to assess the interaction effect of leptin and corticosterone on food intake and the expression of uncoupling protein 1 (UCP1) mRNA in interscapular brown adipose tissue (IBAT). To this end, a 3 x 3 factorial experiment was designed in which adrenalectomized (ADX) lep(ob)/lep(ob) mice were subjected to three doses of corticosterone and three doses of leptin. The results confirm the anorectic and orexigenic effects of leptin and corticosterone, respectively. The results also emphasize the abilities of leptin and corticosterone to respectively increase and reduce the expression of UCP1 mRNA in IBAT. The effects of leptin and corticosterone on food intake and the expression of UCP1 mRNA translated into effects on body weight and body composition; leptin reduced body weight and corticosterone increased the weight of IBAT. The present results do not provide evidence for leptin-corticosterone interactions in the control of food intake and thermogenesis. Corticosterone increased food intake and reduced the expression of IBAT UCP1 regardless of the leptin status, and leptin reduced food intake and induced the expression of IBAT UCP1 independently of the corticosterone levels.     

Leptin selectively decreases visceral adiposity and enhances insulin action

Intraabdominal adiposity and insulin resistance are risk factors for diabetes mellitus, dyslipidemia, arteriosclerosis, and mortality. Leptin, a fat-derived protein encoded by the ob gene, has been postulated to be a sensor of energy storage in adipose tissue capable of mediating a feedback signal to sites involved in the regulation of energy homeostasis. Here, we provide evidence for specific effects of leptin on fat distribution and in vivo insulin action. Leptin (LEP) or vehicle (CON) was administered by osmotic minipumps for 8 d to pair-fed adult rats. During the 8 d of the study, body weight and total fat mass decreased similarly in LEP and in CON. However, while moderate calorie restriction (CON) resulted in similar decreases in whole body (by 20%) and visceral (by 21%) fat, leptin administration led to a specific and marked decrease (by 62%) in visceral adiposity. During physiologic hyperinsulinemia (insulin clamp), leptin markedly enhanced insulin action on both inhibition of hepatic glucose production and stimulation of glucose uptake. Finally, leptin exerted complex effects on the hepatic gene expression of key metabolic enzymes and on the intrahepatic partitioning of metabolic fluxes, which are likely to represent a defense against excessive storage of energy in adipose depots. These studies demonstrate novel actions of circulating leptin in the regulation of fat distribution, insulin action, and hepatic gene expression and suggest that it may play a role in the pathophysiology of abdominal obesity and insulin resistance.     

Nicotinic agonists competitively antagonize serotonin at mouse 5-HT3 receptors expressed in Xenopus oocytes

Leptin is an adipocyte-derived blood-borne satiety factor that decreases food intake and increases energy expenditure, thereby leading to a substantial decrease in body weight. To explore the possible roles of the hypothalamic melanocortin system in leptin action, we examined the effects of intracerebroventricular (i.c.v.) injection of leptin with or without SHU9119, a potent antagonist of alpha-melanocyte stimulating hormone, on food intake, body weight, and mitochondrial uncoupling protein-1 (UCP-1) mRNA expression in the brown adipose tissue (BAT) in rats. A single i.c.v. injection of leptin decreased cumulative food intake and body weight gain, and increased UCP-1 mRNA expression during 3 h at the onset of the dark phase. Inhibition of food intake and body weight change with leptin was reversed by co-injection of SHU9119 in a dose-dependent manner. Co-injection of SHU9119 also inhibited completely the leptin-induced increase in UCP-1 mRNA expression in the BAT. Treatment with SHU9119 alone did not affect food intake, body weight, and UCP-1 mRNA expression in rats. The present study provides evidence that the hypothalamic melanocortin system plays a central role in both satiety effect and sympathetic activation of leptin.     

Cell proliferation and esophageal carcinogenesis in the zinc-deficient rat

Target cell proliferation was investigated throughout the development of esophageal cancer induced by N-nitroso-methylbenzylamine (NMBA) in weanling rats maintained on zinc-deficient or sufficient diets. Deficient rats were fed ad libitum, while zinc-sufficient rats were either pair-fed to the deficient animals or fed ad libitum. After 5 weeks, half of the animals in each dietary group were given six intragastric doses of NMBA (2 mg/kg; twice weekly). The remaining rats were untreated by carcinogen. At weeks 1, 2, 3, 4, 5, 7, 9 and 11 post first dose, esophageal cell proliferation was assessed in rats from each group by in vivo bromodeoxyuridine (BrDU) labeling followed by immunohistochemical detection of cells in S-phase. At 11 weeks, the tumor incidence was 100, 23 and 6%, respectively, in the zinc-deficient, zinc-sufficient, ad libitum and pair-fed groups. In vivo BrDU labeling revealed that in the NMBA-untreated groups, the labeling index (LI), the number of labeled cells, and the total number of cells per cross section of entire esophagi were significantly increased by zinc deficiency at all time points; LI was lowest in zinc-sufficient, pair-fed rats. During NMBA treatment (weeks 6, 7 and 8), increased cell proliferation occurred in both groups of zinc-sufficient esophagi but only during week 6 in the deficient ones. In the weeks following the cessation of NMBA treatment, zinc-deficient esophagi showed significantly increased LI and greater number of labeled cells than the carcinogen treated, zinc-sufficient pair-fed or ad libitum fed groups. On the other hand, NMBA-treated zinc-sufficient pair-fed rats showed lower LI and smaller number of labeled cells than their zinc-sufficient ad libitum counterparts. Most importantly, esophageal papillomas were found in two zinc-deficient animals that had received no NMBA treatment, after 10-11 weeks of experimental diet. These data support a direct relationship between cell proliferation and tumor incidence, and also provide evidence that zinc deficiency and its associated cell proliferation could be carcinogenic.     

MitBASE: a comprehensive and integrated mitochondrial DNA database

The mechanisms underlying the increase in energy expenditure during leptin treatment are not clear. We recently showed that a 5-h intravenous or intracerebroventricular infusion of leptin elevated basal glucose uptake in skeletal muscle (SM) and brown adipose tissue and increased whole-body glucose turnover in C57Bl/6J mice (Kamohara S, Burcelin R, Halaas JL, Friedman JM, Charron MJ: Acute stimulation of glucose metabolism in mice by leptin treatment. Nature 389:374-377, 1997). We extended the previous study by measuring steady-state levels of uncoupling protein (UCP)-2 mRNA and UCP-3 mRNA in white adipose tissue (WAT) and SM. Leptin by intravenous or intracerebroventricular infusion for 5 h was associated with a decrease in UCP-2 mRNA in WAT (47-52%) and UCP-3 mRNA in SM (33-37%). Because overexpression of UCP-2 or UCP-3 can depolarize the inner mitochondrial membrane, suppression of UCP-2 mRNA and UCP-3 mRNA may in fact lower respiratory demands in WAT and SM. This is consistent with the parallel suppression of cytochrome oxidase subunit IV (COX-IV) mRNA in WAT (35-39%) after leptin infusion. COX-IV mRNA in SM did not respond to acute leptin treatment. Mitochondrial inorganic phosphate carrier (P1C) mRNA was also suppressed in WAT (33-35%) by either method of leptin infusion, but only intravenous infusion of leptin reduced P1C mRNA in SM (40%). Denervation suppressed mRNA levels for UCP-2 (49%), UCP-3 (36%), and COX-IV (59%) and eliminated the acute response to leptin in SM. The comparable response to leptin under intravenous or intracerebroventricular infusion and the loss of responsiveness after denervation strongly suggest that the acute effects of leptin involve central signaling pathways.     

BCG infection suppresses allergic sensitization and development of increased airway reactivity in an animal model

We previously demonstrated that chronic dietary treatment with acarbose, an alpha-glucosidase inhibitor, improves glucose homeostasis in the streptozotocin (STZ)-induced diabetic rat. In this study we evaluated the effects of 4 weeks of acarbose treatment on glucose homeostasis in STZ-diabetic rats for both meal-fed (three times daily) and ad libitum feeding conditions. Sprague Dawley male rats (n = 58) were started on a daily meal-feeding paradigm consisting of three 2-h feeding periods: 0700 to 0900 hours, 1300 to 1500 hours, and 1900 to 2100 hours. Following 2 weeks of adaptation, half of the animals were switched to ad libitum feeding. The feeding paradigm itself (meal fed versus ad lib.) affected neither body weight nor daily food intake. Twenty animals from each feeding group then received STZ (60 mg/kg i.v.), whereas control animals received vehicle injections only. Two days later, the diet of 10 STZ-treated animals from each paradigm was supplemented with acarbose (40 mg of BAY G 5421/100-g diet), and the groups were treated for 4 weeks. Untreated diabetic rats had lower body weight than vehicle-injected control rats at all time points after STZ treatment. Acarbose treatment delayed this effect on body weight. STZ treatment induced hyperphagia regardless of feeding paradigm, which was significantly attenuated by acarbose only for the first week of treatment. Untreated diabetic rats had fasting blood glucose values 4 times those of vehicle-injected controls in both the meal-fed and ad libitum-fed conditions. Acarbose significantly lowered fasting blood glucose in the treated STZ groups. Blood glucose was also assessed 0, 90, and 180 min following the start of a meal. The postprandial rise in blood glucose was significantly reduced in acarbose-treated meal-fed diabetic rats, to values not significantly different from those of vehicle-injected control rats. During the fourth week of treatment glycated hemoglobin levels were significantly higher in untreated diabetic groups compared to vehicle-injected control groups. Acarbose treatment significantly reduced this rise, regardless of the feeding paradigm. Collectively, the results demonstrate that acarbose reduces diabetes-induced increases of blood glucose and glycated hemoglobin and that the glycemic effects of acarbose are most apparent during the absorptive period. Feeding paradigm (ad lib. versus meal fed) has little or no influence on acarbose's metabolic effects, indicating that large meals are not required to realize the beneficial effects of the drug. The meal-fed STZ-diabetic rat may be a good model with which to test meal-based diabetes treatments.     

Large granular lymphocytic leukemia. Case report with scarce expression in peripheral blood

Evidence is rapidly emerging which suggests that uncoupling protein 2 (UCP2), by virtue of its ubiquitous expression, may be important for determining basal metabolic rate. To assess the functional modulation of UCP2 gene expression in relation to body weight control, we examined the effects of hyperthyroid state induced by chronic treatment with triiodothyronine (T3) on UCP2 mRNA expression in male rats. Daily subcutaneous injection of T3 (37 pmol/100 g body weight) for 7 days increased UCP2 mRNA expression in brown adipose tissue (BAT), white adipose tissue (WAT) and the soleus muscle 1.6-, 1.6- and 1.7-fold compared to the controls, respectively, and increased UCP1 mRNA expression in BAT 1.2-fold. In contrast, the same treatment with T3 decreased both ob mRNA expression in WAT and plasma leptin level 0.5-fold for each. The present results suggest that T3 may directly increase UCP2 expression independently of leptin action.     

Perturbation of fuel homeostasis caused by overexpression of the glucose-6-phosphatase catalytic subunit in liver of normal rats

The terminal step in hepatic gluconeogenesis is catalyzed by glucose-6-phosphatase, an enzyme activity residing in the endoplasmic reticulum and consisting of a catalytic subunit (glucose-6-phosphatase (G6Pase)) and putative accessory transport proteins. We show that Zucker diabetic fatty rats (fa/fa), which are known to exhibit impaired suppression of hepatic glucose output, have 2.4-fold more glucose-6-phosphatase activity in liver than lean controls. To define the potential contribution of increased hepatic G6Pase to development of diabetes, we infused recombinant adenoviruses containing the G6Pase cDNA (AdCMV-G6Pase) or the beta-galactosidase gene into normal rats. Animals were studied by one of three protocols as follows: protocol 1, fed ad libitum for 7 days; protocol 2, fed ad libitum for 5 days, fasted overnight, and subjected to an oral glucose tolerance test; protocol 3, fed ad libitum for 4 days, fasted for 48 h, subjected to oral glucose tolerance test, and then allowed to refeed overnight. Hepatic glucose-6-phosphatase enzymatic activity was increased by 1.6-3-fold in microsomes isolated from AdCMV-G6Pase-treated animals in all three protocols, and the resultant metabolic profile was similar in each case. AdCMV-G6Pase-treated animals exhibited several of the abnormalities associated with early stage non-insulin-dependent diabetes mellitus, including glucose intolerance, hyperinsulinemia, decreased hepatic glycogen content, and increased peripheral (muscle) triglyceride stores. These animals also exhibited significant decreases in circulating free fatty acids and triglycerides, changes not normally associated with the disease. Our studies show that overexpression of G6Pase in liver is sufficient to perturb whole animal glucose and lipid homeostasis, possibly contributing to the development of metabolic abnormalities associated with diabetes.     

Effect of caloric restriction on basal insulin levels and the in vivo lipogenesis and glycogen synthesis from glucose in the Koletsky obese rat

Fasting plasma immunoreactive insulin levels increased with age in hyperinsulinemic Koletsky obese rats, being almost four times as high as in lean siblings at 3 mo (40 +/- 5 muU/ml) and rising steadily to 82 +/- 4 muU/ml at 6 mo (about seven times higher than lean siblings). Restricting the food intake of the obese rats markedly reduced but did not normalize the hyperinsulinemia, which in these rats was accompanied by normal plasma glucose concentrations. The incorporation in vivo of D-U-14C-glucose into tissue lipids and glycogen was measured 1 hr after the intravenous injection of 1 g glucose (containing 100 muDi D-U-14C-glucose) per kg body weight in obese rats eating ad libitum, obese rats after 3 mo on a restricted food intake, and lean siblings. All tissues (heart, diaphragm, skeletal muscle, and adipose tissues and liver) of obese rats exhibited a significantly greater lipogenesis from glucose than those of lean siblings. Dietary restriction of the obese rats reduced the 14C incorporation into lipid to levels not significantly different from lean controls in all tissues except skeletal muscle and liver, where, although greatly reduced, lipogenesis was still significantly higher than in lean rats. Glycogen synthesis tended to be greater in all tissues of obese rats than in lean animals. Dietary restriction of obese rats did not greatly affect glycogen synthesis.     

Specificity of leptin action on elevated blood glucose levels and hypothalamic neuropeptide Y gene expression in ob/ob mice

Correction of the obese state induced by genetic leptin deficiency reduces elevated levels of both blood glucose and hypothalamic neuropeptide Y (NPY) mRNA in ob/ob mice. To determine whether these responses are due to a specific action of leptin or to the reversal of the obese state, we investigated the specificity of the effect of systemic leptin administration to ob/ob mice (n = 8) on levels of plasma glucose and insulin and on hypothalamic expression of NPY mRNA. Saline-treated controls were either fed ad libitum (n = 8) or pair-fed to the intake of the leptin-treated group (n = 8) to control for changes of food intake induced by leptin. The specificity of the effect of leptin was further assessed by 1) measuring NPY gene expression in db/db mice (n = 6) that are resistant to leptin, 2) measuring NPY gene expression in brain areas outside the hypothalamus, and 3) measuring the effect of leptin administration on hypothalamic expression of corticotropin-releasing hormone (CRH) mRNA. Five daily intraperitoneal injections of recombinant mouse leptin (150 micrograms) in ob/ob mice lowered food intake by 56% (P < 0.05), body weight by 4.1% (P < 0.05), and levels of NPY mRNA in the hypothalamic arcuate nucleus by 42.3% (P < 0.05) as compared with saline-treated controls. Pair-feeding of ob/ob mice to the intake of leptin-treated animals produced equivalent weight loss, but did not alter expression of NPY mRNA in the arcuate nucleus. Leptin administration was also without effect on food intake, body weight, or NPY mRNA levels in the arcuate nucleus of db/db mice. In ob/ob mice, leptin did not alter NPY mRNA levels in cerebral cortex or hippocampus or the expression of CRH mRNA in the hypothalamic paraventricular nucleus (PVN). Leptin administration to ob/ob mice also markedly reduced serum glucose (8.3 +/- 1.2 vs. 24.5 +/- 3.8 mmol/l; P < 0.01) and insulin levels (7,263 +/- 1,309 vs. 3,150 +/- 780 pmol/l), but was ineffective in db/db mice. Pair-fed mice experienced reductions of glucose and insulin levels that were < 60% of the reduction induced by leptin. The results suggest that in ob/ob mice, systemic administration of leptin inhibits NPY gene overexpression through a specific action in the arcuate nucleus and exerts a hypoglycemic action that is partly independent of its weight-reducing effects. Furthermore, both effects occur before reversal of the obesity syndrome. Defective leptin signaling due to either leptin deficiency (in ob/ob mice) or leptin resistance (in db/db mice) therefore leads directly to hyperglycemia and the overexpression of hypothalamic NPY that is implicated in the pathogenesis of the obesity syndrome.     

Alcohol consumption by young actively growing rats: a study of cortical bone histomorphometry and mechanical properties

Alcohol consumption by young actively growing rats has been previously demonstrated to decrease cortical and cancellous bone density, to reduce trabecular bone volume, and to inhibit bone growth at the epiphyseal growth plate. This study addresses the action of alcohol on cortical bone growth using histomorphometric techniques and on mechanical properties by three-point bending. Four-week-old, female Sprague-Dawley rats were divided into three groups. Alcohol-treated animals were fed a modified Lieber-DeCarli diet ad libitum containing 35% ethanol-derived calories, whereas the pair-fed animals (weight-matched to ethanol rats) received an isocaloric liquid diet in which maltose-dextrin-substituted calories were supplied by ethanol. Chow animals were fed a standard rat chow ad libitum. Femora were removed for analysis after 2, 4, 6, or 8 weeks on the diets. Cortical bone area, bone formation rates, and mineral apposition rates were reduced in the alcohol-fed animals. Bone stiffness, strength, and energy absorbed to fracture were significantly lower in the alcohol-fed animals. This distinctive alcohol effect was revealed to be caused by lower quality bone tissue as reflected by lower elastic moduli and yield strengths.     

Validation of cues for competencies of beginning level mental health nurses: an exploratory study in South Australian mental health agencies

The purpose of this study was to test whether serum testosterone (T) concentrations characteristic of reproductively active, long-day-housed Siberian hamsters are necessary for compensatory increases in nonexcised fat pads following removal of epididymal white adipose tissue (EWAT) and/or for the maintenance of seasonally appropriate body weights in these hamsters. Long-day-housed hamsters were castrated or left intact, sham or EWAT lipectomized, and given T or cholesterol (C) implants. All groups had ad libitum food access except for two castrated T-treated groups that were pair-fed to their C-treated counterparts to control for effects of T on food intake. C-treated castrates had decreased body weights compared with all other groups, suggesting a role of T in the maintenance of seasonally appropriate body mass. Since the T-treated hamsters pair-fed to these T-deficient animals exhibited seasonally appropriate body weights and fat pad masses, T does not appear to affect these parameters through the modulation of food intake. All fat pads of C-treated animals were smaller than those of ad libitum- or pair-fed, T-treated castrates; however, EWAT was the only fat pad that was smaller in the C-treated sham-lipectomized group than in gonad-intact sham-lipectomized hamsters. This result may indicate an enhanced sensitivity of EWAT to T. The effects of T on fat pad mass were not associated with proportionate changes in lipoprotein lipase activity, suggesting that the major effect of T on fat accumulation occurs through other mechanisms in this species. C-treated lipectomized hamsters compensated for the body fat deficit 8 weeks after lipectomy via statistically non-significant increases in retroperitoneal and inguinal WAT mass. This finding suggests that, whereas T is necessary for maintenance of seasonally-appropriate body weight, it is not necessary for fat pad compensation after EWAT lipectomy.     

Plasma leptin in diabetic and insulin-treated diabetic and normal rats

Adipose tissue leptin mRNA levels are decreased by food deprivation or induction of insulin-deficient diabetes. To determine whether plasma leptin concentrations are similarly affected, whether treatment of diabetes with insulin restores plasma leptin, and whether this requires restoration of body weight (lost as a result of diabetes) and/or normalization of glycemia, we measured plasma leptin concentrations in control, untreated streptozotocin (STZ)-diabetic, and insulin-treated STZ-diabetic rats. Plasma leptin was markedly reduced in untreated STZ-diabetic rats. Insulin treatment for 4 to 17 days increased plasma leptin approximately twofold above control levels. However, despite the hyperleptinemia, insulin-treated diabetic rats gained weight at a rate equal to that of sham-treated controls. Epididymal adipose tissue leptin mRNA levels in 17-day insulin-treated diabetic rats were equal to but did not exceed sham-control levels, unlike plasma leptin. Plasma glucose concentrations in insulin-treated STZ-diabetic rats were lower than in sham controls. Therefore, to determine whether hypoglycemia may be important in increasing plasma leptin, we measured plasma leptin levels in diabetic rats infused with insulin for 3 hours along with a variable-rate glucose infusion targeting glycemia to 200 or 40 mg/100 mL. Plasma leptin rapidly increased in these rats irrespective of target glycemia. Plasma leptin also increased rapidly in normal rats infused with insulin and glucose (target glycemia, 200 mg/100 mL). We conclude that plasma leptin concentrations are markedly reduced under conditions of insulin deficiency and rapidly increased by insulin treatment. The increase in plasma leptin does not require restoration of body weight and, under glucose clamp conditions, does not depend on target glycemia. Hyperleptinemia in insulin-treated diabetic rats is not explained on the basis of steady-state leptin mRNA levels, at least as reflected in epididymal fat.