Differential effects of glucocorticoids on energy homeostasis in Syrian hamsters

Syrian hamsters, like many humans, increase food intake and body adiposity in response to stress. We hypothesized that glucocorticoids (cortisol and corticosterone) mediate these stress-induced effects on energy homeostasis. Because Syrian hamsters are dual secretors of cortisol and corticosterone, differential effects of each glucocorticoid on energy homeostasis were investigated. First, adrenal intact hamsters were injected with varying physiological concentrations of cortisol, corticosterone, or vehicle to emulate our previously published defeat regimens (i.e., 1 injection/day for 5 days). Neither food intake nor body weight was altered following glucocorticoid injections. Therefore, we investigated the effect of sustained glucocorticoid exposure on energy homeostasis. This was accomplished by implanting hamsters with supraphysiological steady-state pellets of cortisol, corticosterone, or cholesterol as a control. Cortisol, but not corticosterone, significantly decreased food intake, body mass, and lean and fat tissue compared with controls. Despite decreases in body mass and adiposity, cortisol significantly increased circulating free fatty acids, triglyceride, cholesterol, and hepatic triglyceride concentrations. Although corticosterone did not induce alterations in any of the aforementioned metabolic end points, Syrian hamsters were responsive to the effects of corticosterone since glucocorticoids both induced thymic involution and decreased adrenal mass. These findings indicate that cortisol is the more potent glucocorticoid in energy homeostasis in Syrian hamsters. However, the data suggest that cortisol alone does not mediate stress-induced increases in food intake or body mass in this species.     

Ovariectomized hamster: a potential model of postmenopausal hypercholesterolemia

A suitable and economical animal model of ovarian hormone deficiency can greatly enhance the understanding of postmenopausal-elevated risk of coronary heart disease. The male Golden Syrian hamster is a well-established small animal model of hypercholesterolemia, but the effect of ovariectomy on lipid profile in the female hamster is unclear. The objective of this study was to determine whether ovariectomized hamsters develop hypercholesterolemia and experience changes in body fat distribution consistent with changes observed in postmenopausal women. Twenty-two 90-day-old female Golden Syrian hamsters were divided into two groups and were either ovariectomized or sham-operated and given free access to a standard cholesterol-free laboratory diet for 65 days. Ovariectomized hamsters had significantly (P < 0.05) elevated serum total cholesterol concentrations (16.6%) as well as abdominal fat mass (56%; P< 0.01) despite equal food intake compared with the sham-operated group. In contrast, the mean intestinal weight and in vivo rate of sterol biosynthesis were significantly (P < 0.002 and P = 0.01, respectively) lower in the ovariectomized compared with the sham-operated group. In vivo rates of hepatic sterol biosynthesis were directionally lower (P = 0.1) in the ovariectomized group. No significant differences were observed in final body weight, serum triglycerides, or liver total cholesterol and lipids between the two groups. In conclusion, ovariectomized hamsters undergo changes in serum cholesterol and fat distribution similar to those experienced by postmenopausal women, and thus may serve as an appropriate model for postmenopausal hypercholesterolemia.     

Subcutaneous lipectomy causes a metabolic syndrome in hamsters

The insulin resistance syndrome X is related to excess intra-abdominal adipose tissue. With lipectomy of >50% of subcutaneous adipose tissue (SQAT) in nonhibernating, adult female Syrian hamsters on high-fat (HF; 50 calorie%) diet and measurements of oral glucose tolerance, oral [(14)C]oleic acid disposal, serum triglycerides, serum leptin, liver fat, perirenal (PR) adipose tissue cellularity, and body composition, we studied the role of SQAT. Sham-operated (S) animals on HF or low-fat (LF; 12.5 calorie%) diets served as controls. After 3 mo there was no visible regrowth of SQAT but HF diet led to similar levels of body weight and body fat in lipectomized and sham-operated animals. Lipectomized (L) animals had more intra-abdominal fat as a percentage of total body fat, higher insulinemic index, a strong trend toward increased liver fat content, and markedly elevated serum triglycerides compared with S-HF and S-LF. Liver and PR adipose tissue uptake of fatty acid were similar in L-HF and S-HF but reduced vs. S-LF, and were inversely correlated with liver fat content and insulin sums during the oral glucose tolerance test. In summary, lipectomy of SQAT led to compensatory fat accumulation implying regulation of total body fat mass. In conjunction with HF diet these lipectomized hamsters developed a metabolic syndrome with significant hypertriglyceridemia, relative increase in intra-abdominal fat, and insulin resistance. We propose that SQAT, via disposal and storage of excess ingested energy, acts as a metabolic sink and protects against the metabolic syndrome of obesity.     

Reductions of body fat stores and total plasma cholesterol and triglyceride concentrations in several species by bromocriptine treatment

Administrations (injections and in feed) of bromocriptine, a dopamine agonist that inhibits prolactin secretion, reduced body fat stores and plasma total cholesterol and triglyceride concentrations in several rodent species (Syrian hamsters, Djungarian hamsters, Swiss Webster mice and obese Zucker rats). Body fat indices were reduced by at least 50% in the hamsters and mice within 10-15 days of treatment and by 29% in 8 weeks in the rats. Bromocriptine reduced total plasma cholesterol concentration by 17% in Syrian hamsters, 41% in mice and 30% in rats fasted before blood sampling. In nonfasted obese rats, bromocriptine dramatically reduced both cholesterol (from 440 to 130 mg/dl) and triglyceride (from 1570 to 540 mg/dl) levels compared with controls. These findings offer further evidence for a primary role of prolactin in lipid metabolism and indicate that bromocriptine may be useful for treating obesity and lipid-based cardiovascular disorders.     

Hormonal modulation of pineal melatonin synthesis in rats and Syrian hamsters: effects of streptozotocin-induced diabetes and insulin injections

Pineal levels of tryptophan, 5-hydroxytryptophan, serotonin, N-acetylserotonin, melatonin, 5-hydroxyindoleacetic acid and the enzyme activities of N-acetyltransferase and hydroxyindole-O-methyltransferase were determined in male albino rats and Syrian hamsters that were injected with insulin twice daily for three days, or injected with streptozotocin to induce diabetes. Neither insulin injections nor streptozotocin diabetes had any effect on pineal melatonin production in rats. In hamsters, diabetes reduced the nocturnal peak of pineal melatonin content by approximately one half, while insulin injections had no effect on pineal melatonin levels; however, insulin injections did cause a slight increase in pineal N-acetyltransferase activity. These findings indicate that the pineal gland of the hamster may be more sensitive to alterations in plasma insulin levels than the same organ in rats.     

Social defeat increases food intake, body mass, and adiposity in Syrian hamsters

Overeating and increases in body and fat mass are the most common responses to day-to-day stress in humans, whereas stressed laboratory rats and mice respond oppositely. Group housing of Syrian hamsters increases body mass, adiposity, and food intake, perhaps due to social confrontation-induced stress. In experiment 1 we asked, Does repeated social defeat increase food intake, body mass, and white adipose tissue (WAT) mass in Syrian hamsters? Male hamsters subjected to the resident-intruder social interaction model and defeated intermittently 15 times over 34 days for 7-min sessions significantly increased their food intake, body mass, and most WAT masses compared with nondefeated controls. Defeat significantly increased terminal adrenal norepinephrine, but not epinephrine, content. In experiment 2 we asked, Are 15 intermittent resident-intruder interactions necessary to increase body mass and food intake? Body mass and food intake of subordinate hamsters defeated only once were similar to those of nondefeated controls, but four or eight defeats similarly and significantly increased these responses. In experiment 3 we asked, Do intermittent defeats increase adiposity and food intake more than consecutive defeats? Four intermittent or consecutive defeats similarly and significantly increased food intake and body mass compared with nondefeated controls, but only intermittent defeats significantly increased all WAT masses. Consecutive defeats significantly increased mesenteric and inguinal WAT masses. Plasma leptin, but not insulin, concentrations were similarly and significantly increased compared with nondefeated controls. Collectively, social defeat, a natural stressor, significantly increased food intake, body mass, and adiposity in Syrian hamsters and may prove useful in determining mechanisms underlying human stress-induced obesity.     

Temporal Synergism of Corticosterone and Prolactin in the Syrian Hamster, Mesocricetus auratus

To augment the limited work reported in the literature regarding testing of the hormonal temporal synergism hypothesis in Syrian hamsters (Joseph MM, Meier AH. Proc Soc Exp Biol Med. 1974;146:1150-5), a large experiment with female hamsters was conducted. Forty-eight received corticosterone at 18:00 h on January 21, 23, 25, 27, and 29 and ovine prolactin at one of six times of day beginning January 22 for 8 days; 36 received saline (at 18:00) and prolactin at one of the six times of day for 8 days; 35 received only prolactin at one of the six times of day for 8 days; and 16 received no injections. Twelve hamsters receiving corticosterone and prolactin and eight uninjected hamsters were on running wheels. The corticosterone and prolactin group not on wheels had a body weight gain and no circadian rhythm of weight gain, but did have circadian rhythms of response in organ weight, per 100 g of body weight, and in weights of fat pads and uteri. The corticosterone and prolactin group with access to running wheels gained in body weight and had larger ovaries and smaller fat pads. Hamsters receiving saline and prolactin had a body weight gain, but had no circadian rhythms of response in organ weights. The hamsters receiving only prolactin gained in body weight but had no rhythms of response, except for unexpected circadian rhythms in body weight gain and weights of fat pads. The uninjected hamsters had a modest weight gain. Most or all hamsters with access to running wheels freeran, and the corticosterone injections did not appear to synchronize the locomotor activity rhythms. In conclusion, corticosterone does interact with the injection time effect of prolactin on weights of fat pads, paired ovaries, and uteri. The mechanism of that effect, in terms of circadian rhythm theory, is unclear.     

Temporal Synergism of Corticosterone and Prolactin in the Syrian Hamster,Mesocricetus auratus

To augment the limited work reported in the literature regarding testing of the hormonal temporal synergism hypothesis in Syrian hamsters (Joseph MM, Meier AH. Proc Soc Exp Biol Med. 1974;146:1150-5), a large experiment with female hamsters was conducted. Forty-eight received corticosterone at 18:00 h on January 21, 23, 25, 27, and 29 and ovine prolactin at one of six times of day beginning January 22 for 8 days; 36 received saline (at 18:00) and prolactin at one of the six times of day for 8 days; 35 received only prolactin at one of the six times of day for 8 days; and 16 received no injections. Twelve hamsters receiving corticosterone and prolactin and eight uninjected hamsters were on running wheels. The corticosterone and prolactin group not on wheels had a body weight gain and no circadian rhythm of weight gain, but did have circadian rhythms of response in organ weight, per 100 g of body weight, and in weights of fat pads and uteri. The corticosterone and prolactin group with access to running wheels gained in body weight and had larger ovaries and smaller fat pads. Hamsters receiving saline and prolactin had a body weight gain, but had no circadian rhythms of response in organ weights. The hamsters receiving only prolactin gained in body weight but had no rhythms of response, except for unexpected circadian rhythms in body weight gain and weights of fat pads. The uninjected hamsters had a modest weight gain. Most or all hamsters with access to running wheels freeran, and the corticosterone injections did not appear to synchronize the locomotor activity rhythms. In conclusion, corticosterone does interact with the injection time effect of prolactin on weights of fat pads, paired ovaries, and uteri. The mechanism of that effect, in terms of circadian rhythm theory, is unclear.     

Phospholipid base exchange enzyme activity in sarcolemmal membranes from the heart of cardiomyopathic hamsters

The activity of phospholipid base exchange enzymes has been evaluated in cardiac sarcolemmal membranes from Syrian Golden hamsters and from a hamster strain (UM-X7.1) characterized by a genetic form of hypertrophic cardiomyopathy. No choline base exchange activity and only a little serine base exchange activity were detected, whereas the ethanolamine base exchange enzyme was found highly active in membranes from both strains. For this reason, the present study is focussed on the ethanolamine base exchange enzyme. The apparent Km for ethanolamine of ethanolamine base exchange enzyme from Syrian Golden membranes and from UM-X7.1 strain membranes are 18 and 32 μM, respectively. The specific activity of the sarcolemmal ethanolamine base exchange enzyme is lower in the UM-X7.1 strain than in Syrian Golden hamsters. The calcium-dependence of the enzyme appears different when the membranes from the two strains are compared. Indeed, after removal of the membrane-bound divalent cations, comparable activities are found in both membrane preparations, whereas, upon addition of Ca²⁺ to the incubation mixtures, the activity of the enzyme is enhanced in the membranes from Syrian Golden strain more than in those from UM-X7.1 strain. The cholesterol content of sarcolemmal membranes is higher in the cardiomyopathic strain than in the Syrian Golden hamsters. A possible relation between changes of the membrane lipid composition and of the ethanolamine base exchange activity is discussed.     

Reproductive effects of 6-chloromelatonin implants and/or injections in male and female Syrian hamsters (Mesocricetus auratus)

Adult female hamsters were injected each afternoon for 9 weeks with 2.5, 15 or 25 micrograms of melatonin or 6-chloromelatonin (CM). Each drug resulted in a significant dose-related depression in uterine, ovarian and anterior pituitary gland weights. Additionally, plasma and pituitary concentrations of prolactin fell with increasing dose of either indole whereas pituitary levels of LH and FSH were positively correlated with dose. There was no difference in effectiveness between the two drugs. Adult male hamsters treated for 10 weeks with daily afternoon injections of melatonin and a blank beeswax pellet had depressed testicular and accessory organ weights and plasma and pituitary concentrations of prolactin. Implantation of a 1 mg melatonin or CM beeswax pellet in hamsters concurrently receiving daily afternoon injections of melatonin prevented the organ weight and hormonal changes, except for plasma prolactin. Adult male hamsters treated for 10 weeks with daily afternoon injections of CM and a blank beeswax pellet had depressed reproductive organ weights and pituitary and plasma concentrations of prolactin; this depression in hormonal values and organ weights was totally prevented if the CM-injected hamsters were also bearing a beeswax-melatonin pellet. In conclusion, 6-chloromelatonin is as effective as melatonin with regards to antigonadotrophic and counter-antigonadotrophic effects in male and female Syrian hamsters.     

Thermoregulatory responses of dystrophic hamsters to changes in ambient temperatures

The ability of dystrophic hamsters to maintain their body temperature despite abnormal muscle and brown adipose tissue, two organs involved in thermoregulation, was evaluated. Dystrophic hamsters (CHF 146) between the ages of 30 and 160 days kept at 21 degrees C had core (rectal) temperatures (TR) that were 0.5-1.5 degrees C lower than Golden Syrian controls. The reduced core temperatures of dystrophic hamsters were unlikely the result of an incapacity to generate heat since the dystrophic hamsters were able to maintain their TRs during 3 h of acute cold stress (4 degrees C) and to adapt to prolonged cold exposure. However, TRs of cold-acclimated dystrophic hamsters were still 1 degree C below TRs of cold-acclimated control animals. By contrast, increasing the ambient temperature raised TRs of both normal and dystrophic hamsters. When kept at 32 degrees C overnight, the TRs of dystrophic hamsters remained significantly below those of control animals. When heat-exposed dystrophic hamsters were returned to 21 degrees C, their TRs returned to values significantly lower than those of control hamsters. Thus, dystrophic hamsters showed a capacity to thermoregulate, like control hamsters, but appeared to do so at a lower temperature. The reduced core temperatures of dystrophic hamsters kept at 21 degrees C cannot be explained by a reduction in metabolic activity since newborns and 30- and 140-day-old dystrophic hamsters had rates of oxygen consumption (VO2) and carbon dioxide production (VCO2) that were similar to those of controls. These results suggest that the thermoregulatory set point may be altered in dystrophic hamsters.     

Defective activity and isoform of the Na,K-ATPase in the dilated cardiomyopathic hamster.

The Na,K-ATPase function appears impaired in human heart failure with dilation; however little is known in animal model with idiopathic dilated cardiomyopathy. We studied Na,K-ATPase isoform composition and activity from cardiomyopathic hamsters of the MS 200 strain with pure dilated cardiomyopathy and compared them with those of healthy Syrian hamsters. 150-day-old male MS 200 Syrian hamsters (n = 16) and sex- and age-matched healthy Syrian hamsters (n = 15) were used. Antibodies specific for the three alpha-isoforms and against the beta1-isoform were used to study Na,K-ATPase isoform expression in ventricular myocardium. Na,K-ATPase activity was quantified in homogenate and membrane fractions. There was no significant change in left ventricular mass. Morphological examination revealed a decreased septum thickness in the dilated cardiomyopathy compared with control hamster. Idiopathic dilated cardiomyopathy in hamsters presented significantly reduced membrane alpha1 and beta1 abundances and reduced Na,K-ATPase activity (-35% vs. healthy control, p<0.05). Chronic heart failure had no effect on the Na,K-ATPase alpha2-subunit protein. We have demonstrated for the first time that dilated cardiomyopathy induces a specific reduction of both membrane alpha1- and beta1-isoform abundance and Na,K-ATPase activity in hamsters similar to those previously reported in human dilated heart failure.     

Social defeat and footshock increase body mass and adiposity in male Syrian hamsters

Obesity is a world-wide epidemic, and many factors, including stress, have been linked to this growing trend. After social stress (i.e., defeat), subordinate laboratory rats and most laboratory mice become hypophagic and, subsequently, lose body mass; the opposite is true of subordinate Syrian hamsters. After social defeat, Syrian hamsters become hyperphagic and gain body mass compared with nonstressed controls. It is unknown whether this increase in body mass and food intake is limited to subordinate hamsters. In experiment 1, we asked, do dominant hamsters increase food intake, body mass, and adiposity after an agonistic encounter? Subordinate hamsters increased food intake and body mass compared with nonstressed controls. Although there was no difference in food intake or absolute body mass between dominant and nonstressed control animals, cumulative body mass gain was significantly higher in dominant than in nonstressed control animals. Total carcass lipid and white adipose tissue (WAT) (i.e., retroperitoneal and epididymal WAT) masses were significantly increased in subordinate, but not dominant, hamsters compared with nonstressed controls. In experiment 2, we asked, does footshock stress increase food intake, body mass, and adiposity. Hamsters exposed to defeat, but not footshock stress, increased food intake relative to nonstressed controls. In animals exposed to defeat or footshock stress, body mass, as well as mesenteric WAT mass, increased compared with nonstressed controls. Collectively, these data demonstrate that social and nonsocial stressors increase body and lipid mass in male hamsters, suggesting that this species may prove useful for studying the physiology of stress-induced obesity in some humans.     

Melatonin Accelerates Reentrainment After Phase Advance of the Light-dark Cycle in Syrian Hamsters: Antagonism by Flumazenil

The objective of this study was to assess whether melatonin injections accelerated reentrainment of locomotor activity and body temperature rhythms of Syrian hamsters after phase-advancing the light-dark (L:D) cycle and to what extent the effect can be modified by the benzodiazepine (BZP) receptor antagonist flumazenil. After a baseline recording of rhythms, a 6-h phase advance of the L:D cycle was made (day D). Groups of hamsters were subjected, on days D -2, D -1, and D, to one of the following treatments: two injections of vehicle 15 min apart; vehicle followed 15 min later by melatonin (1 mg/kg); flumazenil (5 mg/kg) followed 15 min later by vehicle; or flumazenil (5 mg/kg) followed 15 min later by melatonin (1 mg/kg). Injections were given at the expected time of lights off after the phase shift. In vehicle-injected and untreated controls, ～ 1 day per hour of phase advance was needed to resynchronize the rhythms. The administration of melatonin brought about a significant decrease of resynchronization time to 66% of vehicle-injected controls. The effect of melatonin was prevented by first administering flumazenil. Flumazenil, injected alone, did not modify resynchronization after the shift. The results agree with the view that melatonin activity on circadian rhythmicity is sensitive to central-type BZP antagonism.     

Melatonin Accelerates Reentrainment After Phase Advance of the Light-dark Cycle in Syrian Hamsters: Antagonism by Flumazenil

The objective of this study was to assess whether melatonin injections accelerated reentrainment of locomotor activity and body temperature rhythms of Syrian hamsters after phase-advancing the light-dark (L:D) cycle and to what extent the effect can be modified by the benzodiazepine (BZP) receptor antagonist flumazenil. After a baseline recording of rhythms, a 6-h phase advance of the L:D cycle was made (day D). Groups of hamsters were subjected, on days D -2, D -1, and D, to one of the following treatments: two injections of vehicle 15 min apart; vehicle followed 15 min later by melatonin (1 mg/kg); flumazenil (5 mg/kg) followed 15 min later by vehicle; or flumazenil (5 mg/kg) followed 15 min later by melatonin (1 mg/kg). Injections were given at the expected time of lights off after the phase shift. In vehicle-injected and untreated controls, ∼ 1 day per hour of phase advance was needed to resynchronize the rhythms. The administration of melatonin brought about a significant decrease of resynchronization time to 66% of vehicle-injected controls. The effect of melatonin was prevented by first administering flumazenil. Flumazenil, injected alone, did not modify resynchronization after the shift. The results agree with the view that melatonin activity on circadian rhythmicity is sensitive to central-type BZP antagonism.     

Metabolic control of food intake and estrous cycles in syrian hamsters. I. Plasma insulin and leptin

The "adipostat hypothesis" refers to the idea that circulating hormone concentrations reflect levels of body adiposity and act as signals to control food intake and reproduction. Implicit in the adipostatic hypothesis are the following two assumptions: 1) plasma levels of adipostatic hormones accurately reflect body fat content and 2) decreased plasma concentrations of adipostatic hormones necessarily result in increased food intake and inhibited reproductive processes. The present experiments are designed to test these assumptions. Fat and lean Syrian hamsters were either fasted for 12, 24, 36, or 48 h or allowed ad libitum access to food. Contrary to the first assumption, plasma leptin and insulin levels in fat hamsters dropped dramatically by 12 h after the start of a fast, with no significant change in body fat content and no postfast hyperphagia. Lean hamsters showed anestrus after a 48-h fast but not after a 24-h fast. Contrary to the second assumption of the lipostatic hypothesis, lean hamsters fasted for 24 h and then refed for the next 24 h had leptin levels that were not significantly elevated compared with those of 48-h-fasted hamsters. Thus, in adult female Syrian hamsters, plasma leptin concentrations do not accurately reflect body fat content under all conditions; normal estrous cyclicity does not necessarily require plasma leptin concentrations higher than those of fasted hamsters; and decreased plasma leptin levels do not result in increased food intake.     

Body surface area of the golden Syrian hamster.

The body surface areas (BSAs) of 30 Syrian hamsters were actually measured. From these areas, the Mass Coefficients (K values) for the Dubois and Dubois equation (5.31) and for the Meeh-Rubner equation (11.89), were computed. These values were independent of weight and sex. To verify the applicability of the Mass Coefficients, the BSAs of another 20 animals were calculated and compared with the actually measured BSAs. The difference between measured and calculated BSAs was not significant. Therefore, these values can be used with their respective equations to compute BSA in Golden Syrian hamsters.     

Changes in contractile properties of muscles receiving repeat injections of botulinum toxin (Botox)

Botulinum toxin type A (BTX-A) is a frequently used therapeutic tool to denervate muscles in the treatment of neuromuscular disorders. Although considered safe by the US Food and Drug Administration, BTX-A can produce adverse effects in target and non-target muscles. With an increased use of BTX-A for neuromuscular disorders, the effects of repeat injections of BTX-A on strength, muscle mass and structure need to be known. Therefore, the purpose of this study was to investigate the changes in strength, muscle mass and contractile material in New Zealand White (NZW) rabbits. Twenty NZW rabbits were divided into 4 groups: control and 1, 3 and 6 months of unilateral, repeat injections of BTX-A into the quadriceps femoris. Outcome measures included knee extensor torque, muscle mass and the percentage of contractile material in the quadriceps muscles of the target and non-injected contralateral hindlimbs. Strength in the injected muscles was reduced by 88%, 89% and 95% in the 1, 3 and 6 months BTX-A injected hindlimbs compared to controls. Muscle mass was reduced by 50%, 42% and 31% for the vastus lateralis (VL), rectus femoris (RF) and vastus medialis (VM), respectively, at 1 month, by 68%, 51% and 50% at 3 months and by 76%, 44% and 13% at 6 months. The percentage of contractile material was reduced for the 3 and 6 months animals to 80–64%, respectively, and was replaced primarily by fat. Similar, but less pronounced results were also observed for the quadriceps muscles of the contralateral hindlimbs, suggesting that repeat BTX-A injections cause muscle atrophy and loss of contractile tissue in target muscles and also in non-target muscles that are far removed from the injection site.     

Lovastatin is hypertriglyceridemic in Syrian golden hamsters

The effects of a potent HMG CoA reductase inhibitor, lovastatin, was studied in male Syrian Golden hamsters. Lovastatin (0.1% in food for 6 days) increased hamster serum triglycerides by 12-fold with 2.4-fold increase in serum cholesterol. On continuous treatment serum triglyceride and cholesterol levels gradually decreased to below control values by 12-18 days. When hamsters were fed a mixture of lovastatin and Na-mevalonate no increase in serum triglyceride was observed. [14C]Cholesterol synthesis was increased by 266-fold in livers of hamsters fed lovastatin for 6 days. The increased synthesis of endogenous mevalonate metabolites may be a reason for the decrease in triglyceride levels after 6 days in our studies. The present study suggests that a mevalonate metabolite(s) is necessary for normal triglyceride metabolism in hamsters.     

PKC translocation and ERK1/2 activation in compensated right ventricular hypertrophy secondary to chronic emphysema.

Background  

Right ventricular hypertrophy (RVH) is an important complication of chronic lung disease. However, the signal transduction pathways involved as well as the physiological changes to the right ventricle have not been investigated. Emphysema was produced in male, Syrian Golden hamsters by intra-tracheal instillation of 250 IU/kg elastase (Emp, n = 17). Saline treated animals served as controls (Con, n = 15).