Physico-chemical properties of a novel (—)-hydroxycitric acid extract and its effect on body weight,selected organ weights,hepatic lipid peroxidation and DNA fragmentation,hematology and clinical chemistry,and histopathological changes over a period of 90 days

Garcinia cambogia-derived (—)-hydroxycitric acid (HCA) is a popular and natural supplement for weight management. HCA is a competitive inhibitor of the enzyme ATP citrate lyase, which catalyzes the conversion of citrate and coenzyme A to oxaloacetate and acetyl coenzyme A (acetyl CoA) in the cytosol. Acetyl CoA is used in the synthesis of fatty acids, cholesterol and triglycerides, and in the synthesis of acetylcholine in the central nervous system. Studies have demonstrated the efficacy of a novel 60% calcium-potassium salt of HCA derived from Garcinia cambogia(HCA-SX, Super CitriMax) in weight management. Results have shown that HCA-SX promotes fat oxidation, enhances serotonin release and availability in the brain cortex, normalizes lipid profiles, and lowers serum leptin levels in obese subjects. Acute oral, acute dermal, primary dermal irritation and primary eye irritation toxicity, as well as Ames bacterial reverse mutation studies and mouse lymphoma tests have demonstrated the safety of HCA-SX. However, no detailed long-term safety of HCA-SX or any other HCA extract has been previously assessed. We evaluated the dose- and time-dependent effects of HCA-SX in Sprague-Dawley rats on body weight, selected organ weights, hepatic lipid peroxidation and DNA fragmentation, hematology and clinical chemistry over a period of 90 days. Furthermore, a 90-day histopathological evaluation was conducted. The animals were treated with 0, 0.2, 2.0 and 5.0% HCA-SX of feed intake and were sacrificed on 30, 60 or 90 days of treatment. The body weight and selected organ weights were assessed and correlated as a % of body weight and brain weight at 90 days of treatment. A significant reduction in body weight was observed in treated rats as compared to control animals. An advancing age-induced marginal increase in hepatic lipid peroxidation was observed in both male and female rats, while no such difference in hepatic DNA fragmentation was observed as compared to the control animals. Furthermore, selected organ weights individually and as a % of body weight and brain weight at 90 days of treatment exhibited no significant difference between the groups. No difference was observed in hematology and clinical chemistry or the histopathological evaluation. Taken together, these results show that 90 day treatment of HCA-SX results in a reduction in body weight, and does not cause any changes in major organs or in hematology, clinical chemistry, and histopathology.     

Dose- and time-dependent effects of a novel (−)-hydroxycitric acid extract on body weight,hepatic and testicular lipid peroxidation,DNA fragmentation and histopathological data over a period of 90 days

(–)-Hydroxycitric acid (HCA), a natural extract from the dried fruit rind of Garcinia cambogia (family Guttiferae), is a popular supplement for weight management. The dried fruit rind has been used for centuries as a condiment in Southeastern Asia to make food more filling and satisfying. A significant number of studies highlight the efficacy of Super CitriMax (HCA-SX, a novel 60% calcium-potassium salt of HCA derived from Garcinia cambogia) in weight management. These studies also demonstrate that HCA-SX promotes fat oxidation, inhibits ATP-citrate lyase (a building block for fat synthesis), and lowers the level of leptin in obese subjects. Acute oral, acute dermal, primary dermal irritation and primary eye irritation toxicity studies have demonstrated the safety of HCA-SX. However, no long-term safety of HCA-SX or any other (–)-hydroxycitric acid extract has been previously assessed. In this study, we have evaluated the dose- and time-dependent effects of HCA-SX in Sprague-Dawley rats on body weight, hepatic and testicular lipid peroxidation, DNA fragmentation, liver and testis weight, expressed as such and as a % of body weight and brain weight, and histopathological changes over a period of 90 days. The animals were treated with 0, 0.2, 2.0 and 5.0% HCA-SX as feed intake and the animals were sacrificed on 30, 60 or 90 days of treatment. The feed and water intake were assessed and correlated with the reduction in body weight. HCA-SX supplementation demonstrated a reduction in body weight in both male and female rats over a period of 90 days as compared to the corresponding control animals. An advancing age-induced marginal increase in hepatic lipid peroxidation was observed in both male and female rats as compared to the corresponding control animals. However, no such difference in hepatic DNA fragmentation and testicular lipid peroxidation and DNA fragmentation was observed. Furthermore, liver and testis weight, expressed as such and as a percentage of body weight and brain weight, at 30, 60 and 90 days of treatment, exhibited no significant difference between the four groups. Taken together, these results indicate that treatment of HCA-SX over a period of 90 days results in a reduction in body weight, but did not cause any changes in hepatic and testicular lipid peroxidation, DNA fragmentation, or histopathological changes.     

Safety and toxicological evaluation of a novel niacin-bound chromium (III) complex

Chromium is an essential trace element required for normal protein, fat and carbohydrate metabolism. It also helps in energy production and increasing lean body mass. Niacin-bound chromium (NBC) is a unique form of bioavailable chromium that promotes healthy lipid profile. This study was focused on determining the broad spectrum safety of NBC. Acute oral, acute dermal, primary dermal irritation and primary eye irritation toxicities of NBC were evaluated. Ames bacterial reverse mutation assay, mouse lymphoma test and a dose-dependent 90-day subchronic toxicity were also conducted. In safety studies, the acute oral LD(50) of NBC was found to be greater then 5000 mg/kg in both male and female Sprague-Dawley rats. No changes in body weight or adverse effects were observed following necropsy. The acute dermal LD(50) of NBC was found to be >2000 mg/kg. The primary skin irritation test was conducted with NBC on New Zealand Albino rabbits. NBC was classified as slightly irritating. The primary eye irritation test was conducted with NBC on rabbits. NBC was classified as practically non-irritating to the eye. NBC did not induce mutagenic effects in the bacterial reverse mutation test in five Salmonella typhimurium strains (TA1535, TA98, TA100, TA97a and TA102), either with or without metabolic activation. Similarly, NBC did not induce mutagenic effects in the mammalian cell gene mutation test in L5178Y mouse lymphoma cells TK (+/-), either with or without metabolic activation. A dose-dependent 90-day subchronic toxicity study demonstrated no significant changes in selected organ weights individually and as percentages of body and brain weights. NBC supplementation did not cause changes in hepatic lipid peroxidation or DNA fragmentation after 30, 60 or 90 days of treatment. Hematology, clinical chemistry and histopathological evaluations did not show any adverse effects in all organs tested. Taken together, the above results indicate a broad spectrum of safety for NBC.     

Long-term safety evaluation of a novel oxygen-coordinated niacin-bound chromium (III) complex

Chromium (III) is an essential micronutrient required for normal protein, fat and carbohydrate metabolism, as well as helps insulin metabolize fat, turn protein into muscle and convert sugar into energy. A broad spectrum of research investigations including in vitro, in vivo and clinical studies demonstrated the beneficial effects of novel oxygen- coordinated niacin-bound chromium (III) complex (NBC) in promoting glucose-insulin sensitivity, lipid profile, cardioprotective ability and lean body mass. This study examined the long-term safety of NBC by orally administering either 0 or 25 ppm or the human equivalency dose of 1000 microg elemental chromium (III) as NBC per day for 52 consecutive weeks to male and female Sprague-Dawley rats. Animals of each group and each gender were sacrificed on 26, 39, or 52 weeks of treatment. Body weight, physical and ocular health, feed and water intake, selected organ weights as such and as a percentage of liver and brain weight, hepatic lipid peroxidation and DNA fragmentation, hematology and clinical chemistry, and histopathological evaluations were conducted. At 26, 39, or 52 weeks of treatment, body weight gain was significantly reduced by 7.7%, 8.1% and 14.9% in male rats, and 5.5%, 11.4% and 9.6% in female rats, respectively, in the NBC treatment groups. No significant changes were observed in hepatic lipid peroxidation and DNA fragmentation, hematology and clinical chemistry, and histopathological evaluation between control and NBC groups at these time points. These findings, thus far, are in agreement with the subchronic studies in terms of the safety of NBC.     

Safety and mechanism of appetite suppression by a novel hydroxycitric acid extract (HCA-SX)

A growing body of evidence demonstrates the efficacy of Garcinia cambogia-derived natural (–)-hydroxycitric acid (HCA) in weight management by curbing appetite and inhibiting body fat biosynthesis. However, the exact mechanism of action of this novel phytopharmaceutical has yet to be fully understood. In a previous study, we showed that in the rat brain cortex a novel HCA extract (HCA-SX, Super CitriMax) increases the release/availability of radiolabeled 5-hydroxytryptamine or serotonin ([³H]-5-HT), a neurotransmitter implicated in the regulation of eating behavior and appetite control. The aim of the present study was 2-fold: (a) to determine the effect of HCA-SX on 5-HT uptake in rat brain cortex in vitro; and (b) to evaluate the safety of HCA-SX in vivo. Isolated rat brain cortex slices were incubated in oxygenated Krebs solution for 20 min and transferred to buffer solutions containing [³H]-5-HT for different time intervals. In some experiments, tissues were exposed to HCA-SX (10 M – 1 mM) and the serotonin receptor reuptake inhibitors (SRRI) fluoxetine (100 M) plus clomipramine (10 M). Uptake of [³H]-5-HT was expressed as d.p.m./mg wet weight. A time-dependent uptake of [³H]-5-HT occurred in cortical slices reaching a maximum at 60 min. HCA-SX, and fluoxetine plus clomipramine inhibited the time-dependent uptake of [³H]-5-HT. At 90 min, HCA-SX (300 M) caused a 20% decrease, whereas fluoxetine plus clomipramine inhibited [³H]-5-HT uptake by 30%. In safety studies, acute oral toxicity, acute dermal toxicity, primary dermal irritation and primary eye irritation, were conducted in animals using various doses of HCA-SX. Results indicate that the LD₅₀ of HCA-SX is greater than 5000 mg/kg when administered once orally via gastric intubation to fasted male and female Albino rats. No gross toxicological findings were observed under the experimental conditions. Taken together, these in vivo toxicological studies demonstrate that HCA-SX is a safe, natural supplement under the conditions it was tested. Furthermore, HCA-SX can inhibit [³H]-5-HT uptake (and also increase 5-HT availability) in isolated rat brain cortical slices in a manner similar to that of SRRIs, and thus may prove beneficial in controlling appetite, as well as treatment of depression, insomnia, migraine headaches and other serotonin-deficient conditions.     

Super CitriMax (HCA-SX) attenuates increases in oxidative stress, inflammation, insulin resistance, and body weight in developing obese Zucker rats

Super CitriMax (HCA-SX) is a novel calcium/potassium salt of (−)-hydroxycitric acid extracted from the dried fruit rind of the plant Garcinia cambogia, and commonly consumed as weight loss dietary supplement. In the present study, we investigated the effect of HCA-SX on inflammation, oxidative stress and insulin resistance in developing obese Zucker rats, an animal model of type II diabetes associated with inflammation and oxidative stress. Male Zucker rats (5-week old) were supplemented with vehicle (control) and HCA-SX in drinking water for 7 weeks. Oxidative stress markers, including malondialdehyde (MDA), protein carbonyl (DNPH), and protein tyrosine nitration (tyr-NO₂) were measured in the liver and kidney tissues using biochemical and immunoblotting techniques. Compared to controls, the levels of MDA, DNPH and tyr-NO₂ were lower in the liver and kidney of HCA-SX-treated animals. Furthermore, the levels of C-reactive protein and interleukin-6, markers of inflammation measured by ELISA, were lower in the plasma of HCA-SX-supplemented animals compared to controls, as were levels of fasting plasma insulin, glucose, and triglycerides. Interestingly, insulin resistance did not develop in HCA-SX-supplemented rats. Food-intake and body weight gain was also lower in rats supplemented with HCA-SX compared to their control counterparts. These results suggest that HCA-SX supplementation in obese Zucker rats reduces food-intake, body weight gain, and also attenuates the increases in inflammation, oxidative stress, and insulin resistance observed in untreated animals. Therefore, HCA-SX may be used as an intervention to overcome obesity-related complications, including inflammation, oxidative stress, and insulin resistance.     

A single therapeutic dose of valproate affects liver carbohydrate, fat, adenylate, amino acid, coenzyme A, and carnitine metabolism in infant mice: possible clinical significance

We have previously reported that chronic valproate administration reduced ketonemia in suckling mice and fasting epileptic children. The present study demonstrates that even a single dose of valproate in the therapeutic range for man caused a prolonged reduction of plasma beta-hydroxybutyrate levels in normal infant mice; the plasma glucose concentration was also significantly lowered. In the livers of these animals, there were extraordinary decreases in levels of free coenzyme A, acetyl CoA and free carnitine. Concomitantly concentrations of acid-soluble fatty acid (short-chain, non-acetyl) coenzyme A esters and of acid-insoluble (long-chain) fatty acid carnitine esters increased. There was evidence for inhibition of the metabolic flux through the Krebs citric acid cycle at those enzyme reactions which require coenzyme A. While valproate doubled liver alanine levels, concentrations of liver aspartate, glutamate and glutamine were reduced. All of the valproate-induced metabolite changes can be explained by the decrease of coenzyme A due to the accumulation of acid-soluble (non-acetyl) coenzyme A esters (presumably valproyl CoA and further metabolites). Decreased coenzyme A would limit the activities of one or more enzymes in the pathway of fatty acid oxidation and the Krebs citric acid cycle. Secondary decreases in acetyl CoA would limit both ketogenesis and gluconeogenesis. Decreased levels of selected hepatic amino acids could reflect their use as alternative fuels. The effect of clinical doses of valproate in infant mice may relate to the valproate-associated syndrome of hepatic failure and Reye-like encephalopathy in some infants and children and suggest a simple screen for those who may be at particular risk.     

Bioefficacy of a novel calcium-potassium salt of (-)-hydroxycitric acid

Obesity is associated with cardiovascular disease, diabetes and certain forms of cancer. Popular strategies on weight loss often fail to address many key factors such as fat mass, muscle density, bone density, water mass, their inter-relationships and impact on energy production, body composition, and overall health and well-being. (−)-Hydroxycitric acid (HCA), a natural plant extract from the dried fruit rind of Garcinia cambogia, has been reported to promote body fat loss in humans without stimulating the central nervous system. The level of effectiveness of G. cambogia extract is typically attributed solely to HCA. However, other components by their presence or absence may significantly contribute to its therapeutic effectiveness. Typically, HCA used in dietary weight loss supplement is bound to calcium, which results in a poorly soluble (<50%) and less bioavailable form. Conversely, the structural characteristics of a novel Ca²⁺/K⁺ bound (−)-HCA salt (HCA-SX or Super CitriMax) make it completely water soluble as well as bioavailable. An efficacious dosage of HCA-SX (4500 mg/day t.i.d.) provides a good source of Ca²⁺ (495 mg, 49.5% of RDI) and K⁺ (720 mg, 15% of RDI). Ca²⁺ ions are involved in weight management by increasing lipid metabolism, enhancing thermogenesis, and increasing bone density. K⁺, on the other hand, increases energy, reduces hypertension, increases muscle strength and regulates arrhythmias. Both Ca and K act as buffers in pH homeostasis. HCA-SX has been shown to increase serotonin availability, reduce appetite, increase fat oxidation, improve blood lipid levels, reduce body weight, and modulate a number of obesity regulatory genes without affecting the mitochondrial and nuclear proteins required for normal biochemical and physiological functions.     

Effects of niacin-bound chromium, Maitake mushroom fraction SX and (–)-hydroxycitric acid on the metabolic syndrome in aged diabetic Zucker fatty rats

Previous studies in our laboratories have demonstrated that niacin-bound chromium (NBC), Maitake mushroom and (–)-hydroxycitric acid (HCA-SX) can ameliorate hypertension, dyslipidemias and diabetes mellitus, and therefore may be useful in weight management. In the present study, we used aged, diabetic Zucker fatty rats (ZFR) (70–75 weeks) in order to determine whether NBC, fraction SX of Maitake mushroom (MSX) and 60% (–)-hydroxycitric acid (HCA-SX) from Garcinia cambogia, alone or in combination, can affect certain aspects of the metabolic syndrome. Syndrome X or metabolic syndrome has been described as a concurrence of disturbed glucose and insulin metabolism, overweight and abdominal fat distribution, mild dyslipidemia, and hypertension, which are associated with subsequent development of type 2 diabetes mellitus and cardiovascular disease. Four groups of eight ZFR were gavaged daily with different supplements. For the initial three weeks, the control group of ZFR received only water, the second group received NBC 40 mcg elemental chromium/day, the third group received MSX 100 mg/day and the last group received HCA-SX 200 mg/day. During weeks 4–6, the doses of each treatment were doubled. The control animals lost approximately 50 g body weight (BW) per rat over 6 weeks of treatment, which is characteristic of these animals in declining health. In contrast, eight ZFR receiving NBC lost approximately 9 g BW per rat, while rats consuming MSX lost 16 g BW per rat. However, ZFR receiving HCA-SX simulated the pattern in the control group because these animals lost approximately 46 g BW per rat. The wide individual variations resulted in a lack of statistical significance among groups. Nevertheless, 75% of the ZFR in the control group lost more than 50 g BW over the 6 weeks duration, whereas none of the ZFR receiving NBC, 25% of the ZFR receiving MSX and 57% of the ZFR receiving HCA-SX lost over 50 g BW over the 6 weeks of the study. ZFR in all 3 treatment groups showed significantly lower blood pressures as compared to control, which seemed to be dose related. The general trend was for renal and liver blood parameters, hepatic and renal lipid peroxidation and DNA fragmentation to improve due to the supplementation of these natural products. Treatment of animals with a combination of these three novel supplements resulted in a lower SBP and maintenance of BW compared to control animals. These results demonstrate that elderly diabetics and even aging individuals might benefit from a similar regimen.     

Trichosanthes dioica Fruit Ameliorates Experimentally Induced Arsenic Toxicity in Male Albino Rats Through the Alleviation of Oxidative Stress

The present work was focused to evaluate the ameliorative property of aqueous extract of Trichosanthes dioica fruit (AQ T. dioica fruit) against arsenic-induced toxicity in male Wistar albino rats. AQ T. dioica fruit was administered orally to rats at 50 and 100 mg/kg body weight for 20 consecutive days prior to oral administration of sodium arsenite (10 mg/kg) for 10 days. Then the rats were sacrificed for the evaluation of body weights, organ weights, hematological profile, serum biochemical profile, and hepatic and renal antioxidative parameters viz. lipid peroxidation, reduced and oxidized glutathione, glutathione-S-transferase, glutathione peroxidase, glutathione reductase, superoxide dismutase, catalase, and DNA fragmentation. Pretreatment with AQ T. dioica fruit at both doses markedly and significantly normalized body weights, organ weights, hematological profiles, and serum biochemical profile in arsenic-treated animals. Further, AQ T. dioica fruit pretreatment significantly modulated all the aforesaid hepatic and renal biochemical perturbations and reduced DNA fragmentation in arsenic-intoxicated rats. Therefore, from the present findings, it can be concluded that T. dioica fruit possessed remarkable value in amelioration of arsenic-induced hepatic and renal toxicity, mediated by alleviation of arsenic-induced oxidative stress by multiple mechanisms in male albino rats.     

Anti-obesity potential of almond (Prunus dulcis) in experimental animals under cafeteria and atherogenic diets

Background & objectivesNatural dietary supplements are progressively getting famous to supplant synthetic substances particularly in chronic morbidities. The aim of this study was to evaluate the anti-obesity potential of almond on the normal, Cafeteria, and Atherogenic diets.Materials and methodsParameters such as change in body weight, body temperature, lipid profile, organ weights, and fat pad weights were assessed. Central Nervous System related studies (Despair Swim test and Elevated Plus maze test) were also performed to comprehend the effect of the diets, and almond on the brain. All of the experimental animals were randomly assigned to one of three diet categoriesregular, cafeteria, or atherogenic, and fed those diets for 40 days. Each diet had the control group, standard drug group and three almond groups (low dose: 50; medium dose: 100 and high dose: 200 mg/kg body weight). Body weight was recorded every alternate day. On 40th day, body temperature was measured. On day 41, lipid parameters, organ weights, fat pad weights and the CNS parameters were evaluated. ANOVA followed by Duncans Multiple Range Test were used for statistical analysis.ResultsTreatment of animals with either a low or high dose of almond as well as a standard herb prevented a rise in body weight significantly (p = 0.01) in all three diet groups. When a regular diet was replaced with a cafeteria and atherogenic diet, the serum levels of triglycerides and LDL increased significantly, while HDL levels decreased significantly. Overall, almond preparation reduced lipid parameters, organ weights, fat-pad weights, and stabilized CNS parameters substantially.Interpretation & conclusionThe almond high dose was the most effective of all the almond preparations. Our study suggests that chronic administration of almond independently reduces the body weight in experimental animals.     

Malnutrition in rats during pregnancy and lactation period: a study on body, spleen and thymus weights and hematologic parameters in dams and their offspring

Physiological changes in the rat dams and their offspring as sequelae of malnutrition during pregnancy and lactation and their capacity for recuperation from early malnutrition is studied. The dams were killed during the lactation period (15th and 30th days of postpartum) and the absolute and relative weights of the thymus and spleen were recorded. The following hematologic parameters were examined: red blood cell count, hemoglobin, hematocrit, mean cell volume, mean cell homoglobin, mean cell hemoglobin concentration, white blood cell count, lymphocytes, monocytes, eosinophils, polimorphonuclear neutrophil, basophils. The offspring were sacrificed at 15, 30 and 90 days of age. Their body weight and the same hematic parameters and organ weights as their mothers were determined. Results indicate a highly significant decrease in body weight and organ weights in experimental dams and an important alteration in their hematic parameters, which may be an important determinant of retardation of growth in pups, whose body and organ weights were significantly smaller than those of the controls. In addition, the hematologic parameters of the malnourished offspring were modified in relation to those of the controls at all times (15, 30 and 90 days old) studied.     

Potential subchronic food safety of the stacked trait transgenic maize GH5112E-117C in Sprague-Dawley rats

The food safety of stacked trait genetically modified (GM) maize GH5112E-117C containing insect-resistance gene Cry1Ah and glyphosate-resistant gene G2-aroA was evaluated in comparison to non-GM Hi-II maize fed to Sprague-Dawley rats during a 90-day subchronic feeding study. Three different dietary concentrations (12.5, 25 and 50 %, w/w) of the GM maize were used or its corresponding non-GM maize. No biologically significant differences in the animals’ clinical signs, body weights, food consumption, hematology, clinical chemistry, organ weights and histopathology were found between the stacked trait GM maize groups, and the non-GM maize groups. The results of the 90-day subchronic feeding study demonstrated that the stacked trait GM maize GH5112E-117C is as safe as the conventional non-GM maize Hi-II.     

Intravenous repeated-dose toxicity study of ZnPcS2P2-based-photodynamic therapy in Wistar rats.

The purpose of the current study was to investigate the potential repeated-dose toxicity of ZnPcP2S2-based photodynamic therapy (ZnPc-PDT) in Wistar rats. The animals were administered ZnPcS2P2 intravenously ten times successively every 4 d and irradiated with a 670 nm laser light for 6 min at subsequent 48 h and 72 h. At the end of the treatment period, 10 rats/sex/group were sacrificed, while 5 rats/sex/group were sacrificed after a two-week recovery period. During the test period, clinical signs, mortality, body weights, food and water consumption, ophthalmoscopy, hematology, serum biochemistry, urinalysis, organ weights, gross findings and histopathology were examined. The association between the increased liver weight and hepatic spotty and lytic necrosis seen in high dose females corroborates the conclusion that high dose ZnPc-PDT could induce hepatic injury in Wistar rats and they are probably related to the abnormality of certain biochemical parameters of females in the high dose group. Furthermore, microscopic examination for the ZnPc-PDT groups shows the presence of some Kelly and khaki granules in Kupffer cells and endothelia of the livers, epithelia of the renal tubules, marginal sinus and medulla of the spleens, alveolar walls of the lungs, reticular cells and macrophages of the mesenteric lymph nodes, testicular Leydig cells, epididymal epithelial cells, endometrial stromal cells, and interstitial cells and corpora lutea of the ovaries from all or most of the animals. There were no adverse effects on mortality, clinical signs, food and water consumption, ophthalmoscopy, uranalysis, hematology, serum biochemistry, body weights and necropsy findings in control, low and mid dose groups. Based on these results, it was concluded that the intravenous repeated-dose of ZnPcP2S2-PDT induced the abnormalities of liver weights, hepatic biochemistry and histopathology, and pigmentation in the several important organs in Wistar rats at 4 mg kg(-1) d(-1). The target organ was determined to be liver (and spleen perhaps), but this was not so obvious in males. The no-observed-adverse-effect level (NOAEL) was considered to be 1.0 mg kg(-1) for both sexes.     

Relationship between acid-soluble carnitine and coenzyme A pools in vivo

The relationship between the acid-soluble carnitine and coenzyme A pools was studied in fed and 24-h-starved rats after carnitine administration. Carnitine given by intravenous injection at a dose of 60μmol/100g body wt. was integrated into the animal's endogenous carnitine pool. Large amounts of acylcarnitines appeared in the plasma and liver within 5min of carnitine injection. Differences in acid-soluble acylcarnitine concentrations were observed between fed and starved rats after injection and reflected the acylcarnitine/carnitine relationship seen in the endogenous carnitine pool of the two metabolic states. Thus, a larger acylcarnitine production was seen in starved animals and indicated a greater source of accessible acyl-CoA molecules. In addition to changes in the amount of acylcarnitines present, the specific acyl groups present also varied between groups of animals. Acetylcarnitine made up 37 and 53% of liver acid-soluble acylcarnitines in uninjected fed and starved animals respectively. At 5min after carnitine injection hepatic acid-soluble acylcarnitines were 41 and 73% in the form of acetylcarnitine in fed and starved rats respectively. Despite these large changes in carnitine and acylcarnitines, no changes were observed in plasma non-esterified fatty acid or β-hydroxybutyrate concentrations in either fed or starved rats. Additionally, measurement of acetyl-CoA, coenzyme A, total acid-soluble CoA and acid-insoluble CoA demonstrated that the hepatic CoA pool was resistant to carnitine-induced changes. This lack of change in the hepatic CoA pool or ketone-body production while acyl groups are shunted from acyl-CoA molecules to acylcarnitines suggests a low flux through the carnitine pool compared with the CoA pool. These results support the concept that the carnitine/acid-soluble acylcarnitine pool reflects changes in, rather than inducing changes in, the hepatic CoA/acyl-CoA pool.     

Inhibition of stearoyl CoA desaturase activity induces hypercholesterolemia in the cholesterol-fed hamster

Reduction of stearoyl CoA desaturase (SCD) activity has been shown to induce resistance to diet-induced obesity in mice. In the present study, SCD was inhibited by feeding sterculic oil (SO) to male Golden Syrian Hamsters fed high-fat diets with or without added dietary cholesterol. In the absence of cholesterol, SO had little impact on adipose tissue mass or plasma lipoprotein concentrations. When cholesterol was included in the diet, inhibition of SCD resulted in reduced body weight, adipose tissue mass, and feed efficiency. These animals also exhibited a marked hypercholesterolemia, with an accumulation of free-cholesterol-rich particles within the LDL density range, and reduced hepatic cholesterol esterification. This was accompanied by a 20-fold increase in plasma alanine aminotransferase, which was suggestive of significant hepatic damage. Hepatic acetyl CoA carboxylase and fatty acid synthase mRNA concentrations were reduced by feeding cholesterol and SO, whereas lipoprotein lipase and SCD mRNA were increased. These changes were associated with decreased hepatic sterol regulatory element binding protein 1a and 1c mRNA concentrations. Thus, inhibition of SCD activity in the cholesterol-fed hamster results in a reduction in overall body weight and adipose tissue deposition. However, this also causes marked hypercholesterolemia and potential liver damage.     

The relationship between organ weights and body weights, facial dimensions, and dental dimensions in a population of olive baboons (Papio cynocephalus anubis)

Questions concerned with the relationship between organ weights and body weight on an intraspecific level are best answered by using a sample of animals collected in the wild from a single locale during a single season. The organ weights and body weights for this study were obtained from the necropsy reports prepared in the field (Athi Plain, Kenya) by H. C. McGill, Jr. on 36 adult animals (18 males and 18 females). Dental and facial measurements were taken by M.I. Siegel. In order to avoid erroneous results produced by statistical treatment of combined sex samples of sexually dimorphic species, data on the sexes were analyzed separately. Means and standard deviations are reported for selected organ weights and body dimensions (heart, lung, liver, spleen, kidney, adrenal, brain, and pancreas weights, crown–rump length, crown–heel length, head circumference, chest circumference, and body weight). All of the above measures were significantly (p<0.05) different between the sexes. Logarithms of these measures were significantly correlated with the logarithm of body weight in males for heart, lung, liver, spleen, kidney, and adrenal weights, crown–heel length, and head and chest circumference, and in females for crown–heel length, heart, liver, and kidney weights. Partial correlational analysis, removing the effects of body size (weight), showed mostly negative correlational relationships between dental and visceral dimensions. Most of the correlations between facial and visceral dimensions were negative. Allometric equations were calculated for the dental, facial, and visceral dimensions versus body weight, and are compared with prior published results.     

Garcinia cambogia extract ameliorates visceral adiposity in C57BL/6J mice fed on a high-fat diet

The aim of present study is to evaluate the effects of Garcinia cambogia on the mRNA levels of the various genes involved in adipogenesis, as well as on body weight gain, visceral fat accumulation, and other biochemical markers of obesity in obesity-prone C57BL/6J mice. Consumption of the Garcinia cambogia extract effectively lowered the body weight gain, visceral fat accumulation, blood and hepatic lipid concentrations, and plasma insulin and leptin levels in a high-fat diet (HFD)-induced obesity mouse model. The Garcinia cambogia extract reversed the HFD-induced changes in the expression pattern of such epididymal adipose tissue genes as adipocyte protein aP2 (aP2), sterol regulatory element-binding factor 1c (SREBP1c), peroxisome proliferator-activated receptor gamma2 (PPARgamma2), and CCAT/enhancer-binding protein alpha (C/EBPalpha). These findings suggest that the Garcinia cambogia extract ameliorated HFD-induced obesity, probably by modulating multiple genes associated with adipogenesis, such as aP2, SREBP1c, PPARgamma2, and C/EBPalpha in the visceral fat tissue of mice.