Body Weight In Female Mice Research Articles

Acute oral toxicity of Cannabis sativa L. co-products in mice

Cannabis sativa L. commonly known as ‘Kif’, is a medicinal plant belonging to the Cannabaceae family (Cannabis genus). It is used in traditional folk medicine to treat several diseases. The recent legalization of cannabis use for medicinal, cosmetic, and industrial purpose in Morocco (law 13.21), has enabled us to assess the potential acute toxicity of extract from its female plant co-products in Swiss mice. In this experimentation, 3 different extraction methods (maceration, decoction, and sonication) were used to determine the efficacy of cannabis extracts and investigate their acute toxicity in mice over a period of 14 days. Decoction showed the highest efficacy (19.7%), followed by maceration (16.2%), and finally sonication (5.4%). Regarding the toxicity results of the oral gavage administration dose at 2,000 mg kg-1, there were no recorded deaths and no changes in the internal organs (kidneys and liver) between treated and control groups of both male and female mice. We also found that body weight of female mice treated by decoction and maceration extracts decreased significantly compared to those treated with sonication extract throughout the experimental period, when treated and untreated male mice show no significant changes (p-value < 0.05). Our findings suggest that the LD50 may be greater than 2.000 mg kg-1. Nevertheless, the extracts showed signs of low-level toxicity such as drowsiness, hypoactivity, and tachycardia. Further studies to determine the phytochemical composition of the three extracts of C. sativa and assess the chronic and sub-chronic toxicity should be carried out.

TLR4 in POMC neurons regulates thermogenesis in a sex-dependent manner

The rising prevalence of obesity has become a worldwide health concern. Obesity usually occurs when there is an imbalance between energy intake and energy expenditure. However, energy expenditure consists of several components, including metabolism, physical activity, and thermogenesis. Toll-like receptor 4 (TLR4) is a transmembrane pattern recognition receptor, and it is abundantly expressed in the brain. Here, we showed that pro-opiomelanocortin (POMC)-specific deficiency of TLR4 directly modulates brown adipose tissue thermogenesis and lipid homeostasis in a sex-dependent manner. Deleting TLR4 in POMC neurons is sufficient to increase energy expenditure and thermogenesis resulting in reduced body weight in male mice. POMC neuron is a subpopulation of tyrosine hydroxylase neurons and projects into brown adipose tissue, which regulates the activity of sympathetic nervous system and contributes to thermogenesis in POMC-TLR4-KO male mice. By contrast, deleting TLR4 in POMC neurons decreases energy expenditure and increases body weight in female mice, which affects lipolysis of white adipose tissue (WAT). Mechanistically, TLR4 KO decreases the expression of the adipose triglyceride lipase and lipolytic enzyme hormone-sensitive lipase in WAT in female mice. Furthermore, the function of immune-related signaling pathway in WAT is inhibited because of obesity, which exacerbates the development of obesity reversely. Together, these results demonstrate that TLR4 in POMC neurons regulates thermogenesis and lipid balance in a sex-dependent manner.

Comparison of toxicity between lanthanum oxide nanoparticles and lanthanum chloride

Due to the wide application of rare earth elements, lanthanum (La) is gradually accumulated in our living environment. Lanthanum can enter the body through a variety of routes, which has a series of effects on various systems. As a consequence, the safety of lanthanum deserves our attention. This study aims to compare the toxicity of lanthanum oxide nanoparticles (La2O3 NPs) and lanthanum chloride (LaCl3) and enrich the toxicity evaluation of lanthanum. Therefore, a 30 d intragastal experiment was conducted. C57BL/6j mice were given by La2O3 NPs solution and LaCl3 solution respectively at doses of 0, 30, 60 and 120 mg/kg BW (lanthanum content). The results show that, compared with the control group, both La2O3 NPs and LaCl3 can reduce the body weight of female mice in the high-dose group, but for male mice, the high-dose La2O3 NPs solution can increase the body weight, while LaCl3 has the opposite effect. The coefficients of liver, kidney, heart, lung, uterine and ovaries increase first and then decrease with the exposure dose, but testes and epididymides coefficient keep increasing with the exposure of LaCl3 and La2O3 NPs. La2O3 NPs and LaCl3 can reduce the concentration of triglycerides (TG) and increase the level of low density lipoprotein (LDL), but the effect of La2O3 NPs is more obvious. La2O3 NPs and LaCl3 can reduce the concentration of malondialdehyde (MDA), increase the total antioxidant capacity (T–AOC) and enhance the activity of catalase (CAT), but LaCl3 has more obvious protective effects on oxidative stress. La2O3 NPs and LaCl3 have potential risks to liver, and the toxicity of La2O3 NPs might be higher than that of LaCl3.

Effects of oxytocin and antagonist antidote atosiban on body weight and food intake of female mice, Mus musculus

Growing evidence suggests that oxytocin (OT) plays an important factor for the control of food intake, body weight, and energy metabolism in human and non-human animals. It has reported previously, the downregulation in oxytocin receptors (OTRs) expression is linked with the development of obesity, but exogenous OT reverse body weight and food intake in obese animal model. It is important to know that, whether intraperitoneal administration crosses blood brain barrier. Therefore, in the present experiment, we study the impact of intraperitoneal administration of synthetic OT 0.0116 mg/kg and antagonist atosiban (OTA) 1 mg/kg on food intake, and body weight of female mice, Mus musculus for different duration i.e. 30, 60, and 90 days. In this study, it was observed that there was significant decrease (p<0.001, one-way analysis of variance [ANOVA]) in the body weight (BW), food intake, and gonadosmatic indices (GSI) after the intraperitoneal exposure of OT at dose 0.0116 mg/kg up to 90 days and inhibits via antagonist atosiban. These results indicates that intraperitoneal administration of OT can be used for treatment for longer duration without any side effects and maintains homeostasis in physiologic system regulates body weight and gonadal weight in female mice, which represent an important therapeutic tool for the obesity and metabolic disorder in female.

Sex-Dependent Effects of 7,8-Dihydroxyflavone on Metabolic Health Are Associated with Alterations in the Host Gut Microbiome

7,8-Dihydroxyflavone (DHF) is a naturally occurring flavonoid that has been reported to protect against a variety of pathologies. Chronic administration of DHF prevents high-fat diet (HFD)-induced obesity in female, but not male, mice. However, the mechanisms underlying this sexual dimorphism have not been elucidated. We have discovered that oral DHF supplementation significantly attenuates fat mass, hepatic lipid accumulation, and adipose tissue inflammation in female mice. In contrast, male mice were not protected from adiposity, and had a paradoxical worsening of hepatic lipid accumulation and adipose tissue inflammation upon DHF supplementation. Consistent with these sexually dimorphic effects on body weight and metabolic health, 7,8-DHF induced early and stable remodeling of the female intestinal microbiome. DHF supplementation significantly increased gut microbial diversity, and suppressed potentially detrimental bacteria, particularly Desulfovibrionaceae, which are pro-inflammatory and positively associated with obesity and inflammation. Changes in the female gut microbiome preceded alterations in body weights, and in silico analyses indicated that these early microbial changes were highly predictive of subsequent weight gain in female mice. While some alterations in the intestinal microbiome were also observed in male DHF-supplemented mice, these changes were distinct from those in females and, importantly, were not predictive of subsequent body weight changes in male animals. The temporality of microbial changes preceding alterations in body weight in female mice suggests a role for the gut microbiome in mediating the sexually dimorphic effects of DHF on body weight. Given the significant clinical interest in this flavonoid across a wide range of pathologies, further elucidation of these sexually dimorphic effects will aid the development of effective clinical therapies.

Effects of a high-fat diet on the lipid profile of oocytes in mice

Существуют предпосылки того, что у женщин с ожирением возможно снижение качества ооцитов. При этом остается неясным, как связано это изменение с ожирением: опосредованно или напрямую, че- рез изменение содержания и/или состава липидов в ооцитах. Целью настоящей работы было изучение на мышах влияния богатой жирами диеты, применяемой к самкам-донорам, на качественный состав и общее количество липидов в незрелых и созревших in vivo ооцитах. Установлено, что диета, богатая липидами, при- водит к увеличению массы тела самок мышей по сравнению с контролем ( p < 0.001; 44.77 ± 1.46 и 35.22 ± 1.57 соответственно), а также уровня холестерина ( p < 0.05; 2.06 ± 0.10 и 1.78 ± 0.10 соответственно) и триглицери- дов ( p < 0.05; 2.13 ± 0.23 и 1.49 ± 0.21 соответственно) в крови этих животных. Эта диета не повлияла на степень ненасыщенности внутриклеточных липидов незрелых (0.207 ± 0.004 в эксперименте и 0.206 ± 0.002 в контроле) и зрелых ооцитов (0.212 ± 0.005 в эксперименте и 0.211 ± 0.003 в контроле). При созревании ооцитов in vivo на- блюдалось возрастание содержания внутриклеточных липидов. В зрелых ооцитах количество липидов было больше в экспериментальной группе по сравнению с контролем ( p < 0.01; 8.15 ± 0.37 и 5.83 ± 0.14 соответствен- но). Выявлено увеличение количества внутриклеточных липидов при созревании ооцитов как после стан- дартной диеты ( p < 0.05; 4.72 ± 0.48 и 5.83 ± 0.14 соответственно), так и после диеты, богатой жирами ( p < 0.001; 3.45 ± 0.62 и 8.15 ± 0.37 соответственно). Таким образом, при созревании ооцитов мышей in vivo возрастает со- держание внутриклеточных липидов, богатая жирами диета приводит к повышенному содержанию липидов в зрелых ооцитах.

ACETAZOLAMIDE INCREASES LOCOMOTION, EXPLORATORY BEHAVIOR, AND WEIGHT LOSS FOLLOWING SOCIAL STRESS: A TREATMENT FOR EMOTIONAL EATING?

BackgroundAmphetamines and sympathomimetics (e.g. phenylpropanolamine and ephedrine) are effective, centrally acting drugs that induce weight loss through their potent anorexic and locomotor properties. We first reported that amphetamines and these sympathomimetic agents antagonize catecholamine‐dependent, alpha‐2 adrenergic receptor‐dependent signal transduction mediated by chloride/bicarbonate transport.HypothesisOther drugs that target and inhibit cellular bicarbonate/chloride antiport would similarly demonstrate anorectic properties, induce locomotion, and diminish weight gain ‐‐especially in disorders such as depression or social isolation where there is an increase in emotional eating.MethodsMale and female inbred mice were housed in groups or they underwent the stress of living in social isolation or in solitary metabolic chambers for five days. Mice consumed either normal rodent chow or a rodent food supplemented with high fat, high fructose corn syrup; water was provided ad libitum. To inhibit chloride/bicarbonate transport, acetazolamide (ACT, 3 mM) or vehicle was added to the drinking water. There were no noticeable adverse effects in mice receiving ACT. Following a period of habituation, rodents underwent evaluations of exploratory locomotion and learning with the object recognition test. Food intake and weights were also tracked; for all groups, n ≥ 9.ResultsCompared to the control, unstressed, group housed rodents, living in social isolation reduced spontaneous exploration time in male mice (values expressed as means in sec ± SEM) from 23 ± 4 to 14 ± 3 (p&lt;0.001), and in female mice, from 47 ± 6 to 23 ± 3 (p&lt;0.001). Drinking water supplemented with ACT had no effect on exploration time in group housed mice, but ACT completely restored the diminished exploration time found in mice stressed by isolation to control, grouped mice values. The ratio of time spent exploring new objects compared to familiar items (DR ratio) was also reduced following social isolation from 2.6 ± 0.5 to 1.2 ± 0.2 (p&lt;0.001). ACT completely normalized the DR ratio of the stressed mice. The body weight of female mice fed high fat, high fructose corn syrup diets for 12 weeks and given ACT was significantly reduced when compared to mice drinking only water (weight in g ± SEM), 23.7 + 0.8 v. 21.0 + 0.5, p=0.02. This difference in weight was not due to changes in body water volume, but instead, due to the significant decrease in food consumption and greater locomotor activity recorded in mice fed the ACT.ConclusionDrugs that inhibit chloride/bicarbonate transport could offer a safe, new approach to achieving behavioral weight loss in obese individuals with emotional eating.Support or Funding InformationUniversity of MissouriThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

In vitro membrane damage induced by half-fin anchovy hydrolysates/glucose Maillard reaction products and the effects on oxidative status in vivo.

Membrane damage via the Maillard reaction products of half-fin anchovy hydrolysates and glucose (designated as HAHp(9.0)-G MRPs) was evaluated using an in vitro Escherichia coli (E. coli) model. The incubation of HAHp(9.0)-G MRPs led to a significant increase in outer and inner membrane permeability. Furthermore, membrane integrity was seriously destroyed, as observed by scanning electron microscopy and indicated by the decreased fluorescence signal of 4',6-diamidino-2-phenylindole stain. Interestingly, HAHp(9.0)-G MRPs induced significant hydrogen peroxide (H2O2) production in E. coli after 3 h of incubation, which contributed to the antibacterial activity of HAHp(9.0)-G MRPs. As one of the reactive oxygen species, excess H2O2in vivo might impair the antioxidant balance. Therefore, the oxidative status of healthy mice after short-term intake of HAHp(9.0)-G MRPs was investigated. After the administration of HAHp(9.0)-G MRPs at low dose (0.1 g per kg per day body weight) and high dose (1.0 g per kg per day body weight) for 14 days, the body weight of female mice decreased, and the body weight of male mice increased. However, the administration of HAHp(9.0)-G MRPs did not affect the hepatic antioxidant defense in either female or male mice. Some positive responses, like increased superoxide dismutase (SOD) and glutathione peroxidase (GPx) as well as decreased lipid peroxidation (LPO) content, were detected, especially in liver. Though the decrease in catalase activity indicated that the glycation compounds from HAHp(9.0)-G MRPs might be absorbed in vivo, the lower SOD/GPx ratios of HAHp(9.0)-G MRPs-fed groups than those of the normal groups also suggested that the administration of HAHp(9.0)-G MRPs could reduce LPO stress in mice. Our results suggest that a higher antioxidant status could be generated in the healthy animals after fed with HAHp(9.0)-G MRPs for 14 days.

Abstract P213: Metabolic and Cardiovascular Effects of Melanocortin-4 Receptors in Leptin Receptor-expressing Neurons

Studies in both humans and rodents have clearly established a role for melanocortin-4 receptor (MC4R) in energy homeostasis, sympathetic and cardiovascular function. Both MC4R-deficient humans and rodents develop severe obesity while keeping the sympathetic tone and blood pressure below or within the normal range, indicating that MC4R is required for obesity-associated sympathetic overdrive and hypertension. Indeed, sympathetic overdrive and cardiovascular side effect have been a major problem in developing anti-obesity drugs that target MC4R. Thus, better understanding the neural substrates that mediate distinct metabolic and sympathetic actions of MC4R is needed to provide a more specific target to treat obesity and associated hypertension. We have recently mapped the pattern of co-expression of MC4R and leptin receptor (LepR) and found that, throughout entire mouse brain, these two metabolically important receptors are uniquely co-expressed only in neurons of two brain regions, including the lateral hypothalamic area (LHA) and the periaqueductal gray (PAG). To specifically test the role of MC4R in LepR-expressing neurons, we generated mice with MC4R expression only in LepR-positive neurons by breeding Cre-dependently “reactivatable” MC4R-null mice (MC4R-TB) to LepR-Cre mice. We found that specific re-expression of MC4Rs only in LepR-positive neurons partially suppresses body weight gain especially in female mice (MC4R-TB 31.73 ± 2.2g vs. MC4R-TB::LepR-Cre 27.97 ± 1.8 g, p=0.0013). Direct multi-fiber recording of renal nerve activity (RSNA), however, revealed that neither baseline activity nor MC4R agonist-induced RSNA is significantly altered by restoration of MC4R signaling in LepR-positive neurons (change of RSNA in MC4R-TB 8.844 ± 3.05 vs. MC4R-TB::LepR-Cre 11.95 ± 2.7, p&gt;0.05). Our results suggest that MC4R signaling in leptin-responsive neurons is sufficient to suppress body weight in female mice, but seemingly has no effect on sympathetic traffic to the kidney. Further investigation of the effect of MC4Rs in LepR-positive neurons on blood pressure regulation is underway.

Abstract 79: Sex-dependent Role of Macrophage-derived Insulin-like Growth Factor-1 in Body Growth, Cardiac Homeostasis and Responses to Cardiac Tissue Stress

Biological sex is a key factor influencing the development and progression of cardiovascular disease. While sexual dimorphism has been identified in cardiac physiology and sex-based differences are observed in clinical contexts, the molecular and cellular bases for these differences are not understood. Recently, we found for the first time that female and male hearts are different in their cellular composition. Female hearts comprise significantly greater numbers of resident mesenchymal cells, including cardiac fibroblasts, compared to male hearts, and female hearts consist of differing proportions of multiple leukocyte subsets. We found that these differences are regulated by gonadal hormones. Extending on our previous work, this study investigates sexual dimorphism in cell-specific IGF-1 production and its impact on cardiac inflammatory responses. IGF-1 is a growth factor that is essential for development and injury responses, and that has been previously shown to function in a sex-dependent manner. Using genetic, transcriptomic and high-dimensional flow cytometry approaches, we found that macrophages and fibroblasts are the principle IGF-1 producing cells in the heart, with macrophages from female mouse hearts producing twice as much IGF-1 as in males. This contributed to a ~20% greater level of IGF-1 found in the hearts of females compared to males. Furthermore, constitutive genetic ablation of macrophage-derived IGF-1 resulted in ~30% reduction in total IGF-1 in hearts of female mice, whereas no reduction was observed in male hearts. Surprisingly, we also found that ablation of macrophage-derived IGF-1 reduces body weight in female mice by ~10%. Finally, we found that macrophage-derived IGF-1 regulates cardiac inflammatory responses in a sex-dependent manner. To our knowledge, this is the first study to demonstrate that a macrophage-derived growth factor is essential for normal body growth and plays a sex-dependent role in cardiac inflammatory responses. Our observations provide a cellular and molecular basis for the sexual dimorphism observed in cardiac physiology and pathology, and underscore the importance of considering biological sex in experimental models of cardiac development and disease.

Rcan2 and estradiol independently regulate body weight in female mice

Rcan2 increases food intake and plays an important role in the development of age- and diet- induced obesity in male mice. However, in females, wild-type mice grow almost at a similar rate as Rcan2−/− mice on normal chow diet from 6 weeks of age. Here we showed that the ability of Rcan2 to promote weight gain was attenuated by energy expenditure mediated by 17β-estradiol in female mice. Using ovariectomy-operated models, we found that 17β-estradiol deprivation did not alter food intake, but induced more weight gain in wild-type mice than Rcan2−/− mice. If wild-type mice ingested equally as Rcan2−/− mice, in the same ovarian state they exhibited similar weight changes, but the mice in ovariectomized groups were significantly heavier than the ovarian-intact mice, suggesting that body weight is not only regulated by Rcan2, but also by 17β-estradiol. Furthermore, we demonstrated that Rcan2 and 17β-estradiol independently regulated body weight even on high-fat diets. Therefore, our findings indicate that Rcan2 and 17β-estradiol regulate body weight through different mechanisms. Rcan2 increases food intake, whereas 17β-estradiol promotes energy expenditure. These findings provide novel insights into the sexual dimorphism of body weight regulation.

Sex-Dependent Effects of HO-1 Deletion from Adipocytes in Mice

Induction of heme oxygenase-1 (HO-1) has been demonstrated to decrease body weight and improve insulin sensitivity in several models of obesity in rodents. To further study the role of HO-1 in adipose tissue, we created an adipose-specific HO-1 knockout mouse model. Male and female mice were fed either a control or a high-fat diet for 30 weeks. Body weights were measured weekly and body composition, fasting blood glucose and insulin levels were determined every six weeks. Adipocyte-specific knockout of HO-1 had no significant effect on body weight in mice fed a high-fat diet but increased body weight in female mice fed a normal-fat diet. Although body weights were not different in females fed a high fat diet, loss of HO-1 in adipocytes resulted in significant alterations in body composition. Adipose-specific HO-1 knockout resulted in increased fasting hyperglycemia and insulinemia in female but not male mice on both diets. Adipose-specific knockout of HO-1 resulted in a significant loss of HO activity and a decrease in the protein levels of adiponectin in adipose tissue. These results demonstrate that loss of HO-1 in adipocytes has greater effects on body fat and fasting hyperglycemia in a sex-dependent fashion and that expression of HO-1 in adipose tissue may have a greater protective role in females as compared to males.

Loss of UCP1 exacerbates Western diet-induced glycemic dysregulation independent of changes in body weight in female mice.

We tested the hypothesis that female mice null for uncoupling protein 1 (UCP1) would have increased susceptibility to Western diet-induced "whitening" of brown adipose tissue (AT) and glucose intolerance. Six-week-old C57BL/6J wild-type (WT) and UCP1 knockout (UCP1-/-) mice, housed at 25°C, were randomized to either a control diet (10% kcal from fat) or Western diet (45% kcal from fat and 1% cholesterol) for 28 wk. Loss of UCP1 had no effect on energy intake, energy expenditure, spontaneous physical activity, weight gain, or visceral white AT mass. Despite similar susceptibility to weight gain compared with WT, UCP1-/- exhibited whitening of brown AT evidenced by a striking ~500% increase in mass and appearance of large unilocular adipocytes, increased expression of genes related to inflammation, immune cell infiltration, and endoplasmic reticulum/oxidative stress (P < 0.05), and decreased mitochondrial subunit protein (COX I, II, III, and IV, P < 0.05), all of which were exacerbated by Western diet (P < 0.05). UCP1-/- mice also developed liver steatosis and glucose intolerance, which was worsened by Western diet. Collectively, these findings demonstrate that loss of UCP1 exacerbates Western diet-induced whitening of brown AT, glucose intolerance, and induces liver steatosis. Notably, the adverse metabolic manifestations of UCP1-/- were independent of changes in body weight, visceral adiposity, and energy expenditure. These novel findings uncover a previously unrecognized metabolic protective role of UCP1 that is independent of its already established role in energy homeostasis.

AgRP Neuron-Specific Deletion of Glucocorticoid Receptor Leads to Increased Energy Expenditure and Decreased Body Weight in Female Mice on a High-Fat Diet.

Agouti-related protein (AgRP) expressed in the arcuate nucleus is a potent orexigenic neuropeptide, which increases food intake and reduces energy expenditure resulting in increases in body weight (BW). Glucocorticoids, key hormones that regulate energy balance, have been shown in rodents to regulate the expression of AgRP. In this study, we generated AgRP-specific glucocorticoid receptor (GR)-deficient (knockout [KO]) mice. Female and male KO mice on a high-fat diet (HFD) showed decreases in BW at the age of 6 weeks compared with wild-type mice, and the differences remained significant until 16 weeks old. The degree of resistance to diet-induced obesity was more robust in female than in male mice. On a chow diet, the female KO mice showed slightly but significantly attenuated weight gain compared with wild-type mice after 11 weeks, whereas there were no significant differences in BW in males between genotypes. Visceral fat pad mass was significantly decreased in female KO mice on HFD, whereas there were no significant differences in lean body mass between genotypes. Although food intake was similar between genotypes, oxygen consumption was significantly increased in female KO mice on HFD. In addition, the uncoupling protein-1 expression in the brown adipose tissues was increased in KO mice. These data demonstrate that the absence of GR signaling in AgRP neurons resulted in increases in energy expenditure accompanied by decreases in adiposity in mice fed HFD, indicating that GR signaling in AgRP neurons suppresses energy expenditure under HFD conditions.

Administration of Saccharin to Neonatal Mice Influences Body Composition of Adult Males and Reduces Body Weight of Females

Nutritional or pharmacological perturbations during perinatal growth can cause persistent effects on the function of white adipose tissue, altering susceptibility to obesity later in life. Previous studies have established that saccharin, a nonnutritive sweetener, inhibits lipolysis in mature adipocytes and stimulates adipogenesis. Thus, the current study tested whether neonatal exposure to saccharin via maternal lactation increased susceptibility of mice to diet-induced obesity. Saccharin decreased body weight of female mice beginning postnatal week 3. Decreased liver weights on week 14 corroborated this diminished body weight. Initially, saccharin also reduced male mouse body weight. By week 5, weights transiently rebounded above controls, and by week 14, male body weights did not differ. Body composition analysis revealed that saccharin increased lean and decreased fat mass of male mice, the latter due to decreased adipocyte size and epididymal, perirenal, and sc adipose weights. A mild improvement in glucose tolerance without a change in insulin sensitivity or secretion aligned with this leaner phenotype. Interestingly, microcomputed tomography analysis indicated that saccharin also increased cortical and trabecular bone mass of male mice and modified cortical bone alone in female mice. A modest increase in circulating testosterone may contribute to the leaner phenotype in male mice. Accordingly, the current study established a developmental period in which saccharin at high concentrations reduces adiposity and increases lean and bone mass in male mice while decreasing generalized growth in female mice.

Biochemical and histopathological effects on liver due to acute oral toxicity of aqueous leaf extract of Ecliptaalba on female Swiss albino mice

Background:Limited data is available about the toxicity of herbal remedies used for self-medication. Since a popular medicinal plant Ecliptaalba contains various bioactive molecules, the present study aimed to observe the biochemical and histological changes in liver associated with acute oral toxicity (LD50) of aqueous extract of E. alba (L.) Hassk. in female Swiss albino mice.Materials and Methods:For the acute oral toxicity study, the animals were divided into six groups of 6 mice each. Group– I was normal control and the treatment groups were administered aqueous leaf extract of E. alba orally at different doses of 500 mg (group – I),1750 mg (group–III), 2000 mg (group- IV), 2500 mg (group- V) and 3000 mg/ kg/b.wt.(group- VI) for seven consecutive days. The mice were sacrificed on the eighth day and blood was collected for the analysis of ALP (alkaline phosphatase), SGPT (serum glutamic pyruvic transferase), total protein and albumin. The liver was dissected, weighed, and processed for histopathological analysis.Results:The LD50 was found to be 2316.626 mg/kg /body weight in female mice. Serum SGPT, total protein and albumin increased in treated group- IV (P < 0.05), V (P < 0.01), and VI (P < 0.01) as compared to the control (group- I). ALP level significantly decreased in the treated group- IV (P < 0.05), V (P < 0.01) and VI (P < 0.01). Histopathological changes were observed at dose of 2000 mg (group- IV), 2500 mg (group- V) and 3000 mg (group- VI).Conclusion:It was concluded that oral administration of aqueous leaf extract of E. alba had detrimental effects on biochemical parameters and induced histopathological alterations in liver of female Swiss albino mice at doses higher than 2000 mg/kg/day indicating that its indiscriminate use should be avoided.

ApoA-1 mimetic restores adiponectin expression and insulin sensitivity independent of changes in body weight in female obese mice

Background:We examined the ability of the apolipoprotein AI mimetic peptide L-4F to improve the metabolic state of female and male ob mice and the mechanisms involved.Methods:Female and male lean and obese (ob) mice were administered L-4F or vehicle for 6 weeks. Body weight was measured weekly. Fat distribution, serum cytokines and markers of cardiovascular dysfunction were determined at the end of treatment.Results:L-4F significantly decreased serum interleukin (IL)-6, tumor necrosis factor-α and IL-1β. L-4F improved vascular function, and increased serum adiponectin levels and insulin sensitivity compared with untreated mice. In addition, L-4F treatment increased heme oxygenase (HO)-1, pAKT and pAMPK levels in kidneys of ob animals. pAKT and pAMPK levels were significantly reduced in the presence of an HO inhibitor. Interestingly, L4F did not alter body weight in female mice, but caused a significant reduction in males.Conclusions:L-4F treatments reduced cardiovascular risk factors and improved insulin sensitivity in female ob mice independent of body fat changes. Reduced inflammatory cytokine levels accompanied by increased HO activity, serum adiponectin and improved insulin sensitivity suggest that L-4F may promote the conversion of visceral fat to a healthier phenotype. Therefore, L-4F appears to be a promising therapeutic strategy for treating both cardiovascular risk factors and insulin resistance in obese patients of either gender.

Efficient Expression of Bioactive Human Leptin in Escherichia coli in Soluble Fusion Form

Leptin, a 16kDa nonglycosylated hormone, is produced by mature adipocytes and functions primarily in the hypothalamus to reduce food intake and body weight. To explore a new approach for high-level expression of human Leptin in Escherichia coli, the human Leptin gene, synthesized according to the published sequence, was cloned into the vector pET32a to construct a fusion expression plasmid: Trx-Leptin/pET32a. Our data showed that more than 40% of the fusion protein Trx-Leptin was expressed in soluble form. After purified by Ni-IDA affinity chromatography, cleaved by enterokinase and applied Ni-IDA affinity chromatography again, purified Leptin with homogeneity over 96% was achieved. The bio-functional experiments of purified Leptin showed a significant reduction in food intake and body weight of female mice treated with Leptin by comparing with control mice, and it indicated that the purified Leptin has full biological activity. In addition, our expression system was a very low-cost and efficient prokaryotic expression system. So taken together, our results demonstrated that our expression system of bio-active Leptin provided a new method for producing Leptin in big scale and would be widely applied in commercial Leptin producing industries.

Reduced coenzyme Q10 supplementation decelerates senescence in SAMP1 mice

The SAMP1 strain is a mouse model for accelerated senescence and severe senile amyloidosis. We determined whether supplementation with coenzyme Q10 (CoQ10) could decelerate aging in SAMP1 mice and its potential role in aging. Plasma concentrations of CoQ10 and CoQ9 decreased with age in SAMP1 but not in SAMR1 mice. Supplementation with reduced CoQ10 (CoQH 2, 250 mg/kg/day) for one week increased plasma CoQ10 concentrations, with an accompanying decrease in plasma CoQ9 concentrations. In two series of experiments, lifelong supplementation with CoQH 2 decreased the senescence grading scores from 10 to 14 months, 7 to 15 months, and at 17 months of age. The body weight of female mice increased from 2 to 10 months of age versus controls in the second series of experiments. Lifelong CoQH 2 supplementation did not prolong or shorten the lifespan, nor did it alter the murine senile amyloid (AApoAII) deposition rate or cancer incidence. In the second series of experiments, urinary levels of 8-hydroxydeoxyguanosine did not change with age or long-term supplementation with CoQH 2.Urinary levels of acrolein (ACR)-lysine adduct increased significantly with age in SAMP1 mice; however, CoQH 2 had no effect. Thus, lifelong dietary supplementation with CoQH 2 decreased the degree of senescence in middle-aged SAMP1 mice.

Antipsychotic drug-induced weight gain: development of an animal model

Weight gain is a prominent effect of most atypical antipsychotic drugs (AAPDs); yet, the mechanisms are not fully understood and no well-established mouse models exist for investigating the mechanisms. Thus, we developed a mouse model to evaluate the effects of AAPDs on eating, body weight (BW), and body composition. Female C57BL/6J mice were used to test olanzapine, quetiapine, ziprasidone, and risperidone. Mice were acclimated to individual housing, given ad libitum access to chow and water, dosed with placebo peanut butter pills for 1 week, and then dosed daily with AAPD-laced peanut butter pills for 4 weeks. Weekly food intakes and BWs were measured, and body compositions were determined at the end of each experiment. After 4 weeks of treatment, olanzapine, quetiapine, ziprasidone, and risperidone caused significant weight increases, but only olanzapine and quetiapine were associated with significantly increased food intake. Body composition data revealed that olanzapine-treated mice had more relative fat mass and risperidone-treated mice had more relative lean mass than did control mice. Quetiapine and ziprasidone did not significantly affect relative body composition even though BW was increased. Oral AAPD administration causes increased BW in female mice. Our mouse model of AAPD-induced weight gain resembles the human response to these medications and will be used to investigate the mechanisms for weight gain and fat accumulation.