scholarly journals Arginase II Plays a Central Role in the Sexual Dimorphism of Arginine Metabolism in C57BL/6 Mice

2020 ◽  
Vol 150 (12) ◽  
pp. 3133-3140
Author(s):  
Mahmoud A Mohammad ◽  
Inka C Didelija ◽  
Juan C Marini
Keyword(s):  
Sexual Dimorphism ◽  
Plasma Concentration ◽  
Arginase Activity ◽  
Whole Body ◽  
Synthesis Rate ◽  
Male Mice ◽  
Arginine Metabolism ◽  
Female Mice ◽  
Arginase Ii ◽  
Endogenous Synthesis

ABSTRACT Background Sex differences in plasma concentration of arginine and arginase activity of different tissues have been reported in mice. In addition, male but not female C57BL/6 mice have a dietary arginine requirement for growth. Objective The goal of this research was to test the hypothesis that arginase II is a key factor in the sexual dimorphism of arginine metabolism. Methods Young adult male and female wild type (WT), and heterozygous and arginase II knockout mice on a C57BL/6 background mice were infused with labeled citrulline, arginine, ornithine, phenylalanine, and tyrosine to determine the rates of appearance and interconversion of these amino acids. Tissue arginase activity was measured in the liver, heart, jejunum, kidney, pancreas, and spleen with an arginine radioisotope. The effect of genotype, sex, and their interaction was tested. Results Female mice produced ∼36% more citrulline than their male littermates, which translated into a greater arginine endogenous synthesis, flux, and plasma concentration (42, 6, and 27%, respectively; P < 0.001). Female mice also had a greater phenylalanine flux (10%) indicating a greater rate of whole protein breakdown; however, they had a lower protein synthesis rate than males (18%; P < 0.001). The ablation of arginase II reduced the production of citrulline and the de novo synthesis of arginine in females and increased the rate of appearance of arginine and plasma arginine concentration in male mice (16 and 22%, respectively; P < 0.001). No effect of arginase II deletion, however, was observed for whole-body protein kinetics. Arginase II activity was present in the pancreas, kidney, jejunum, and spleen; WT females had a ∼2-fold greater renal arginase activity than their WT counterparts. Conclusions A clear sexual dimorphism exists in the endogenous synthesis of arginine and its disposal. Female mice have a greater arginine availability than their male littermates. The ablation of arginase II increases arginine availability in male mice.

scholarly journals Gonadal Steroids Negatively Modulate Oxidative Stress in CBA/Ca Female Mice Infected withP. bergheiANKA

2014 ◽  
Vol 2014 ◽  
pp. 1-10 ◽  
Author(s):  
Néstor Aarón Mosqueda-Romo ◽  
Ana Laura Rodríguez-Morales ◽  
Fidel Orlando Buendía-González ◽  
Margarita Aguilar-Sánchez ◽  
Jorge Morales-Montor ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Nitric Oxide ◽  
Superoxide Dismutase ◽  
Sexual Dimorphism ◽  
Stress Response ◽  
Glutathione Peroxidase ◽  
Oxidative Stress Response ◽  
Gonadal Steroids ◽  
Male Mice ◽  
Female Mice

We decreased the level of gonadal steroids in female and male mice by gonadectomy. We infected these mice withP. bergheiANKA and observed the subsequent impact on the oxidative stress response. Intact females developed lower levels of parasitaemia and lost weight faster than intact males. Gonadectomised female mice displayed increased levels of parasitaemia, increased body mass, and increased anaemia compared with their male counterparts. In addition, gonadectomised females exhibited lower specific catalase, superoxide dismutase, and glutathione peroxidase activities in their blood and spleen tissues compared with gonadectomised males. To further study the oxidative stress response inP. bergheiANKA-infected gonadectomised mice, nitric oxide levels were assessed in the blood and spleen, and MDA levels were assessed in the spleen. Intact, sham-operated, and gonadectomised female mice exhibited higher levels of nitric oxide in the blood and spleen compared with male mice. MDA levels were higher in all of the female groups. Finally, gonadectomy significantly increased the oxidative stress levels in females but not in males. These data suggest that differential oxidative stress is influenced by oestrogens that may contribute to sexual dimorphism in malaria.

scholarly journals CTRP12 ablation differentially affects energy expenditure, body weight, and insulin sensitivity in male and female mice

2020 ◽  
Vol 319 (1) ◽  
pp. E146-E162 ◽  
Author(s):  
Stefanie Y. Tan ◽  
Xia Lei ◽  
Hannah C. Little ◽  
Susana Rodriguez ◽  
Dylan C. Sarver ◽  
...  
Keyword(s):  
Body Weight ◽  
Weight Gain ◽  
Insulin Sensitivity ◽  
Energy Expenditure ◽  
Elevated Serum ◽  
Liver Weight ◽  
Homozygous Deletion ◽  
Whole Body ◽  
Male Mice ◽  
Female Mice

Secreted hormones facilitate tissue cross talk to maintain energy balance. We previously described C1q/TNF-related protein 12 (CTRP12) as a novel metabolic hormone. Gain-of-function and partial-deficiency mouse models have highlighted important roles for this fat-derived adipokine in modulating systemic metabolism. Whether CTRP12 is essential and required for metabolic homeostasis is unknown. We show here that homozygous deletion of Ctrp12 gene results in sexually dimorphic phenotypes. Under basal conditions, complete loss of CTRP12 had little impact on male mice, whereas it decreased body weight (driven by reduced lean mass and liver weight) and improved insulin sensitivity in female mice. When challenged with a high-fat diet, Ctrp12 knockout (KO) male mice had decreased energy expenditure, increased weight gain and adiposity, elevated serum TNFα level, and reduced insulin sensitivity. In contrast, female KO mice had reduced weight gain and liver weight. The expression of lipid synthesis and catabolism genes, as well as profibrotic, endoplasmic reticulum stress, and oxidative stress genes were largely unaffected in the adipose tissue of Ctrp12 KO male mice. Despite greater adiposity and insulin resistance, Ctrp12 KO male mice fed an obesogenic diet had lower circulating triglyceride and free fatty acid levels. In contrast, lipid profiles of the leaner female KO mice were not different from those of WT controls. These data suggest that CTRP12 contributes to whole body energy metabolism in genotype-, diet-, and sex-dependent manners, underscoring complex gene-environment interactions influencing metabolic outcomes.

Mouse anococcygeus muscle: sexual dimorphism and responsiveness to sex hormones

1997 ◽  
Vol 152 (2) ◽  
pp. 229-237 ◽  
Author(s):  
Y Fukazawa ◽  
T Iguchi ◽  
H A Bern
Keyword(s):  
Sexual Dimorphism ◽  
Oestrogen Receptor ◽  
Strain Differences ◽  
Neonatal Exposure ◽  
Thin Sheets ◽  
Male Mice ◽  
Cross Sectional ◽  
Female Mice ◽  
Anococcygeus Muscle ◽  
Icr Mice

Abstract The anococcygeus muscle (AcM) is one of a pair of thin sheets of smooth muscle inserting on the rectum, having a tendinous origin largely on sacral vertebrae. The cross-sectional area of AcM in the juxtarectal region in 90-day-old male mice was significantly larger than that in females of three strains: BALB/cCrgl, ICR/Jcl and C57BL/Tw. The AcM area in female mice showed strain differences: BALB/c>ICR>C57BL. Five daily injections of testosterone into newborn ICR mice from the day of birth significantly increased the areas of AcM in both sexes at 30 days of age, but five daily injections of oestradiol-17β (OE) decreased them. The AcM area in 60-day-old ICR male mice castrated at 30 days of age was significantly smaller than in intact males, and that in ovariectomized females was significantly larger than in intact females. In both sexes, implantation of a testosterone pellet (12 mg) into gonadectomized mice on the day of gonadectomy stimulated the growth of AcM, and implantation of an OE pellet (12 mg) inhibited the growth of AcM. The AcM in both ICR and C57BL strains showed positive androgen receptor and oestrogen receptor immunostaining at 15 days. Female ICR mice exposed neonatally to diethylstilboestrol (DES) had significantly larger AcM than controls; ovariectomy at 30 days of age did not change the AcM area in 60-day-old DES-exposed mice. However, male mice exposed neonatally to DES had significantly smaller AcM than controls; castration at 30 days of age nullified this inhibition. These results suggest that both androgen and oestrogen play an important role in sexual dimorphism of the mouse AcM. Neonatal exposure to DES (but not to oestradiol) had an irreversible stimulatory effect on the AcM area in female mice. Journal of Endocrinology (1997) 152, 229–237

Inactive plasma renin exhibits sex difference in mice

1989 ◽  
Vol 76 (4) ◽  
pp. 439-446 ◽  
Author(s):  
Arne Høj Nielsen ◽  
Arne Johannessen ◽  
Knud Poulsen
Keyword(s):  
Plasma Concentration ◽  
Sex Difference ◽  
Plasma Renin ◽  
High Plasma ◽  
Normal Male ◽  
Normal Female ◽  
Male Mice ◽  
Submandibular Glands ◽  
Female Mice ◽  
Inactive Renin

1. The plasma concentration of inactive renin was two-to three-fold higher in male than in female mice independently of whether mice of strains with low (BALB/c) or high (Theiller) content of active renin in the submandibular salivary glands were studied. 2. Removal of the submandibular glands did not affect the high plasma concentration of inactive renin in male mice. 3. Inactive plasma renin decreased over several days after castration of normal and sialoadenectomized male mice to the same levels as those found in normal female mice. 4. Treatment of these castrated male mice with testosterone increased and normalized inactive plasma renin independently of whether the submandibular glands had been previously removed or not. 5. Testosterone treatment of sialoadenectomized female mice increased inactive renin to the same levels as those found in normal male mice. 6. Our findings suggest that the sex difference in inactive plasma renin in mice may be explained by an increased secretion of inactive renin in male mice stimulated by androgens. 7. Since we have recently found that inactive plasma renin in male mice is mainly of renal origin, this increased secretion is most likely located to the kidneys.

scholarly journals Sexual Dimorphism in the Control of Amebic Liver Abscess in a Mouse Model of Disease

2006 ◽  
Vol 74 (1) ◽  
pp. 118-124 ◽  
Author(s):  
Hannelore Lotter ◽  
Thomas Jacobs ◽  
Iris Gaworski ◽  
Egbert Tannich
Keyword(s):  
T Cells ◽  
Sexual Dimorphism ◽  
Liver Abscess ◽  
Cytokine Production ◽  
Experimental Studies ◽  
Nkt Cells ◽  
Amebic Liver Abscess ◽  
Male Mice ◽  
Female Mice ◽  
Ifn Γ

ABSTRACT Amebic liver abscess (ALA) is the most common extraintestinal manifestation of human infection by the enteric protozoan parasite Entamoeba histolytica. In contrast to intestinal infection, ALA greatly predominates in males but is rare in females. Since humans are the only relevant host for E. histolytica, experimental studies concerning this sexual dimorphism have been hampered by the lack of a suitable animal model. By serial liver passage of cultured E. histolytica trophozoites in gerbils and mice, we generated amebae which reproducibly induce ALA in C57BL/6 mice. Interestingly, all animals developed ALA, but the time courses of abscess formation differed significantly between the genders. Female mice were able to clear the infection within 3 days, whereas in male mice the parasite could be recovered for at least 14 days. Accordingly, male mice showed a prolonged time of recovery from ALA. Immunohistology of abscesses revealed that polymorphonuclear leukocytes and macrophages were the dominant infiltrates, but in addition, γ,δ-T cells, NK cells, and natural killer T (NKT) cells were also present at early times during abscess development, whereas conventional α,β-T cells appeared later, when female mice had already cleared the parasite. Interestingly, male and female mice differed in early cytokine production in response to ameba infection. Enzyme-linked immunospot assays performed with spleen cells of infected animals revealed significantly higher numbers of interleukin-4-producing cells in male mice but significantly higher numbers of gamma interferon (IFN-γ)-producing cells in female mice. Early IFN-γ production and the presence of functional NKT cells were found to be important for the control of hepatic amebiasis as application of an IFN-γ-neutralizing monoclonal antibody or the use of NKT knockout mice (Vα14iNKT, Jα 18−/−) dramatically increased the size of ALA in female mice. In addition, E. histolytica trophozoites could be reisolated from liver abscesses of Jα18−/− mice on day 7 postinfection, when wild-type mice had already cleared the parasite. These data suggest that the sexual dimorphism in the control of ALA is due to gender-specific differences in early cytokine production mediated at least in part by NKT cells in response to E. histolytica infection of the liver.

scholarly journals Cytogenetic damage in preimplantation mouse embryos generated after paternal and parental γ-irradiation and the influence of vitamin C

Reproduction ◽  
2009 ◽  
Vol 137 (1) ◽  
pp. 35-43 ◽  
Author(s):  
Hossein Mozdarani ◽  
Elmina Nazari
Keyword(s):  
Vitamin C ◽  
Chromosomal Abnormalities ◽  
Radical Scavenging ◽  
Whole Body ◽  
Preimplantation Embryos ◽  
Control Group ◽  
Male Mice ◽  
Male And Female ◽  
Cytogenetic Damage ◽  
Female Mice

Cytogenetic damage expressed as micronuclei (MN) in 4–8-cell embryos generated after irradiation of male or male and female mice in the absence and presence of vitamin C was investigated. Male NMRI mice were whole body exposed to 4 Gy γ-rays and mated with non-irradiated superovulated female mice in 6 successive weeks after irradiation in a weekly interval. In experiments involving irradiation of both male and female mice, irradiated male mice for 6 weeks post irradiation were mated with female mice irradiated after induction of superovulation. Effect of 100 mg/kg vitamin C (ascorbic acid) on the frequency of MN was also studied. Pregnant animals were euthanized and embryos flushed from the oviducts and fixed on slides. The rate of MN observed in embryos generated from irradiated male compared with control group dramatically increased (P<0.01). Frequency of MN in this group decreased dramatically after vitamin C treatment (P<0.01). Frequency of MN in embryos generated by mating both male and female irradiated mice was higher than that observed for those embryos generated by irradiated male mice alone. However, a considerable modifying effect of vitamin C was observed for this group too (P<0.05). Results indicate that irradiation of gonads during spermatogenesis and preovulatory stage oocytes may lead to unstable chromosomal aberrations and probably stable chromosomal abnormalities affecting pairing and disjunction of chromosomes in successive preimplantation embryos expressed as MN. The way vitamin C reduces clastogenic effects of radiation on germ cells leading to reduced frequency of MN in pre-embryos might be due to its antioxidation and radical scavenging properties.

scholarly journals Partial deficiency of CTRP12 alters hepatic lipid metabolism

2016 ◽  
Vol 48 (12) ◽  
pp. 936-949 ◽  
Author(s):  
Stefanie Y. Tan ◽  
Hannah C. Little ◽  
Xia Lei ◽  
Shuoyang Li ◽  
Susana Rodriguez ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
High Fat Diet ◽  
Whole Body ◽  
Male Mice ◽  
Hepatic Triglyceride ◽  
High Fat ◽  
Low Fat ◽  
Female Mice ◽  
Low Fat Diet ◽  
Triglyceride Secretion

Secreted hormones play pivotal roles in tissue cross talk to maintain physiologic blood glucose and lipid levels. We previously showed that C1q/TNF-related protein 12 (CTRP12) is a novel secreted protein involved in regulating glucose metabolism whose circulating levels are reduced in obese and insulin-resistant mouse models. Its role in lipid metabolism, however, is unknown. Using a novel heterozygous mouse model, we show that the loss of a single copy of the Ctrp12 gene (also known as Fam132a and adipolin) affects whole body lipid metabolism. In Ctrp12 (+/−) male mice fed a control low-fat diet, hepatic fat oxidation was upregulated while hepatic VLDL-triglyceride secretion was reduced relative to wild-type (WT) littermates. When challenged with a high-fat diet, Ctrp12 (+/−) male mice had impaired lipid clearance in response to acute lipid gavage, reduced hepatic triglyceride secretion, and greater steatosis with higher liver triglyceride and cholesterol levels. Unlike male mice, Ctrp12 (+/−) female mice fed a control low-fat diet were indistinguishable from WT littermates. When obesity was induced by high-fat feeding, Ctrp12 (+/−) female mice developed mild insulin resistance with impaired insulin tolerance. In contrast to male mice, hepatic triglyceride secretion was increased in Ctrp12 (+/−) female mice fed a high-fat diet. Thus, in different dietary and metabolic contexts, loss of a single Ctrp12 allele affects glucose and lipid metabolism in a sex-dependent manner, highlighting the importance of genetic and environmental determinants of metabolic phenotypes.

scholarly journals Phenotypic Sexual Dimorphism in Response to Dietary Fat Manipulation in C57BL/6J Mice

2020 ◽  
Author(s):  
Isabel Casimiro ◽  
Natalie D. Stull ◽  
Sarah A. Tersey ◽  
Raghavendra Mirmira
Keyword(s):  
Sexual Dimorphism ◽  
Locomotor Activity ◽  
Glucose Tolerance ◽  
Food Consumption ◽  
High Fat Diet ◽  
Male Mice ◽  
High Fat ◽  
Β Cell ◽  
Male And Female ◽  
Female Mice

Abstract Background:Obesity and the metabolic syndrome are increasingly prevalent in society and their complications and response to treatment exhibit sexual dimorphism. Mouse models of high fat diet-induced obesity are commonly used for both mechanistic and therapeutic studies of metabolic disease and diabetes. However, the inclusion of female mammals in obesity research has not been a common practice, and has resulted in a paucity of data regarding the effect of sex on metabolic parameters and its applicability to humans. Methods:Here we analyzed male and female C57BL/6J mice beginning at 4 weeks of age that were placed on a low-fat diet (LFD, 10% calories from fat), a Western Diet (WD, 45% calories from fat), or a high fat diet (HFD, 60% calories from fat). Assessments of body composition, glucose homeostasis, insulin production, and energy metabolism, as well as histological analyses of pancreata were performed. Results:Both male and female C57BL/6J mice had similar increases in total percent body weight gain with both WD and HFD compared to LFD, however, male mice gained weight earlier upon HFD or WD feeding compared to female mice. Male mice exhibited a decrease in both food consumption and activity with either WD or HFD compared to LFD, whereas female mice did not exhibit any differences in food intake and minimal changes in locomotor activity on any diet. Glucose tolerance tests performed at 4, 12 and 20 weeks of dietary intervention revealed impaired glucose tolerance that was worse in male mice compared to females. Furthermore, male mice exhibited an increase in pancreatic β cell area as well as reduced insulin sensitivity after HFD feeding compared to WD or LFD, whereas female mice did not. Conclusions:Male and female C57BL/6J mice exhibited strikingly different responses in weight, food consumption, locomotor activity, and β cell adaptation upon dietary manipulation, with the latter exhibiting less striking phenotypic changes. We conclude that the nature of these responses emphasizes the need to contextualize studies of obesity pathophysiology and treatment with respect to sex.

scholarly journals Distinct Changes in Gut Microbiota Are Associated with Estradiol-Mediated Protection from Diet-Induced Obesity in Female Mice

Metabolites ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 499
Author(s):  
Kalpana D. Acharya ◽  
Hye L. Noh ◽  
Madeline E. Graham ◽  
Sujin Suk ◽  
Randall H. Friedline ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Energy Homeostasis ◽  
Whole Body ◽  
Glucose Turnover ◽  
Female Mice ◽  
Adult Mice ◽  
Diet Induced Obesity ◽  
Metabolic Dysregulation ◽  
Regulation Of Metabolism ◽  
Junction Protein

A decrease in ovarian estrogens in postmenopausal women increases the risk of weight gain, cardiovascular disease, type 2 diabetes, and chronic inflammation. While it is known that gut microbiota regulates energy homeostasis, it is unclear if gut microbiota is associated with estradiol regulation of metabolism. In this study, we tested if estradiol-mediated protection from high-fat diet (HFD)-induced obesity and metabolic changes are associated with longitudinal alterations in gut microbiota in female mice. Ovariectomized adult mice with vehicle or estradiol (E2) implants were fed chow for two weeks and HFD for four weeks. As reported previously, E2 increased energy expenditure, physical activity, insulin sensitivity, and whole-body glucose turnover. Interestingly, E2 decreased the tight junction protein occludin, suggesting E2 affects gut epithelial integrity. Moreover, E2 increased Akkermansia and decreased Erysipleotrichaceae and Streptococcaceae. Furthermore, Coprobacillus and Lactococcus were positively correlated, while Akkermansia was negatively correlated, with body weight and fat mass. These results suggest that changes in gut epithelial barrier and specific gut microbiota contribute to E2-mediated protection against diet-induced obesity and metabolic dysregulation. These findings provide support for the gut microbiota as a therapeutic target for treating estrogen-dependent metabolic disorders in women.

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