Obesity and metabolic syndrome induce hyperfiltration, glomerulomegaly, and albuminuria in obese ovariectomized female mice and obese male mice

Menopause ◽  
2021 ◽  
Vol Publish Ahead of Print ◽  
Author(s):  
Ana Elena Rodríguez-Rodríguez ◽  
Javier Donate-Correa ◽  
Sergio Luis-Lima ◽  
Laura Díaz-Martín ◽  
Covadonga Rodríguez-González ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Male Mice ◽  
Female Mice ◽  
Obese Male

scholarly journals Obesity alters Ace2 and Tmprss2 expression in lung, trachea, and esophagus in a sex-dependent manner: Implications for COVID-19

2020 ◽  
Author(s):  
Dylan C. Sarver ◽  
G. William Wong
Keyword(s):  
Respiratory Tract ◽  
Lower Respiratory Tract ◽  
Cell Receptor ◽  
Dependent Manner ◽  
Male Mice ◽  
Female Mice ◽  
Obese Female ◽  
Underlying Basis ◽  
Transmembrane Serine Protease ◽  
Obese Male

ABSTRACTObesity is a major risk factor for SARS-CoV-2 infection and COVID-19 severity. The underlying basis of this association is likely complex in nature. The host-cell receptor angiotensin converting enzyme 2 (ACE2) and the type II transmembrane serine protease (TMPRSS2) are important for viral cell entry. It is unclear whether obesity alters expression of Ace2 and Tmprss2 in the lower respiratory tract. Here, we show that: 1) Ace2 expression is elevated in the lung and trachea of diet-induced obese male mice and reduced in the esophagus of obese female mice relative to lean controls; 2) Tmprss2 expression is increased in the trachea of obese male mice but reduced in the lung and elevated in the trachea of obese female mice relative to lean controls; 3) in chow-fed lean mice, females have higher expression of Ace2 in the lung and esophagus as well as higher Tmprss2 expression in the lung but lower expression in the trachea compared to males; and 4) in diet-induced obese mice, males have higher expression of Ace2 in the trachea and higher expression of Tmprss2 in the lung compared to females, whereas females have higher expression of Tmprss2 in the trachea relative to males. Our data indicate diet- and sex-dependent modulation of Ace2 and Tmprss2 expression in the lower respiratory tract and esophagus. Given the high prevalence of obesity worldwide and a sex-biased mortality rate, we discuss the implications and relevance of our results for COVID-19.

scholarly journals Differences in acidosis-stimulated renal ammonia metabolism in the male and female kidney

2019 ◽  
Vol 317 (4) ◽  
pp. F890-F905 ◽  
Author(s):  
Autumn N. Harris ◽  
Hyun-Wook Lee ◽  
Lijuan Fang ◽  
Jill W. Verlander ◽  
I. David Weiner
Keyword(s):  
Phosphoenolpyruvate Carboxykinase ◽  
Collecting Duct ◽  
Ammonia Excretion ◽  
Volume Density ◽  
Male Mice ◽  
Ammonia Metabolism ◽  
Female Mice ◽  
Predominant Component ◽  
Acid Load ◽  
Acid Loading

Renal ammonia excretion is a critical component of acid-base homeostasis, and changes in ammonia excretion are the predominant component of increased net acid excretion in response to metabolic acidosis. We recently reported substantial sex-dependent differences in basal ammonia metabolism that correlate with sex-dependent differences in renal structure and expression of key proteins involved in ammonia metabolism. The purpose of the present study was to investigate the effect of sex on the renal ammonia response to an exogenous acid load. We studied 4-mo-old C57BL/6 mice. Ammonia excretion, which was less in male mice under basal conditions, increased in response to acid loading to a greater extent in male mice, such that maximal ammonia excretion did not differ between the sexes. Fundamental structural sex differences in the nonacid-loaded kidney persisted after acid loading, with less cortical proximal tubule volume density in the female kidney than in the male kidney, whereas collecting duct volume density was greater in the female kidney. To further investigate sex-dependent differences in the response to acid loading, we examined the expression of proteins involved in ammonia metabolism. The change in expression of phosphoenolpyruvate carboxykinase and Rh family B glycoprotein with acid loading was greater in male mice than in female mice, whereas Na+-K+-2Cl– cotransporter and inner stripe of the outer medulla intercalated cell Rh family C glycoprotein expression were significantly greater in female mice than in male mice. There was no significant sex difference in glutamine synthetase, Na+/H+ exchanger isoform 3, or electrogenic Na+-bicarbonate cotransporter 1 variant A protein expression in response to acid loading. We conclude that substantial sex-dependent differences in the renal ammonia response to acid loading enable a similar maximum ammonia excretion response.

THE EFFECTS OF SPECIES, STRAIN AND SEX IN THYMOLYTIC TESTS OF BETAMETHASONE, DEXAMETHASONE AND OTHER STEROIDS

1962 ◽  
Vol 25 (1) ◽  
pp. 77-85 ◽  
Author(s):  
R. M. ATKINSON ◽  
M. A. PRATT ◽  
E. G. TOMICH
Keyword(s):  
Route Of Administration ◽  
Relative Potency ◽  
Male Mice ◽  
Female Mice ◽  
Betamethasone And Dexamethasone

SUMMARY Cortisol, prednisolone phosphate and the free alcohols and 21-phosphates of betamethasone and dexamethasone have been compared for thymolytic activity by the oral and subcutaneous routes in both sexes of two strains of rats and two strains of mice. The relative potency of betamethasone and dexamethasone differed with the route of administration and the sex, strain and species of animal employed. In female mice of the A2G strain, betamethasone was as potent as dexamethasone; in male mice of this strain, and in both sexes of GFF mice, WAG rats and PVG rats, betamethasone was much less potent than dexamethasone.

Abstract P199: Mas Receptor Deficiency Regulates Obesity-Hypertension and Cardiac Function in Female and Male Mice

Hypertension ◽  
2016 ◽  
Vol 68 (suppl_1) ◽  
Author(s):  
Robin C Shoemaker ◽  
Yu Wang ◽  
Sean Thatcher ◽  
Lisa Cassis
Keyword(s):  
Blood Pressure ◽  
Sexual Dimorphism ◽  
Cardiac Function ◽  
Male Mice ◽  
Reduced Ejection Fraction ◽  
Obesity Hypertension ◽  
Obese Male ◽  
Deficient Mice ◽  
Cmr Imaging

Angiotensin-1-7 (Ang-(1-7)) counteracts angiotensin II through effects at Mas receptors (MasR). We demonstrated that sexual dimorphism of obesity-hypertension was associated with dysregulated production of Ang-(1-7). However, the role of MasR in sexual dimorphism of obesity-hypertension has not been examined. MasR deficient mice have also been reported to exhibit deficits in cardiac function. In this study, we hypothesized that deficiency of the MasR would differentially regulate obesity-hypertension in male versus ( vs ) female mice. In addition, we quantified effects of MasR deficiency on cardiac function in obese male mice. Male and female MasR +/+ and -/- mice were fed a low fat (LF, 10%kcal) or high fat (HF, 60% kcal) diet for 16 weeks, and blood pressure was quantified by radiotelemetry. As demonstrated previously, male MasR +/+ mice (24 hr diastolic blood pressure, DBP: LF, 90 ± 3; HF, 96 ± 2 mmHg; P<0.05), but not females (LF, 85 ± 1; HF, 85 ± 2 mmHg), developed hypertension in response to HF feeding. MasR deficiency converted female HF-fed mice to an obesity-hypertension phenotype (DBP: 92 ± 1 mmHg; P<0.05). Surprisingly, male HF-fed MasR -/- mice exhibited reduced DBP compared to HF-fed MasR +/+ males (90 ± 1 vs 96 ± 2 mmHg; P<0.05). To define mechanisms for reductions in DBP of HF-fed male MasR -/- mice, we performed cardiac magnetic resonance (CMR) imaging in both genotypes at 1 month of HF feeding. MasR -/- mice had significantly reduced ejection fraction (EF) compared to MasR +/+ mice at baseline (51.4 ± 2.5 vs 59.3 ± 2.1%; P<0.05) and after one month of HF-feeding (49.8 ± 2.4 vs 52.6 ± 1.9%; P<0.05). Further, CMR imaging demonstrated a thickening of the ventricle wall in MasR -/- mice with 1 month of HF-feeding. MasR +/+ , but not MasR -/- mice, exhibited diet-induced reductions in EF (by 16%; P<0.05) at 1 month of HF feeding, which were reversed by infusion of Ang-(1-7). These results demonstrate that MasR contributes to sexual dimorphism of obesity-hypertension. Ang-(1-7) protects females from obesity-hypertension through the MasR. In contrast, reductions in DBP in obese male mice with MasR deficiency may arise from deficits in cardiac function. These results suggest that MasR agonists may be effective therapies for obesity-associated cardiovascular conditions.

P–060 Dose- dependent mitigation of lead acetate toxicity in males on embryo development in female mice

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
P Dolati ◽  
M J Zamiri ◽  
A Akhlaghi ◽  
Z Jahromi
Keyword(s):  
Adverse Effects ◽  
Embryonic Development ◽  
Embryo Development ◽  
Lead Acetate ◽  
Endocrine System ◽  
Cell Number ◽  
The Other ◽  
Control Group ◽  
Male Mice ◽  
Female Mice

Abstract Study question Does quercetin (75 or 100 mg/kg BW/day) co-administration with lead acetate to male mice affects embryonic development in female mice? Summary answer The low-dose quercetin (75 mg/kg BW/day) ameliorated the adverse effects of lead acetate on mouse embryogenesis. What is known already Lead causes male infertility by impacting on endocrine system and spermatogenesis, and may exert undesirable effects on the offspring. The currently approved treatment for lead poisoning is the use of chelating agents, which form an insoluble complex with lead and shield it from biological targets; thus, reducing its toxicity. One of the main mechanisms of lead-induced toxicity is oxidative stress, and it has been reported that natural antioxidants can reduce the heavy metals toxicity. The aim of the present study was to examine the protective effects of quercetin on the toxicity induced by lead acetate on the embryogenesis in mice. Study design, size, duration Sexually mature (eight-week-old) NMRI male mice (n = 24) were randomly divided into four groups (n = 6 per group) receiving (i) distilled water (control group); (ii) lead acetate (150 mg/kg BW/day) dissolved in deionized water (LA); (iii) lead acetate (150 mg/kg BW/day) + quercetin (75 mg/kg BW/day) (LQ75); (IV) lead acetate (150 mg/kg BW/day) + quercetin (100 mg/kg BW/day) (LQ100). Treatments were applied daily as oral gavages for one cycle of the seminiferous epithelium (35 days). Participants/materials, setting, methods At the end of treatment administration, the males were joined with super-ovulated females, and the retrieved zygotes were cultured for evaluation of the embryo development (at 2-cell, 4-cell, 8-cell, and blastocyst stages), and blastocyst cell number using differential staining (propidium iodide and bisbenzimide). After incubation of capacitated sperm with oocytes, an ultraviolet light microscope was used following 3 min incubation with 25 µg⁄mL bisbenzamide solution for fertilization assessment. Main results and the role of chance Lead acetate (LA) treatment of male mice decreased the 2-cell stage compared with the control group (P &gt; 0.05). There was no difference between control and LQ75, and between LA and LQ100. The other stages of embryonic development were not significantly affected by the treatment. Overall, early embryonic development in the control and LQ75 mice were better than LQ100 and LA mice. The number of cells in the trophectoderm and inner-cell mass were not affected by treatments. However, the total blastocyst cell number in the control was higher than in the other groups; there was no significant difference between LQ100, LQ75 and LA groups. Fertilization rate was not affected by the treatments (P &lt; 0.05). Quercetin acts as a potent antioxidant at low doses, but at high doses exerts a pro-oxidant action. According to previous reports, higher concentrations of quercetin increased apoptosis and necrosis while decreasing the activities of the antioxidant enzymes. Also, it has been suggested that quercetin might disrupt the endocrine system and interfere with Sertoli cell function and sperm motility. Limitations, reasons for caution A limitation of this study is narrow dose selection; more studies are needed to determine the effective dose of quercetin in ameliorating the lead toxicity. There are also side effects of lead-quercetin chelates such as metal redistribution, essential metal loss, accumulation and persistency in intracellular sites, and peroxidation. Wider implications of the findings: Lead administration adversely impacted on the embryogenesis; on the other hand, paternal quercetin co-administration somewhat ameliorated the adverse effects of lead on mice embryogenesis. Trial registration number Not applicable

scholarly journals NPY Deficiency Prevents Postmenopausal Adiposity by Augmenting Estradiol-Mediated Browning

2018 ◽  
Vol 75 (6) ◽  
pp. 1042-1049
Author(s):  
Seongjoon Park ◽  
Erkhembayar Nayantai ◽  
Toshimitsu Komatsu ◽  
Hiroko Hayashi ◽  
Ryoichi Mori ◽  
...  
Keyword(s):  
Body Weight ◽  
Adipose Tissue ◽  
Fat Metabolism ◽  
Male Mice ◽  
Wild Type ◽  
Male And Female ◽  
Female Mice ◽  
Age Related ◽  
Promising Target ◽  
Intracellular Mechanism

Abstract The orexigenic hormone neuropeptide Y (NPY) plays a pivotal role in the peripheral regulation of fat metabolism. However, the mechanisms underlying the effects of sex on NPY function have not been extensively analyzed. In this study, we examined the effects of NPY deficiency on fat metabolism in male and female mice. Body weight was slightly decreased, whereas white adipose tissue (WAT) mass was significantly decreased as the thermogenic program was upregulated in NPY-/- female mice compared with that in wild-type mice; these factors were not altered in response to NPY deficiency in male mice. Moreover, lack of NPY resulted in an increase in luteinizing hormone (LH) expression in the pituitary gland, with concomitant activation of the estradiol-mediated thermogenic program in inguinal WAT, and alleviated age-related modification of adiposity in female mice. Taken together, these data revealed a novel intracellular mechanism of NPY in the regulation of fat metabolism and highlighted the sexual dimorphism of NPY as a promising target for drug development to reduce postmenopausal adiposity.

scholarly journals Gender differences in the response of CD-1 mouse bone to parathyroid hormone: potential role of IGF-I

2006 ◽  
Vol 189 (2) ◽  
pp. 279-287 ◽  
Author(s):  
Yongmei Wang ◽  
Takeshi Sakata ◽  
Hashem Z Elalieh ◽  
Scott J Munson ◽  
Andrew Burghardt ◽  
...  
Keyword(s):  
Gender Differences ◽  
Parathyroid Hormone ◽  
Cortical Bone ◽  
Mineral Apposition Rate ◽  
Mrna Levels ◽  
Male Mice ◽  
Bone Formation Rate ◽  
Male And Female ◽  
Female Mice ◽  
Igf I

Parathyroid hormone (PTH) exerts both catabolic and anabolic actions on bone. Studies on the skeletal effects of PTH have seldom considered the effects of gender. Our study was designed to determine whether the response of mouse bone to PTH differed according to sex. As a first step, we analyzed gender differences with respect to bone mass and structural properties of 4 month old PTH treated (80 μg/kg per day for 2 weeks) male and female CD-1 mice. PTH significantly increased fat free weight/body weight, periosteal bone formation rate, mineral apposition rate, and endosteal single labeling surface, while significantly decreasing medullary area in male mice compared with vehicle treated controls, but induced no significant changes in female mice. We then analyzed the gender differences in bone marrow stromal cells (BMSC) isolated from 4 month old male and female CD-1 mice following treatment with PTH (80 μg/kg per day for 2 weeks). PTH significantly increased the osteogenic colony number and the alkaline phosphatase (ALP) activity (ALP/cell) by day 14 in cultures of BMSCs from male and female mice. PTH also increased the mRNA level of receptor activator of nuclear factor κB ligand in the bone tissue (marrow removed) of both females and males. However, PTH increased the mRNA levels of IGF-I and IGF-IR only in the bones of male mice. Our results indicate that on balance a 2-weeks course of PTH is anabolic on cortical bone in this mouse strain. These effects are more evident in the male mouse. These differences between male and female mice may reflect the greater response to PTH of IGF-I and IGF-IR gene expression in males enhancing the anabolic effect on cortical bone.

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