Abstract 628: Efficient Excretion of Xenosterols in the Absence of Abcg5/Abcg8

2016 ◽  
Vol 36 (suppl_1) ◽  
Author(s):  
Shailendra B Patel
Keyword(s):  
Body Weight ◽  
Plant Sterols ◽  
Whole Body ◽  
Pathological Changes ◽  
Rapid Loss ◽  
Male And Female ◽  
Female Mice ◽  
Kinetics Of ◽  
Sterol Trafficking

Hypothesis: Xenosterol excretion by the mammalian body is wholly dependent on Abcg5/Abcg8 function. Methods: To test our hypothesis, we loaded Abcg8-/- mice with dietary plant sterols until they manifested biochemical (elevated plant sterols) and pathological changes (poor body weight, macrothrombocytopenia). All dietary xenosterols were eliminated from the diet and kinetics of xenosterol loss monitored over the ensuing 16 days, monitoring plasma, bile, and stool losses, as well as whole body sterol determinations. Results: After loading Abcg8-/- mice with plant sterols, plasma sitosterol levels in both male and female mice averaged 80mg/dL. Surprisingly, there was rapid loss of xenosterols from blood as well as tissues (liver, whole body), with losses of xenosterols detected in bile and feces. By day 16, stool xenosterols were almost undetectable and reflected the dramatic loss of whole body xenosterols. Conclusions: Our data refute our hypothesis. Although loss of sterolin function leads to severe xenosterolemia in both humans and mice, at least in mice, there appears to be a pathway(s) for elimination via the biliary/intestinal route. Characterization of the transporters involved may shed further light on sterol trafficking.

Rate of loss of radioiron from mouse and man

1960 ◽  
Vol 198 (4) ◽  
pp. 784-786 ◽  
Author(s):  
John D. Bonnet ◽  
Alan L. Orvis ◽  
Albert B. Hagedorn ◽  
Charles A. Owen
Keyword(s):  
Life Span ◽  
Half Life ◽  
Whole Body ◽  
Entire Body ◽  
Rapid Loss ◽  
Male And Female ◽  
Female Mice ◽  
Steady Rate ◽  
Normal Man ◽  
The Difference

Forty-two male and female mice, 8 weeks old, were given radioiron (Fe59) in doses of 0.006–0.1 µc, containing 0.013–0.17 µg of iron, by intraperitoneal or intravenous routes. Assays of the radioactivity of the whole body revealed an initial rapid loss of Fe59 (15–20%) lasting about 6 days. Thereafter the Fe59 left the mice at a steady rate of 0.39%/day (half-life 180 days). One 34-year-old normal man was given 10.6 µc of Fe59, containing 8.2 µg of iron, intravenously. Based on counts from the entire body, the biologic rate of loss of the Fe59 was about 0.14%/day (half-life 500 days), and there was little or no initial loss such as occurred in the mouse. The Fe59 in the circulating erythrocytes was essentially unchanged for the first 3 months. It then fell to a new level of about 90% of the previous one; the mid-point of the fall was about 120 days after the administration of the radioiron. The difference in the rates of loss of radioiron from mice and man seems to be related primarily to the life span of the circulating red cells.

Toxicity of Astatine-211 in the Mouse

1988 ◽  
Vol 7 (6) ◽  
pp. 529-534 ◽  
Author(s):  
L.M. Cobb ◽  
A. Harrison ◽  
S.A. Butler
Keyword(s):  
Bone Marrow ◽  
Body Weight ◽  
Lymph Nodes ◽  
Salivary Glands ◽  
Single Injection ◽  
Pathological Changes ◽  
Male And Female ◽  
Female Mice

The toxicity of the α particle emitting halogen astatine-211 was examined in male and female mice. Pathological changes were seen in mice killed at 14 days and/or at 56 days following a single injection of 61 kBq211 At per g body weight. The tissues affected, in order of severity were: spleen, lymph nodes, bone marrow, gonads, thyroid, salivary glands and stomach.

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 Effects of Bisphenol-A (BPA) and black seed oil on body weight, lipid profile and serum glucose in male and female mice

2019 ◽  
Vol 17 (1) ◽  
Author(s):  
K. M. Sujan ◽  
E. Haque ◽  
M. S. Rakib ◽  
M. I. Haque ◽  
A. Mustari ◽  
...  
Keyword(s):  
Body Weight ◽  
Weight Gain ◽  
Bisphenol A ◽  
Lipid Profile ◽  
Seed Oil ◽  
Serum Glucose ◽  
Male And Female ◽  
Female Mice ◽  
Black Seed ◽  
Black Seed Oil

Background: Bisphenol-A [BPA, 2, 2-bis (hydroxyphenyl) propane] is widely used in the manufacture of polycarbonate plastic, water bottles, feeders , baby bottles, epoxy resins and inside coating in metallic food cans. Black seed oil (BSO) (Nigella sativa) commonly known as black cumin, reported to be beneficial in function of various systems in the body. The study was carried out to investigate the effect of BPA and BSO on body weight, lipid profile and serum glucose in male and female mice. Methods : A total of thirty (15 male and 15 female) Swiss Albino mice (Mus musculus), aged 25-28 days with an average body weight of 27.4±1g were randomly divided into 3 groups consisting 5 mice in each for each sex. Group A served as vehicle control. Group B was administered BPA @ 50 mg/kg bw daily, while group C received both BPA @ 50 mg/kg/day and BSO @ 1ml/kg/day respectively. Results: Data revealed that BPA treated mice showed slight increase in body weight gain while BSO controlled the weight gain in BPA treated mice. Cholesterol and LDL values were significantly (p<0.01) increased and Triglycerides value was significantly (p<0.01) decreased in BPA-treated mice without significant alterations in HDL value. BPA & BSO treated female mice showed significant (p<0.01) decreased in cholesterol, triglycerides and LDL values. BPA reduced the blood glucose level and addition of BSO had synergistic effects of glucose utilization. Conclusions: It can be concluded that BPA is one of the potential risk factors for hyperlipidemia and obesity. These harmful effects could be alleviated by the ingestion of black seed oil.

scholarly journals Tpcn2 knockout mice have improved insulin sensitivity and are protected against high-fat diet-induced weight gain

2018 ◽  
Vol 50 (8) ◽  
pp. 605-614
Author(s):  
Hong He ◽  
Katie Holl ◽  
Sarah DeBehnke ◽  
Chay Teng Yeo ◽  
Polly Hansen ◽  
...  
Keyword(s):  
Body Weight ◽  
Weight Gain ◽  
Insulin Sensitivity ◽  
Glucose Tolerance ◽  
Knockout Mice ◽  
High Fat Diet ◽  
Wild Type ◽  
High Fat ◽  
Male And Female ◽  
Female Mice

Type 2 diabetes is a complex disorder affected by multiple genes and the environment. Our laboratory has shown that in response to a glucose challenge, two-pore channel 2 ( Tpcn2) knockout mice exhibit a decreased insulin response but normal glucose clearance, suggesting they have improved insulin sensitivity compared with wild-type mice. We tested the hypothesis that improved insulin sensitivity in Tpcn2 knockout mice would protect against the negative effects of a high fat diet. Male and female Tpcn2 knockout (KO), heterozygous (Het), and wild-type (WT) mice were fed a low-fat (LF) or high-fat (HF) diet for 24 wk. HF diet significantly increases body weight in WT mice relative to those on the LF diet; this HF diet-induced increase in body weight is blunted in the Het and KO mice. Despite the protection against diet-induced weight gain, however, Tpcn2 KO mice are not protected against HF-diet-induced changes in glucose or insulin area under the curve during glucose tolerance tests in female mice, while HF diet has no significant effect on glucose tolerance in the male mice, regardless of genotype. Glucose disappearance during an insulin tolerance test is augmented in male KO mice, consistent with our previous findings suggesting enhanced insulin sensitivity in these mice. Male KO mice exhibit increased fasting plasma total cholesterol and triglyceride concentrations relative to WT mice on the LF diet, but this difference disappears in HF diet-fed mice where there is increased cholesterol and triglycerides across all genotypes. These data demonstrate that knockout of Tpcn2 may increase insulin action in male, but not female, mice. In addition, both male and female KO mice are protected against diet-induced weight gain, but this protection is likely independent from glucose tolerance, insulin sensitivity, and plasma lipid levels.

scholarly journals CTRP3 deficiency reduces liver size and alters IL-6 and TGFβ levels in obese mice

2016 ◽  
Vol 310 (5) ◽  
pp. E332-E345 ◽  
Author(s):  
Risa M. Wolf ◽  
Xia Lei ◽  
Zhi-Chun Yang ◽  
Maeva Nyandjo ◽  
Stefanie Y. Tan ◽  
...  
Keyword(s):  
Serum Levels ◽  
Whole Body ◽  
Activity Levels ◽  
Loss Of Function ◽  
Physiological Control ◽  
Liver Size ◽  
Male And Female ◽  
Female Mice ◽  
Obesity And Diabetes ◽  
Similar Weight

C1q/TNF-related protein 3 (CTRP3) is a secreted metabolic regulator whose circulating levels are reduced in human and rodent models of obesity and diabetes. Previously, we showed that CTRP3 infusion lowers blood glucose by suppressing gluconeogenesis and that transgenic overexpression of CTRP3 protects mice against diet-induced hepatic steatosis. Here, we used a genetic loss-of-function mouse model to further address whether CTRP3 is indeed required for metabolic homeostasis under normal and obese states. Both male and female mice lacking CTRP3 had similar weight gain when fed a control low-fat (LFD) or high-fat diet (HFD). Regardless of diet, no differences were observed in adiposity, food intake, metabolic rate, energy expenditure, or physical activity levels between wild-type (WT) and Ctrp3-knockout (KO) animals of either sex. Contrary to expectations, loss of CTRP3 in LFD- or HFD-fed male and female mice also had minimal or no impact on whole body glucose metabolism, insulin sensitivity, and fasting-induced hepatic gluconeogenesis. Unexpectedly, the liver sizes of HFD-fed Ctrp3-KO male mice were markedly reduced despite a modest increase in triglyceride content. Furthermore, liver expression of fat oxidation genes was upregulated in the Ctrp3-KO mice. Whereas the liver and adipose expression of profibrotic TGFβ1, as well as its serum levels, was suppressed in HFD-fed KO mice, circulating proinflammatory IL-6 levels were markedly increased; these changes, however, were insufficient to affect systemic metabolic outcome. We conclude that, although it is dispensable for physiological control of energy balance, CTRP3 plays a previously unsuspected role in modulating liver size and circulating cytokine levels in response to obesity.

scholarly journals Investigating the Role of Farnesoid X Receptor in Heme Biosynthesis and Ductular Reaction

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A810-A811
Author(s):  
Angela E Dean ◽  
Emilian Jungwirth ◽  
Katrin Panzitt ◽  
Martin Wagner ◽  
Sayeepriyadarshini Anakk
Keyword(s):  
Gene Expression ◽  
Body Weight ◽  
Weight Ratio ◽  
Heme Biosynthesis ◽  
Farnesoid X Receptor ◽  
Whole Body ◽  
Wild Type ◽  
Body Weight Ratio ◽  
Ductular Reaction ◽  
Male And Female

Abstract Bile acids (BAs) have gained traction not just as emulsifiers of fat, but also as hormones. Nuclear receptor Farnesoid X receptor (FXR) is the master regulator of BAs and can also control glucose and lipid metabolism. We examined if FXR contributed towards heme biosynthesis and induction of a ductular reaction. Male and female whole body Fxr knockout (FxrKO) mice, as well as liver- and intestine-specific knockouts (LFxrKO and IFxrKO, respectively) were treated with 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC, a ferrochelatase inhibitor) for two weeks. At the end of the two weeks, mice were fasted for four hours and euthanized. All groups of mice had lost a similar percentage of body weight when fed the DDC diet. However, female FxrKO mice had significantly increased liver to body weight ratio, while male FxrKO mice had significantly decreased liver to body weight ratio when fed the DDC diet compared with their wild type counterparts. Serum liver injury markers were analyzed and liver histology and changes in genes involved in the heme biosynthesis pathway were examined. Both male and female whole body FxrKO livers had decreased ductular reaction with minimal bile plugs (porphyrin accumulation) compared with their wild type counterparts. LFxrKO mice mimicked diminished ductular reaction, while IFxrKO mice exhibited severe ductular reaction similar to that of wild type mice, indicating that the ductular reaction is dependent on hepatic FXR. ChIP-Seq for FXR revealed binding peaks in the heme biosynthesis genes, Alas1, Alad, Uros, and Fech, suggesting that FXR may act as a transcription factor for these genes. Further investigation revealed that Pbgd gene expression was increased, while Fech gene expression was decreased in female FxrKO mice compared to wild type mice. In male mice, Pbgd, Uros, Urod, and Cpox gene expression was increased in the absence of Fxr. In conclusion, Fxr is necessary to mount a ductular reaction and plays a key role in heme biosynthesis in the liver.

scholarly journals Characterization of the immune response in male and female mice following lipopolysaccharide‐induced systemic inflammation (1096.10)

2014 ◽  
Vol 28 (S1) ◽  
Author(s):  
Nina Bubalo ◽  
Peter Nguyen ◽  
Tuan Nguyen ◽  
Tzvia Abramson ◽  
Katherine Wilkinson
Keyword(s):  
Immune Response ◽  
Systemic Inflammation ◽  
Male And Female ◽  
Female Mice
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