scholarly journals Cyclopamine and Rapamycin Synergistically Inhibit mTOR Signalling in Mouse Hepatocytes, Revealing an Interaction of Hedgehog and mTor Signalling in the Liver

Cells ◽  
2020 ◽  
Vol 9 (8) ◽  
pp. 1817
Author(s):  
Luise Spormann ◽  
Christiane Rennert ◽  
Erik Kolbe ◽  
Fritzi Ott ◽  
Carolin Lossius ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Energy Homeostasis ◽  
In Vitro Studies ◽  
Primary Hepatocytes ◽  
Male And Female ◽  
Atp Production ◽  
Female Mice ◽  
Oxidative Respiration ◽  
Mtor Signalling

In the liver, energy homeostasis is mainly regulated by mechanistic target of rapamycin (mTOR) signalling, which influences relevant metabolic pathways, including lipid metabolism. However, the Hedgehog (Hh) pathway is one of the newly identified drivers of hepatic lipid metabolism. Although the link between mTOR and Hh signalling was previously demonstrated in cancer development and progression, knowledge of their molecular crosstalk in healthy liver is lacking. To close this information gap, we used a transgenic mouse model, which allows hepatocyte-specific deletion of the Hh pathway, and in vitro studies to reveal interactions between Hh and mTOR signalling. The study was conducted in male and female mice to investigate sexual differences in the crosstalk of these signalling pathways. Our results reveal that the conditional Hh knockout reduces mitochondrial adenosine triphosphate (ATP) production in primary hepatocytes from female mice and inhibits autophagy in hepatocytes from both sexes. Furthermore, in vitro studies show a synergistic effect of cyclopamine and rapamycin on the inhibition of mTor signalling and oxidative respiration in primary hepatocytes from male and female C57BL/6N mice. Overall, our results demonstrate that the impairment of Hh signalling influences mTOR signalling and therefore represses oxidative phosphorylation and autophagy.

In Vitro Studies of Oligodendroglial Lipid Metabolism

1984 ◽  
pp. 175-197 ◽  
Author(s):  
David Pleasure ◽  
Seung U. Kim ◽  
Donald H. Silberberg
Keyword(s):  
Lipid Metabolism ◽  
In Vitro Studies

THE ROLE OF TESTOSTERONE AND ANDROSTENEDIONE AS PRECURSORS OF EPITESTOSTERONE IN GUINEA PIGS (IN VIVO AND IN VITRO STUDIES)

1971 ◽  
Vol 67 (1) ◽  
pp. 187-196 ◽  
Author(s):  
Marian Szamatowicz ◽  
Michel Drosdowsky ◽  
Max F. Jayle
Keyword(s):  
Sex Differences ◽  
Guinea Pigs ◽  
In Vitro Studies ◽  
Male And Female ◽  
Testosterone Production ◽  
Liver Slices

ABSTRACT After injection of [7α-3H] androstenedione and [4-14C] testosterone into male and female guinea pigs, doubly labelled aetiocholanolone, 5α-androstanedione and epiandrosterone were identified in the urine. No epitestosterone was detected. Ovaries, testes, adrenals and liver slices were incubated with the same precursors. Epitestosterone production was observed in all organs except in the adrenals. According to the epitestosterone 3H/14C ratio, it can be concluded that in guinea pigs an interconversion of testosterone, androstenedione and epitestosterone takes place. In liver, androstenedione is preferentially converted to epitestosterone without sex differences, whereas in ovary and testis epitestosterone derives preferentially from testosterone.

scholarly journals Creatine Metabolism in Female Reproduction, Pregnancy and Newborn Health

Nutrients ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 490 ◽  
Author(s):  
Anna Maria Muccini ◽  
Nhi T. Tran ◽  
Deborah L. de Guingand ◽  
Mamatha Philip ◽  
Paul A. Della Gatta ◽  
...  
Keyword(s):  
Energy Homeostasis ◽  
De Novo ◽  
Creatine Supplementation ◽  
Perinatal Outcomes ◽  
Small Animal ◽  
Newborn Health ◽  
Female Reproduction ◽  
Atp Production ◽  
Creatine Metabolism

Creatine metabolism is an important component of cellular energy homeostasis. Via the creatine kinase circuit, creatine derived from our diet or synthesized endogenously provides spatial and temporal maintenance of intracellular adenosine triphosphate (ATP) production; this is particularly important for cells with high or fluctuating energy demands. The use of this circuit by tissues within the female reproductive system, as well as the placenta and the developing fetus during pregnancy is apparent throughout the literature, with some studies linking perturbations in creatine metabolism to reduced fertility and poor pregnancy outcomes. Maternal dietary creatine supplementation during pregnancy as a safeguard against hypoxia-induced perinatal injury, particularly that of the brain, has also been widely studied in pre-clinical in vitro and small animal models. However, there is still no consensus on whether creatine is essential for successful reproduction. This review consolidates the available literature on creatine metabolism in female reproduction, pregnancy and the early neonatal period. Creatine metabolism is discussed in relation to cellular bioenergetics and de novo synthesis, as well as the potential to use dietary creatine in a reproductive setting. We highlight the apparent knowledge gaps and the research “road forward” to understand, and then utilize, creatine to improve reproductive health and perinatal outcomes.

In vitro studies of lipid metabolism in human liver

1987 ◽  
Vol 113 (2) ◽  
pp. 482-487 ◽  
Author(s):  
Bo Angelin ◽  
Eva Reihnér ◽  
Mats Rudling ◽  
Staffan Ewerth ◽  
Ingemar Björkhem ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Human Liver ◽  
In Vitro Studies

Abstract 153: Inhibition of the 5-a-reductase Reduces Cardiac Hypertrophy and Improves Cardiac Function

2013 ◽  
Vol 113 (suppl_1) ◽  
Author(s):  
Carolin Zwadlo ◽  
Natali Froese ◽  
Johann Bauersachs ◽  
Joerg Heineke
Keyword(s):  
Cardiac Hypertrophy ◽  
Weight Ratio ◽  
Capillary Density ◽  
Left Ventricular ◽  
Heart Weight ◽  
Rat Cardiomyocytes ◽  
Male And Female ◽  
Female Mice

Objectives: Left ventricular hypertrophy (LVH) is an independent risk factor for increased cardiovascular mortality and a precursor of heart failure. Gender-specific differences point to a pivotal role of androgens in the development of pathological LVH. Dihydrotestosterone (DHT) is metabolized from testosterone via the enzyme 5-α-reductase. The 5-α-reductase is upregulated in the hypertrophied myocardium, leading to our assumption that DHT rather than testosterone is the crucial component in the development of LVH and might therefore constitute a potential therapeutic target. Methods: One week after transverse aortic constriction (TAC) or sham surgery male wild-type mice were treated for 2 weeks via an oralgastric tube with the 5-α-reductase inhibitor finasteride (daily dose 25mg/kg BW) or were left untreated (controls). Male and female transgenic Gαq (TG, a model of dilative cardiomyopathy) or non-transgenic mice were treated with finasteride for 6 weeks. Results: Cardiac hypertrophy after TAC was dramatically reduced by finasteride in male mice (heart weight/ body weight ratio, HW/BW in mg/g: control 6.65±0.35 versus finasteride treated 5.23±0.3; p<0.01). The reduced hypertrophy in these mice was accompanied by a reduction in cardiomyocyte diameter, ANP expression and fibrosis, but increased capillary density and Serca2a expression. Accordingly, finasteride also markedly reduced hypertrophy in isolated primary rat cardiomyocytes in vitro . Amelioration of hypertrophy by finasteride was associated with blunted activation of the prohypertrophic kinase mTOR in vitro and in vivo . Left ventricular dilation in male Gαq TG mice was markedly reduced by treatment with finasteride, which also led to an improvement in left ventricular function (determined as fractional area change in % by echocardiography: finasteride 44.72±1.71 vs. control 32.8±3.84, p<0.05) and a similar trend was observed in female mice. Interestingly, finasteride reduced pulmonary congestion in male and female mice alike. Conclusion: Finasteride treatment reduces hypertrophy and eccentric cardiac remodelling in mice, indicating a possible involvement of DHT in these processes as well as a potential benefit of 5-α-reductase inhibition in cardiac disease.

In vitro studies on oxidative and lipid metabolism in the immature macaque monkey

1962 ◽  
Vol 2 (5) ◽  
pp. 388-399 ◽  
Author(s):  
J.T. Van Bruggen ◽  
J.C. Elwood ◽  
Alicia Marcó ◽  
W.C. Bernards
Keyword(s):  
Lipid Metabolism ◽  
Macaque Monkey ◽  
In Vitro Studies

scholarly journals Estrogen responsiveness of bone formation in vitro and altered bone phenotype in aged estrogen receptor-α-deficient male and female mice

2005 ◽  
Vol 152 (2) ◽  
pp. 301-314 ◽  
Author(s):  
Vilhelmiina Parikka ◽  
ZhiQi Peng ◽  
Teuvo Hentunen ◽  
Juha Risteli ◽  
Teresa Elo ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Formation ◽  
Bone Marrow Cells ◽  
Type I ◽  
Wild Type ◽  
Male And Female ◽  
Female Mice ◽  
Bone Phenotype ◽  
Marrow Cells

Objective: Although the beneficial effects of estrogen on bone are well known, the roles of estrogen receptors (ERs) in mediating these effects are not fully understood. Methods: To study the effects of long-term ERα deficiency, bone phenotype was studied in aged ERα knockout (ERKO) mice. In addition, ERKO osteoclasts and osteoblasts were cultured in vitro. Design and results: Histomorphometric analysis showed that the trabecular bone volume and thickness were significantly increased and the rate of bone formation enhanced in both male and female ERKO mice in comparison to the wild-type animals. In ERKO males, however, the bones were thinner and their maximal bending strengths decreased. Consistent with previous reports, the bones of knockout mice, especially of female mice, were shorter than those of wild-type mice. In addition, the growth plates were totally absent in the tibiae of aged ERKO females, whereas the growth plate cartilages were detectable in wild-type females as well as in all the males. Analysis of cultured bone marrow cells from 10- to 12-week-old mice demonstrated that 17β-estradiol could stimulate osteoblastic differentiation of bone marrow cells derived from ERKO mice relatively to the same extent as those derived from wild-type mice. This was demonstrated by increases in synthesis of type I collagen, activity of alkaline phosphatase and accumulation of calcium in cultures. Total protein content was, however, reduced in ERKO osteoblast cultures. Conclusions: These results show altered bone phenotype in ERKO mice and demonstrate the stimulatory effect of estrogen on osteoblasts even in the absence of full-length ERα.

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