PTEN: A Thrifty Gene That Causes Disease in Times of Plenty?

Venniyoor, Ajit

doi:10.3389/fnut.2020.00081

Cited by 17 publications

(15 citation statements)

References 159 publications

(129 reference statements)

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“…PCa is characterized by an activation of the PI3K-AKT-mTOR (phosphatidylinositol-3-kinase [PI3K], protein kinase B [PKB/AKT], and mTOR) pathway [ 131 ] and deficiency of PTEN (phosphatase and tensin homolog deleted on chromosome 10), a tumor suppressor gene that inhibits the PI3K-AKT-mTOR pathway, is associated with PCa [ 132 ]. Metformin is an AMPK activator and induces PTEN [ 133 ]. Therefore, metformin is potentially effective in the inhibition of PCa.…”

Section: Prostate-related Healthmentioning

confidence: 99%

The Effect of Metformin on Male Reproductive Function and Prostate: An Updated Review

Tseng

2022

World J Mens Health

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Metformin is the first-line oral antidiabetic drug that shows multiple pleiotropic effects of anti-inflamation, anti-cancer, anti-aging, anti-microbia, anti-atherosclerosis, and immune modulation. Metformin's effects on men's related health are reviewed here, focusing on reproductive health under subtitles of erectile dysfunction (ED), steroidogenesis and spermatogenesis; and on prostate-related health under subtitles of prostate specific antigen (PSA), prostatitis, benign prostate hyperplasia (BPH), and prostate cancer (PCa). Updated literature suggests a potential role of metformin on arteriogenic ED but controversial and contradictory effects (either protective or harmful) on testicular functions of testosterone synthesis and spermatogenesis. With regards to prostate-related health, metformin use may be associated with lower levels of PSA in humans, but its clinical implications require more research. Although there is a lack of research on metform's effect on prostatitis, it may have potential benefits through its anti-microbial and anti-inflammatory properties. Metformin may reduce the risk of BPH by inhibiting the insulin-like growth factor 1 pathway and some but not all studies suggest a protective role of metformin on the risk of PCa. Many clinical trials are being conducted to investigate the use of metformin as an adjuvant therapy for PCa but results currently available are not conclusive. While some trials suggest a benefit in reducing the metastasis and recurrence of PCa, others do not show any benefit. More research works are warranted to illuminate the potential usefulness of metformin in the promotion of men's health.

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Section: Prostate-related Healthmentioning

confidence: 99%

The Effect of Metformin on Male Reproductive Function and Prostate: An Updated Review

Tseng

2022

World J Mens Health

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“…RRN3 expression is regulated by environmental factors, reduced by caloric and other nutrient restriction and sensitive to AA availability and mTORC1 signalling [91,92,102]. Indeed, PTEN, the negative regulator of mTORC1, has been proposed as a thrifty gene to drive metabolic storage when nutrients are plentiful [103]. We can, therefore, postulate a stepwise progression in the timeline of Emb-LPD/LPD programming from its induction in the embryo through mTORC1, discussed below.…”

Section: Blastocyst Nutrient Sensing Coordinates the Foetal Growth Trajectorymentioning

confidence: 99%

Environmental Exposures around Conception: Developmental Pathways Leading to Lifetime Disease Risk

Fleming

Sun

Denisenko

et al. 2021

IJERPH

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Environment around conception can influence the developmental programme with lasting effects on gestational and postnatal phenotype and with consequences for adult health and disease risk. Peri-conception exposure comprises a crucial part of the ‘Developmental Origins of Health and Disease’ (DOHaD) concept. In this review, we consider the effects of maternal undernutrition experienced during the peri-conception period in select human models and in a mouse experimental model of protein restriction. Human datasets indicate that macronutrient deprivation around conception affect the epigenome, with enduring effects on cardiometabolic and neurological health. The mouse model, comprising maternal low protein diet exclusively during the peri-conception period, has revealed a stepwise progression in altered developmental programming following induction through maternal metabolite deficiency. This progression includes differential effects in extra-embryonic and embryonic cell lineages and tissues, leading to maladaptation in the growth trajectory and increased chronic disease comorbidities. The timeline embraces an array of mechanisms across nutrient sensing and signalling, cellular, metabolic, epigenetic and physiological processes with a coordinating role for mTORC1 signalling proposed. Early embryos appear active participants in environmental sensing to optimise the developmental programme for survival but with the trade-off of later disease. Similar adverse health outcomes may derive from other peri-conception environmental experiences, including maternal overnutrition, micronutrient availability, pollutant exposure and assisted reproductive treatments (ART) and support the need for preconception health before pregnancy.

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“…Pten dosage is closely related to the severity of various diseases [ 23 , 24 , 31 ], and Pten conditional loss in HSPCs leads to leukemia [ 19 – 21 ]. However, mice with Pten-specific half-deficient HSPCs were phenotypically normal and used as a control to study the role of Pten in hematopoiesis [ 19 , 20 ].…”

Section: Discussionmentioning

confidence: 99%

Disruption of hematopoiesis attenuates the osteogenic differentiation capacity of bone marrow stromal cells

et al. 2022

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Background The homeostasis of mesenchymal stem cells (MSCs) is modulated by both their own intracellular molecules and extracellular milieu signals. Hematopoiesis in the bone marrow is maintained by niche cells, including MSCs, and it is indispensable for life. The role of MSCs in maintaining hematopoietic homeostasis has been fully elucidated. However, little is known about the mechanism by which hematopoietic cells reciprocally regulate niche cells. The present study aimed to explore the close relationship between MSCs and hematopoietic cells, which may be exploited for the development of new therapeutic strategies for related diseases. Methods In this study, we isolated cells from the offspring of Tie2Cre + and Ptenflox/flox mice. After cell isolation and culture, we investigated the effect of hematopoietic cells on MSCs using various methods, including flow cytometry, adipogenic and osteogenic differentiation analyses, quantitative PCR, western bloting, and microCT analysis. Results Our results showed that when the phosphatase and tensin homolog deleted on chromosome 10 (Pten) gene was half-deleted in hematopoietic cells, hematopoiesis and osteogenesis were normal in young mice; the frequency of erythroid progenitor cells in the bone marrow gradually decreased and osteogenesis in the femoral epiphysis weakened as the mice grew. The heterozygous loss of Pten in hematopoietic cells leads to the attenuation of osteogenic differentiation and enhanced adipogenic differentiation of MSCs in vitro. Co-culture with normal hematopoietic cells rescued the abnormal differentiation of MSCs, and in contrast, MSCs co-cultured with heterozygous null Pten hematopoietic cells showed abnormal differentiation activity. Co-culture with erythroid progenitor cells also revealed them to play an important role in MSC differentiation. Conclusion Our data suggest that hematopoietic cells function as niche cells of MSCs to balance the differentiation activity of MSCs and may ultimately affect bone development.

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PTEN: A Thrifty Gene That Causes Disease in Times of Plenty?

Cited by 17 publications

References 159 publications

The Effect of Metformin on Male Reproductive Function and Prostate: An Updated Review

The Effect of Metformin on Male Reproductive Function and Prostate: An Updated Review

Environmental Exposures around Conception: Developmental Pathways Leading to Lifetime Disease Risk

Disruption of hematopoiesis attenuates the osteogenic differentiation capacity of bone marrow stromal cells

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