Effect of Nitrogen Deficiency on Cell Growth and Fatty Acids Production of Nannochloropsis oculata K-1281

An oil from micro-algae rich in EPA with no DHA and consisting of 15% polar lipids (phospholipids and glycolipids) showed equivalent uptake of EPA into rat plasma and organs as omega-3 krill oil consisting of EPA and DHA and 40% phospholipids.

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Dietary Fatty Acids and Human Breast Cancer Cell Growth, Invasion, and Metastasis

Advances in Experimental Medicine and Biology - Diet and Breast Cancer ◽

10.1007/978-1-4615-2510-3_8 ◽

1994 ◽

pp. 83-91 ◽

Cited By ~ 28

Author(s):

David P. Rose ◽

Jeanne M. Connolly ◽

Xin-Hua Liu

Keyword(s):

Breast Cancer ◽

Fatty Acids ◽

Cell Growth ◽

Cancer Cell ◽

Breast Cancer Cell ◽

Human Breast Cancer ◽

Human Breast Cancer Cell ◽

Dietary Fatty Acids ◽

Cancer Cell Growth ◽

Breast Cancer Cell Growth

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Docosahexaenoic Acid has stem cell-specific effects in the SVZ and restores olfactory neurogenesis and function in the aging brain

10.1101/2020.02.10.942870 ◽

2020 ◽

Author(s):

JE Le Belle ◽

J Sperry ◽

K Ludwig ◽

NG Harris ◽

MA Caldwell ◽

...

Keyword(s):

Fatty Acids ◽

Stem Cells ◽

Stem Cell ◽

Cell Growth ◽

Olfactory Bulb ◽

Neural Stem Cells ◽

Egf Receptor ◽

Brain Repair ◽

Multipotent Stem Cells ◽

Growth And Survival

AbstractFatty acids are well known as important constituents for the synthesis of membrane lipids and as sources of cellular energy in the CNS. However, fatty acids can also act as vital second messenger molecules in the nervous system and regulate the activity of many proteins affecting cell growth and survival. Here, we show that an essential dietary fatty acid, Decosahexaenoic acid, (DHA), can enhance stem cell function in vitro and in vivo. We found that this effect is not due to an increase in the overall proliferation rate of all neural progenitors, but is due to an increase in the number of multipotent stem cells that leads to greater levels of subventricular zone (SVZ) neurogenesis with restoration of olfactory function in aged mice. These effects were likely mediated through increased EGF-receptor sensitivity, a conversion of EGRFR+ progenitors back into an EGRFR+/GFAP+ stem cell state, and the activation of the PI3K/AKT signaling pathway, which is a critical pathway in many NSC cell functions including cell growth and survival. Together these data demonstrate that neural stem cells in the aged and quiescent neurogenic niche of the mouse SVZ retain their ability to self-renew and contribute to neurogenesis when apparently rejuvenated by DHA and PI3K/AKT pathway activation. DHA stimulation of this signaling enhances the number of multipotent stem cells and neurogenesis in young and aged rodent and human stem cells and hence may have implications for the manipulation of neural stem cells for brain repair.Significance StatementWe have identified potentially important effects of DHA on the stem cell population which may be unique to the SVZ stem cell niche. Our studies demonstrate that DHA can promote the production of neural stem cells, possibly via a non-proliferative mechanism stimulated by EGF receptor activation, and prolongs their viability. Aging animals undergo an apparent loss in SVZ stem cells and an associated decline in olfactory bulb function. We find that dietary DHA supplementation at least partially restores stem cell numbers, olfactory bulb neurogenesis and olfactory discrimination and memory in aged mice, demonstrating a capacity for rejuvenation is retained despite age-related changes to the niche, which has significant implications for ameliorating cognitive decline in aging and for endogenous brain repair.

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DGAT1 is a lipid metabolism oncoprotein that enables cancer cells to accumulate fatty acid while avoiding lipotoxicity

10.1101/2020.06.23.166603 ◽

2020 ◽

Cited By ~ 1

Author(s):

Daniel J. Wilcock ◽

Andrew P. Badrock ◽

Rhys Owen ◽

Melissa Guerin ◽

Andrew D. Southam ◽

...

Keyword(s):

Fatty Acids ◽

Fatty Acid ◽

Cell Growth ◽

Cancer Cells ◽

Melanoma Cell ◽

Drug Targets ◽

Lipid Peroxides ◽

Acid Oxidation ◽

Growth Factor Signaling ◽

Bona Fide

ABSTRACTDysregulated cellular metabolism is a hallmark of cancer. As yet, few druggable oncoproteins directly responsible for this hallmark have been identified. Increased fatty acid acquisition allows cancer cells to meet their membrane biogenesis, ATP, and signaling needs. Excess fatty acids suppress growth factor signaling and cause oxidative stress in non-transformed cells, but surprisingly not in cancer cells. Molecules underlying this cancer adaptation may provide new drug targets. Here, we identify Diacylglycerol O-acyltransferase 1 (DGAT1), an enzyme integral to triacylglyceride synthesis and lipid droplet formation, as a frequently up-regulated oncoprotein allowing cancer cells to tolerate excess fatty acids. DGAT1 over-expression alone induced melanoma in zebrafish melanocytes, and co-operated with oncogenic BRAF or NRAS for more rapid melanoma formation. Mechanistically, DGAT1 stimulated melanoma cell growth through sustaining mTOR kinase–S6 kinase signaling and suppressed cell death by tempering fatty acid oxidation, thereby preventing accumulation of reactive oxygen species including lipid peroxides.SIGNIFICANCEWe show that DGAT1 is a bona fide oncoprotein capable of inducing melanoma formation and co-operating with other known drivers of melanoma. DGAT1 facilitates enhanced fatty acid acquisition by melanoma cells through suppressing lipototoxicity. DGAT1 is also critical for maintaining S6K activity required for melanoma cell growth.

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Epstein–Barr virus-encoded latent membrane protein 1 and B-cell growth transformation induces lipogenesis through fatty acid synthase.

Journal of Virology ◽

10.1128/jvi.01857-20 ◽

2020 ◽

Author(s):

Michael Hulse ◽

Sarah M Johnson ◽

Sarah Boyle ◽

Lisa Beatrice Caruso ◽

Italo Tempera

Keyword(s):

Fatty Acids ◽

Fatty Acid ◽

B Cells ◽

Cell Growth ◽

B Cell ◽

Fatty Acid Synthase ◽

De Novo ◽

Ectopic Expression ◽

Barr Virus ◽

Growth Transformation

Latent membrane protein 1 (LMP1) is the major transforming protein of Epstein-Barr virus (EBV) and is critical for EBV-induced B-cell transformation in vitro. Several B-cell malignancies are associated with latent LMP1-positive EBV infection, including Hodgkin’s and diffuse large B-cell lymphomas. We have previously reported that promotion of B cell proliferation by LMP1 coincided with an induction of aerobic glycolysis. To further examine LMP1-induced metabolic reprogramming in B cells, we ectopically expressed LMP1 in an EBV-negative Burkitt’s lymphoma (BL) cell line preceding a targeted metabolic analysis. This analysis revealed that the most significant LMP1-induced metabolic changes were to fatty acids. Significant changes to fatty acid levels were also found in primary B cells following EBV-mediated B-cell growth transformation. Ectopic expression of LMP1 and EBV-mediated B-cell growth transformation induced fatty acid synthase (FASN) and increased lipid droplet formation. FASN is a crucial lipogenic enzyme responsible for de novo biogenesis of fatty acids in transformed cells. Furthermore, inhibition of lipogenesis caused preferential killing of LMP1-expressing B cells and significantly hindered EBV immortalization of primary B-cells. Finally, our investigation also found that USP2a, a ubiquitin-specific protease, is significantly increased in LMP1-positive BL cells and mediates FASN stability. Our findings demonstrate that ectopic expression of LMP1 and EBV-mediated B-cell growth transformation leads to induction of FASN, fatty acids and lipid droplet formation, possibly pointing to a reliance on lipogenesis. Therefore, the use of lipogenesis inhibitors could potentially be used in the treatment of LMP1+ EBV associated malignancies by targeting a LMP1-specific dependency on lipogenesis. Importance Despite many attempts to develop novel therapies, EBV-specific therapies currently remain largely investigational and EBV-associated malignancies are often associated with a worse prognosis. Therefore, there is a clear demand for EBV-specific therapies for both prevention and treatment of viral-associated malignancies. Non-cancerous cells preferentially obtain fatty acids from dietary sources whereas cancer cells will often produce fatty acids themselves by de novo lipogenesis, often becoming dependent on the pathway for cell survival and proliferation. LMP1 and EBV-mediated B-cell growth transformation leads to induction of FASN, a key enzyme responsible for the catalysis of endogenous fatty acids. Preferential killing of LMP1-expressing B cells following inhibition of FASN suggests that targeting LMP-induced lipogenesis could be an effective strategy in treating LMP1-positive EBV-associated malignancies. Importantly, targeting unique metabolic perturbations induced by EBV could be a way to explicitly target EBV-positive malignancies and distinguish their treatment from EBV-negative counterparts.

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