Cholesterol: Biosynthesis, Functional Diversity, Homeostasis and Regulation by Natural Products

Thomas, J. P.; Shentu, Tzu‐Pin; Singh, Devinder

doi:10.5772/32538

Cited by 12 publications

(12 citation statements)

References 86 publications

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“…Replacing FM with SBM decreases the blood cholesterol level of fish, and the cholesterol-lowering effect of SBM is positively associated with its growth-depressing action ( 2 , 8 , 9 ) . Cholesterol, a vital component of cell membranes and the precursor of bile acids, steroid and hormones, is essential for diverse cellular functions ( 32 ) . Thus, cholesterol supplementation may be required as plant-derived protein sources (such as SBM, cottonseed meal and rapeseed meal) become the main protein source in fish feeds ( 4 , 5 , 19 ) .…”

Section: Discussionmentioning

confidence: 99%

Improving the growth performance and cholesterol metabolism of rainbow trout (Oncorhynchus mykiss) fed soyabean meal-based diets using dietary cholesterol supplementation

Deng

Kang

et al. 2012

Br J Nutr

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A 9-week feeding trial was conducted to evaluate the effects of dietary cholesterol supplementation at different levels (0, 0·3, 0·6, 0·9, 1·2 and 1·5 %) on growth and cholesterol metabolism of rainbow trout (Oncorhynchus mykiss) fed soyabean meal (SBM)-based diets. Daily growth coefficient (DGC) steadily increased when the supplemental cholesterol was increased by up to 1·2 %, but declined upon further addition. The total cholesterol (TC), HDL-cholesterol (HDL-C) and LDL-cholesterol (LDL-C) levels in plasma generally increased when the supplemental cholesterol was increased by up to 1·2 %. Thereafter, the TC level reached a plateau, the LDL-C level showed a marked decline, whereas the HDL-C level continued to increase. Dietary cholesterol supplementation generally increased the total lipid and cholesterol levels in liver; the total lipid and TAG levels in muscle; the TC, free cholesterol, cholesteryl ester and total bile acid levels in intestinal contents; and the triiodothyronine and Ca levels in plasma. However, significant differences were mainly observed with high levels of supplemental cholesterol (0·9-1·5 %). Low levels of supplemental cholesterol (0·3-0·9 %) decreased hepatic 3-hydroxy-3-methyl-glutaryl-CoA reductase and cholesterol 7a-hydroxylase activities, but high levels of supplemental cholesterol (1·5 %) increased hepatic acyl-CoA:cholesterol acyl transferase and cholesterol 7a-hydroxylase activities. These results suggest that rainbow trout fed SBM-based diets have a certain 'cholesterol-buffering capacity', which in turn suggests the possibility of the inhibition of exogenous cholesterol absorption and/or inadequate endogenous production of cholesterol in trout fed SBM-based diets. DGC increased steadily with increasing supplemental cholesterol level up to 1·2 %, and the growth-promoting effects might be related to the alleviation of the negative effects caused by a soyabean diet and/or make up for the deficiency of endogenous cholesterol in rainbow trout.

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Section: Discussionmentioning

confidence: 99%

Improving the growth performance and cholesterol metabolism of rainbow trout (Oncorhynchus mykiss) fed soyabean meal-based diets using dietary cholesterol supplementation

Deng

Kang

et al. 2012

Br J Nutr

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“…cholesterol metabolism target (Shobab et al, 2005). We (Thomas et al, 2012). Thus, abnormal concentrations of 508 27-OHC induced cholesterol-loaded and increased FC 509 levels in the brain (Fig.…”

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confidence: 90%

27-Hydroxycholesterol contributes to disruptive effects on learning and memory by modulating cholesterol metabolism in the rat brain

Zhang

et al. 2015

Neuroscience

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“…RNA sequencing indicates that SMAD7 functions by regulating multiple genes in the cholesterol biosynthesis pathway in TEL-AML1 + cells. Thomas, 2012). In addition to cholesterol being obtained from the diet, almost 50% of cholesterol in the body is derived from de novo synthesis (Berg JM, 2002).…”

Section: Discussionmentioning

confidence: 99%

“…The majority of body cholesterol is synthesised by the liver and secreted as circulating lipoproteins. The process of cholesterol synthesis involves multiple enzymes and stages, but it can be broken down into five major steps (Berg JM, 2002;J. Thomas, 2012):…”

Section: Discussionmentioning

confidence: 99%

Aberrant transcriptional pathways in t(12;21) Acute Lymphoblastic Leukemia

et al. 2016

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The single most frequent chromosomal translocation associated with childhood Acute Lymphoblastic Leukaemia is the t(12;21) rearrangement, that creates a fusion gene between TEL (ETV6) and AML1 (RUNX1). Although TEL-AML1 + patients have a very good prognosis, relapses occur in up to 20% of cases and many patients face long-term side effects of chemotherapy. Our laboratory has previously shown that TEL-AML1 regulates Signal Transducer and Activator of Transcription 3 (STAT3) activation, which is critical for survival of the leukaemic cells. In this study, inhibition of STAT3 in TEL-AML1 + cells results in decreased SMAD7 gene expression. SMAD7 is an antagonist of TGF-β signalling, functioning through a negative feedback mechanism, but is also known to function in other biological pathways. In order to investigate the role of SMAD7 in TEL-AML1 + leukaemia, lentiviral mediated SMAD7 knockdown was performed in human TEL-AML1 + cell lines. SMAD7 silencing inhibited proliferation of TEL-AML1 + cell lines, eventually leading to growth arrest and apoptosis. Furthermore, our data showed that this effect is not mediated through TGF-β signalling, indicating that SMAD7 was functioning through an alternative pathway. We also observed growth arrest following SMAD7 knockdown in other ALL and AML subtypes. Furthermore, silencing of SMAD7 in TEL-AML1 + ALL cells transplanted into immunodeficient mice impaired disease progression in vivo, resulting in prolonged disease latency. To investigate the essential pathways regulated by SMAD7 in these leukaemic cells, we performed RNA-sequencing analysis on TEL-AML1 + cells following SMAD7 knockdown. Global gene expression analysis revealed SMAD7 to be a regulator of cholesterol biosynthesis, a pathway critical for leukaemia cell survival. Our

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Cholesterol: Biosynthesis, Functional Diversity, Homeostasis and Regulation by Natural Products

Cited by 12 publications

References 86 publications

Improving the growth performance and cholesterol metabolism of rainbow trout (Oncorhynchus mykiss) fed soyabean meal-based diets using dietary cholesterol supplementation

Improving the growth performance and cholesterol metabolism of rainbow trout (Oncorhynchus mykiss) fed soyabean meal-based diets using dietary cholesterol supplementation

27-Hydroxycholesterol contributes to disruptive effects on learning and memory by modulating cholesterol metabolism in the rat brain

Aberrant transcriptional pathways in t(12;21) Acute Lymphoblastic Leukemia

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