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Diagnosis and Pathobiology
Published in Franklyn De Silva, Jane Alcorn, The Elusive Road Towards Effective Cancer Prevention and Treatment, 2023
Franklyn De Silva, Jane Alcorn
The role of lipid metabolism in physiology is invaluable, especially its deregulation in human diseases such as metabolic diseases [427]. Lipids (e.g., fatty acids, isoprenoid, cholesterol) can modulate the localization and function of proteins by covalently modifying proteins, (typically involving fatty acyl or polyisoprenyl groups). These lipid modifications can be generally divided into two groups, namely lipidation that occurs in the lumen of the secretory pathway (e.g., glycosylphosphatidylinositol/GPI anchors), and lipidation that occur in the cytoplasm or on the cytoplasmic face of membranes (e.g., prenylation, N‐myristoylation, S‐palmitoylation/S-acylation) [396, 400, 428]. Among lipid modifications, acylation with myristic and palmitic acids are most common [401]. Hedgehog (Hh), Wnt, 5′ AMP-activated protein kinase/5′ adenosine monophosphate-activated protein kinase (AMPK), endothelial/epidermal growth factor receptor (EGFR), hippo yes-associated protein 1/transcriptional coactivator with PDZ-binding motif (YAP/TAZ), and rat sarcoma (Ras) pathway components and components of autophagy (e.g., autophagy-related protein 8/ATG8 lipidation, a hallmark of autophagy, and microtubule-associated protein light chain 3/LC3) are among the most frequent PTM lipids for cell signaling and intracellular trafficking [401, 429–432].
Free Radicals and Antioxidants
Published in Chuong Pham-Huy, Bruno Pham Huy, Food and Lifestyle in Health and Disease, 2022
Chuong Pham-Huy, Bruno Pham Huy
New biological functions of vitamin A such as lipid metabolism, insulin response, energy balance, and the nervous system, are continuously being discovered. Detailed roles, dosage, side effects, dietary sources of vitamin A and β-carotene are described in Chapter 2 of this book.
Fenugreek in Management of Primary Hyperlipidaemic Conditions
Published in Dilip Ghosh, Prasad Thakurdesai, Fenugreek, 2022
Subhash L. Bodhankar, Amit D. Kandhare, Amol P. Muthal
The accumulation of free fatty acids (FFAs) due to diet-induced obesity causes elevated TG levels in non-adipose tissues controlled by leptin has been well documented. However, alteration in leptin signalling results in lipotoxicity, increasing the risk of cardiovascular diseases (Poetsch, Strano, and Guan 2020). Elevated hepatic FFAs result in impaired glucose metabolism, contributing to non-alcoholic steatohepatitis (Ai et al. 2015). Additionally, in renal tissue, elevated levels of FFAs induce toxicity in proximal tubular epithelial cells, leading to renal damage (Liu et al. 2019). Thus, elevated levels of lipid can cause multiorgan failure. Lifestyle modification plays a vital role in the management of lipid metabolism disorders. Interestingly, intake of the Mediterranean diet and/or nuts can reduce LDL-C levels (Bao et al. 2013; Estruch et al. 2013). However, long-term diet compliance limits its clinical implication for the treatment of chronic hyperlipidaemia. Statins (including simvastatin, atorvastatin, and lovastatin) have a predominant effect lowering TC and LDL-C through down-regulation of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase enzymes (Parhofer 2016). Furthermore, some non-statin therapies such as ezetimibe, niacin, lomitapide, PCSK9 inhibitor (Alirocumab and Evolocumab) showed some positive benefits in halting the progression of atherosclerosis (Karr 2017). However, some patients produce adverse events or are intolerant or resistant to these therapies, or remain non-adherent, resulting in poor outcomes.
Targeting cellular energy metabolism- mediated ferroptosis by small molecule compounds for colorectal cancer therapy
Published in Journal of Drug Targeting, 2022
Gang Wang, Jun-Jie Wang, Xiao-Na Xu, Feng Shi, Xing-Li Fu
Activation of lipid metabolism is complicated, involving a large number of enzymes catalysing metabolic reactions with regulation at different levels, such as lipid uptake, fatty acid transport, fatty acid synthesis and oxidation [24]. Most important, the activation of monocytes by lipopolysaccharide (LPS) leads to cell enlargement and an increased demand for the biosynthesis of proteins, lipids, and DNA. To meet these requirements, stimulation of monocytes/macrophages by LPS is accompanied by a shift towards increased glycolytic flux in cancer cells [25,26]. In addition, due to the necessary synthesis of amino acids and lipids, upregulation of the pentose–phosphate pathway (PPP) occurs, secretion of lactate increases, and demand for intermediates in the TCA cycle increases [27] (Figure 1).
Vitamin D3 intake as modulator for the early biomarkers of myocardial tissue injury in diabetic hyperlipidaemic rats
Published in Archives of Physiology and Biochemistry, 2022
Mohamed M. Elseweidy, Sousou I. Ali, Noura I. Shershir, Abd Elmonem A. Ali, Sally K. Hammad
In our study, vitamin D significantly improved the lipid profile in diabetic rats. This is consistent with other studies, where vitamin D improved the lipid profile not only in experimental animals, but also in patients with type 1 and type 2 diabetes (Jafari et al. 2016, Elseweidy et al. 2017, Hafez et al. 2019). The binding of vitamin D to its receptors regulates key genes involved in lipid metabolism. For example, vitamin D can increase the expression of PPAR-α and CPT-1. PPAR-α is expressed prominently in liver, heart and skeletal muscle and plays a key role in regulating genes that are involved in lipids storage and utilisation such as fatty acid oxidation. On the other hand, CPT-1 is a rate-limiting enzyme of β-oxidation of fatty acids, which takes place in the mitochondria. CPT-1 facilitates the first step of the transport of long-chain fatty acids into mitochondria (Lefebvre et al. 2006, Ning et al. 2015).
Systemic Amelioration via Curcumin in Rats following Splenectomy: Lipid Profile, Endothelial and Oxidative Damage
Published in Journal of Investigative Surgery, 2021
Yuksel Altinel, Emin Kose, Aysel Karacaglar, Serdar Demirgan, Volkan Sozer, Guven Ozkaya, Osman Bilgin Gulcicek, Gonul Simsek, Hafize Uzun
The lipid metabolism comprehends digestion and absorption in the liver, small intestine and transportation within lipoproteins via circulation regarding all the steps of the utilization and excretion of lipids [32]. The spleen might additionally affect the lipid metabolism in the intestine due to decreased lipid peroxidation following splenectomy [33] by inducing inflammatory processes and oxidative stress [34]. The total histopathological scores of the intestinal tissue of rats underwent splenectomy were significantly higher than L and SC groups regarding the increased number of infiltrating mononuclear cells (Table 5). The histological images showed the loss of enterocytes and moderate increases in the number of mononuclear cells in the intestinal lamina propria of splenectomized rats (Figure 2). However, SC group showed mildly increased number of mononuclear cells, suggesting an anti-inflammatory effect of curcumin on the intestinal tissue of rats underwent splenectomy.