Diagnosis and Pathobiology
Franklyn De Silva, Jane Alcorn in The Elusive Road Towards Effective Cancer Prevention and Treatment, 2023
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].
Beneficial Lactic Acid Bacteria
K. Balamurugan, U. Prithika in Pocket Guide to Bacterial Infections, 2019
Lipid metabolism is the enzymatic break down of lipids into fatty acids and glycerol by lipases with either intracellular or extracellular localization in LAB strains. The latter are able to perform unique fatty acid transformation reactions, including isomerization, hydration, dehydration, and saturation (Hayek and Ibrahim 2013). Such products of lipid metabolism as conjugated fatty acids have beneficial effects on health, making them a target of intensive study. LAB were found to successfully produce conjugated linoleic acid (CLA) through two consecutive reactions: hydration of linoleic acid to 10-hydroxy-12-octadecenoic acid and dehydrating isomerization of the hydroxy fatty acid to CLA. Ricinoleic acid also can be transformed into CLA. On the other hand, linoleic acid can be used in production of conjugated trienoic acid through alkali-isomerization (Ogawa et al. 2005). Bifidobacterium species show ability to conduct isomerization of linoleic acid to CLA (Raimondi et al. 2016).
Diseases of the Nervous System
George Feuer, Felix A. de la Iglesia in Molecular Biochemistry of Human Disease, 2020
In conditions of adrenal hypofunction, the synthesis of protein in the brain is accelerated, and the total free amino acid concentration is markedly decreased with the exception of cysteic acid and glutathione which are increased. Adrenalectomy brings about reductions of glutamic acid, glutamine, GABA, taurine, valine, and cystine, whereas aspartic acid is unaltered. The decrease of GABA is important since this substance is an inhibitory mediator in the cortex and cerebellum. In contrast to hypofunction, it is expected that adrenal hyperfunction, administration of corticosteroids, and adrenocorticotrophic hormone decrease protein synthesis and increase breakdown. In particular, the conversion of glutamic acid to glutamine in human brain is prevented or reversed by deoxycorticosterone. Adrenocortical hormones elicit marked decreasing effects on GABA associated with reduced brain excitability. The effect of these conditions on lipid metabolism is not clear. Adrenocorticotrophic hormone and cortisol enhance brain phospholipid synthesis, and injection of cortisol or estradiol accelerates myelination and cerebroside content in various areas of the brain. The increased myelination and phospholipid production is associated with an enhanced functional development.
The role of pro-inflammatory cytokines in lipid metabolism of metabolic diseases
Published in International Reviews of Immunology, 2019
Yan Chen, Chun-Yan Yu, Wei-Min Deng
Lipids have been recognized as signaling molecules that have the capacity to trigger profound physiological responses [1]. According to the International Lipid Classification and Nomenclature Committee, lipids are currently classified into eight categories: (1) fatty acids; (2) glycerolipids; (3) glycerophospholipids; (4) sphingolipids; (5) sterol lipids; (6) prenol lipids; (7) saccharolipids; and (8) polyketides [2]. Lipid metabolism, is a complex process, including lipid uptake, transport, synthesis, and degradation [3]. Alteration of lipid metabolism leads to the changes of membrane compositions, protein distribution and functions, gene expression, and cellular functions, and further causes the development and progression of many diseases such as inflammation, hypertension, diabetes, liver disease, heart disease, renal disease, neurological disorder and cystic fibrosis [4]. Lipid abnormalities in critical illness include hypertriglyceridemia, increased levels of free fatty acids (FFA), decreased cholesterol-containing lipoproteins, lowdensity lipoprotein (LDL), and high-density lipoprotein (HDL) [5]. Adipose tissue, which consists of mainly adipocytes, nerve tissue and immune cells, has been considered as a crucial source of certain pro-inflammatory cytokines such as IL-1β, IL-6, TNF-α, etc. [6, 7]. Conversely, these pro-inflammatory cytokines are involved in regulating the proliferation and apoptosis of adipocytes, promoting lipolysis, inhibiting lipid synthesis and decreasing blood lipids, etc. Numerous studies have shown that inflammation and inflammatory cytokines are closely related to lipid metabolism.
Correlation of elevated levels of lipoprotein(a), high-density lipoprotein and low-density lipoprotein with severity of preeclampsia: a prospective longitudinal study
Published in Journal of Obstetrics and Gynaecology, 2020
Elena Konrad, Onur Güralp, Waleed Shaalan, Alaa A. Elzarkaa, Reham Moftah, Doaa Alemam, Eduard Malik, Amr A. Soliman
Significant physiological changes in lipid metabolism are observed during pregnancy. There is a substantial increase in triglyceride levels and a moderate increase in cholesterol levels resulting in hyperlipidaemia in the third trimester of pregnancy (Potter and Nestel 1979; Berge et al. 1996; Winkler et al. 2000). This provides a functional reservoir for the foetus to build cellular membranes (Hegele 1991; Ghio et al. 2011). Similarly, lipoprotein(a) levels increase during the course of pregnancy. Lipoprotein(a) is a component of blood lipids, acts as a cholesterol transporter, and plays an important role in lipid metabolism (Manten et al. 2003; Lippi et al. 2007). Biochemically, it is formed of a low-density lipoprotein (LDL) that is covalently bound to the carrier-protein apolipoprotein(a) that shows a high homology to plasminogen. By competitively binding to the plasminogen receptor, the effect of plasminogen is reduced; thus, lipoprotein(a) shows a prothrombotic effect (Miles et al. 1989; Utermann 1989). Elevated lipoprotein(a) levels are correlated with the development of preeclampsia and its severity (Aksoy et al. 2002; Mori et al. 2003).
Research progress of nanocarriers for gene therapy targeting abnormal glucose and lipid metabolism in tumors
Published in Drug Delivery, 2021
Xianhu Zeng, Zhipeng Li, Chunrong Zhu, Lisa Xu, Yong Sun, Shangcong Han
Decades ago, researchers discovered that tumor cells can synthesize lipids in the same manner as normal cells (Medes et al. 1953). Since then, studies have also found that abnormal increases in lipid metabolism have become an important hallmark of cancer (Santos & Schulze 2012). Lipid metabolism assays showed that compared with normal cells, cancer cells increased the expression of ATP-citrate lyase, acetyl coenzyme A (acetyl-CoA) carboxylase, and fatty acid (FA) synthase that is involved in de novo lipid synthesis (Bort et al. 2020). Lipid metabolism mainly includes de novo fatty acid synthesis, the triglyceride synthesis pathway, and fatty acid β-oxidation, which subsequently affect the proliferation, metabolism, and metastasis of cancer cells (as shown in Figure 2) (Vander Heiden et al. 2009).