Targeting SREBP-1-Mediated Lipogenesis as Potential Strategies for Cancer

Frontiers in Oncology, Journal Year: 2022, Volume and Issue: 12

Published: July 14, 2022

Sterol regulatory element binding protein-1 (SREBP-1), a transcription factor with basic helix–loop–helix leucine zipper, has two isoforms, SREBP-1a and SREBP-1c, derived from the same gene for regulating genes of lipogenesis, including acetyl-CoA carboxylase, fatty acid synthase, stearoyl-CoA desaturase. Importantly, SREBP-1 participates in metabolic reprogramming various cancers been biomarker prognosis or drug efficacy patients cancer. In this review, we first introduced structure, activation, key upstream signaling pathway SREBP-1. Then, potential targets molecular mechanisms SREBP-1-regulated lipogenesis types cancer, such as colorectal, prostate, breast, hepatocellular were summarized. We also discussed therapies targeting by small molecules, natural products, extracts herbs against tumor progression. This review could provide new insights understanding advanced findings about SREBP-1-mediated cancer its target therapeutics.

Language: Английский

---

Antioxidant Peptides from Monkfish Swim Bladders: Ameliorating NAFLD In Vitro by Suppressing Lipid Accumulation and Oxidative Stress via Regulating AMPK/Nrf2 Pathway

Marine Drugs, Journal Year: 2023, Volume and Issue: 21(6), P. 360 - 360

Published: June 16, 2023

In this study, we investigate the ameliorating functions of QDYD (MSP2), ARW (MSP8), DDGGK (MSP10), YPAGP (MSP13) and DPAGP (MSP18) from monkfish swim bladders on an FFA-induced NAFLD model HepG2 cells. The lipid-lowering mechanisms revealed that these five oligopeptides can up-regulate expression phospho-AMP-activated protein kinase (p-AMPK) proteins to inhibit sterol regulatory element binding protein-1c (SREBP-1c) increasing lipid synthesis up-regulating PPAP-α CPT-1 promoting β-oxidation fatty acids. Moreover, significantly reactive oxygen species' (ROS) production, promote activities intracellular antioxidases (superoxide dismutase, SOD; glutathione peroxidase, GSH-PX; catalase, CAT) bring down content malondialdehyde (MDA) derived peroxidation. Further investigations regulation oxidative stress was achieved through activating nuclear factor erythroid 2-related 2 (Nrf2) pathway raise levels heme oxygenase 1 (HO-1) downstream antioxidant proteases. Therefore, could serve as candidate ingredients develop functional products for treating NAFLD.

Language: Английский

---

Pathogenic mechanisms and regulatory factors involved in alcoholic liver disease

Journal of Translational Medicine, Journal Year: 2023, Volume and Issue: 21(1)

Published: May 4, 2023

Abstract Alcoholism is a widespread and damaging behaviour of people throughout the world. Long-term alcohol consumption has resulted in alcoholic liver disease (ALD) being leading cause chronic disease. Many metabolic enzymes, including dehydrogenases such as ADH, CYP2E1, CATacetaldehyde ALDHsand nonoxidative metabolizing enzymes SULT, UGT, FAEES, are involved metabolism ethanol, main component beverages. Ethanol changes functional or expression profiles various regulatory factors, kinases, transcription microRNAs. Therefore, underlying mechanisms ALD complex, involving inflammation, mitochondrial damage, endoplasmic reticulum stress, nitrification, oxidative stress. Moreover, recent evidence demonstrated that gut-liver axis plays critical role pathogenesis. For example, ethanol damages intestinal barrier, resulting release endotoxins alterations flora content bile acid metabolism. However, therapies show low effectiveness. this review summarizes pathways highly influential pathogenic factors pathology with aim new therapeutic insights.

Language: Английский

---

Pharmacologic inhibition of lipogenesis for the treatment of NAFLD

Journal of Hepatology, Journal Year: 2023, Volume and Issue: 80(2), P. 362 - 377

Published: Nov. 15, 2023

Language: Английский

---

Protein neddylation and its role in health and diseases

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: April 4, 2024

Abstract NEDD8 (Neural precursor cell expressed developmentally downregulated protein 8) is an ubiquitin-like that covalently attached to a lysine residue of substrate through process known as neddylation, catalyzed by the enzyme cascade, namely activating (E1), conjugating (E2), and ligase (E3). The substrates neddylation are categorized into cullins non-cullin proteins. Neddylation activates CRLs (cullin RING ligases), largest family E3 ligases, whereas alters their stability activity, well subcellular localization. Significantly, pathway and/or many abnormally activated or over-expressed in various human diseases, such metabolic disorders, liver dysfunction, neurodegenerative cancers, among others. Thus, targeting becomes attractive strategy for treatment these diseases. In this review, we first provide general introduction on its biochemical regulation, crystal structures enzymes complex with cullin substrates; then discuss how governs key biological processes via modification substrates. We further review literature data dysregulated several particularly cancer, followed outline current efforts discovery small molecule inhibitors promising therapeutic approach. Finally, few perspectives were proposed extensive future investigations.

Language: Английский

---

Protection Strategies Against Palmitic Acid-Induced Lipotoxicity in Metabolic Syndrome and Related Diseases

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(2), P. 788 - 788

Published: Jan. 18, 2025

Diets rich in carbohydrate and saturated fat contents, when combined with a sedentary lifestyle, contribute to the development of obesity metabolic syndrome (MetS), which subsequently increase palmitic acid (PA) levels. At high concentrations, PA induces lipotoxicity through several mechanisms involving endoplasmic reticulum (ER) stress, mitochondrial dysfunction, inflammation cell death. Nevertheless, there are endogenous strategies mitigate PA-induced its unsaturation elongation channeling storage lipid droplets (LDs), plays crucial role sequestering oxidized lipids, thereby reducing oxidative damage membranes. While extended exposure promotes reactive oxygen species (ROS) generation leading damage, acute ß-cells increases glucose-stimulated insulin secretion (GSIS), activation free fatty receptors (FFARs). Subsequently, FFARs by exogenous agonists has been suggested as potential therapeutic strategy prevent ß cells. Moreover, some acids, including oleic acid, can counteract negative impact on cellular health, suggesting complex interaction between different dietary fats outcomes. Therefore, challenge is peroxidation unsaturated acids utilization natural antioxidants. This complexity indicates necessity for further research into function diverse pathological conditions find main target against lipotoxicity. The aim this review is, therefore, examine recent data regarding mechanism underlying order identify that promote protection lipotoxicity, dysfunction apoptosis MetS obesity.

Language: Английский

---

FoxO1 as a tissue-specific therapeutic target for type 2 diabetes

Frontiers in Endocrinology, Journal Year: 2023, Volume and Issue: 14

Published: Oct. 23, 2023

Forkhead box O (FoxO) proteins are transcription factors that mediate many aspects of physiology and thus have been targeted as therapeutics for several diseases including metabolic disorders such type 2 diabetes mellitus (T2D). The role FoxO1 in metabolism has well studied, but recently FoxO1’s potential prevention therapy debated. For example, studies shown increased activity certain tissue types contributes to T2D pathology, symptoms, comorbidities, yet other elevated reported alleviate symptoms associated with diabetes. Furthermore, opposite effects active the same type. liver, by increasing hepatic glucose production. However, either increase or decrease lipogenesis adipogenesis white adipose tissue. In skeletal muscle, reduces uptake oxidation, promotes lipid increases muscle atrophy. While show lowers pancreatic insulin production secretion, others opposite, especially response oxidative stress inflammation. Elevated hypothalamus risk developing T2D. may mitigate Alzheimer’s disease, a neurodegenerative disease strongly Conversely, accumulating evidence implicates Parkinson’s pathogenesis. Here we review actions conditions tissues abundantly express highlight some current targeting treatment.

Language: Английский

---

Yellow leaf green tea modulates the AMPK/ACC/SREBP1c signaling pathway and gut microbiota in high‐fat diet‐induced mice to alleviate obesity

Journal of the Science of Food and Agriculture, Journal Year: 2024, Volume and Issue: 104(10), P. 5882 - 5895

Published: Feb. 26, 2024

Yellow leaf green tea (YLGT) is a new variety of Camellia sinensis (L.) O. Ktze, which has yellow leaves and the unique qualities 'three through three yellow'. The present study aimed to investigate anti-obesity effect YLGT in mice fed high-fat diet (HFD) explore potential mechanisms by regulating AMPK/ACC/SREBP1c signaling pathways gut microbiota.

Language: Английский

---

Reprogramming of Hepatic Metabolism and Microenvironment in Nonalcoholic Steatohepatitis

Annual Review of Nutrition, Journal Year: 2022, Volume and Issue: 42(1), P. 91 - 113

Published: May 19, 2022

Nonalcoholic fatty liver disease (NAFLD), a spectrum of metabolic associated with obesity, ranges from relatively benign hepatic steatosis to nonalcoholic steatohepatitis (NASH). The latter is characterized by persistent injury, inflammation, and fibrosis, which collectively increase the risk for end-stage diseases such as cirrhosis hepatocellular carcinoma. Recent work has shed new light on pathophysiology NAFLD/NASH, particularly role genetic, epigenetic, dietary factors dysfunctions in other tissues driving excess fat accumulation injury. In parallel, single-cell RNA sequencing studies have revealed unprecedented details molecular nature cell heterogeneity, intrahepatic cross talk, disease-associated reprogramming immune stromal vascular microenvironment. This review covers recent advances these areas, emerging concepts NASH pathogenesis, potential therapeutic opportunities.

Language: Английский

---

Effect of natural polysaccharides on alcoholic liver disease: A review

International Journal of Biological Macromolecules, Journal Year: 2023, Volume and Issue: 251, P. 126317 - 126317

Published: Aug. 16, 2023

Language: Английский

---