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Responses of liver to acute and chronic physical activity
Published in Roy J. Shephard, Physical Activity and the Abdominal Viscera, 2017
Rodent investigations have provided insights into the molecular changes underlying training-induced changes in lipid and lipoprotein metabolism. Training reduces the hepatic levels of two enzymes central to the synthesis of fatty acids: acetyl-coenzyme A carboxylase and fatty acid synthase.[34, 258–260] Regular exercise also down-regulates the hepatic gene and protein content of stearoyl-CoA desaturase-1 (SCD-1), the rate-limiting enzyme in the biosynthesis of saturated-derived monounsaturated fats that are a major constituent of VLDL triglycerides. Further, there is a down-regulation of the microsomal triglyceride transfer protein that plays a key role in the assembly and secretion of VLDL lipoprotein,[261] and training increases levels of hepatic mRNA for the ATP-binding cassette transporter A-1 that plays a vital role in the membrane transport of HDL cholesterol and its remodeling in the plasma.[262]
Effects of Dietary Trans Fatty Acids on Cardiovascular Risk
Published in Nathalie Bergeron, Patty W. Siri-Tarino, George A. Bray, Ronald M. Krauss, Nutrition and Cardiometabolic Health, 2017
Ronald P. Mensink, Nathalie Bergeron, Patty W. Siri-Tarino, George A. Bray, Ronald M. Krauss
In the meta-analyses discussed earlier, the focus was on the relationship between the intakes of TFA with 18 carbon atoms and one single double bond. However, as discussed earlier, diets also provide minor amounts of other TFA. These intakes are even more difficult to estimate. Therefore, the most reliable estimate of intakes due to the low levels in the diet is to estimate levels in tissue lipid fractions. Still, it has to be acknowledged that TFA are metabolized in the human body and one TFA molecule can be converted into another TFA molecule. Vaccenic acid, for example, can be desaturated by a Δ9-desaturase (stearoyl-CoA desaturase-1), giving rise to the formation of a specific CLA isomer. Relationships between TFA in plasma lipids on CVD risk have been examined in several prospective cohort studies. In the Multi-Ethnic Study of Atherosclerosis cohort of 2837 U.S. adults, the proportion of trans-palmitoleic acid (trans-C16:1n-7) in the plasma phospholipid fraction was not related to incident CVD or CHD (de Oliveira Otto et al. 2013). In the Cardiovascular Health Study, a prospective cohort of older U.S. citizens, trans-isomers of linoleic acid in plasma phospholipids with two double bonds in the trans configuration were adversely related with total mortality, especially with CVD (Wang et al. 2014). The study cohort consisted of 2742 elderly individuals. No associations were observed for trans-monounsaturated fatty acids with 16 or 18 carbon atoms. Thus, these studies suggested that differences between the various TFA might exist, although further investigation and confirmation of these findings is needed.
Inhibiting Insulin Resistance and Accumulation of Triglycerides and Cholesterol in the Liver
Published in Christophe Wiart, Medicinal Plants in Asia for Metabolic Syndrome, 2017
Centella asiatica (L.) Urb. contains asiatic acid which given orally at a daily dose of 20 mg/kg for 45 days to streptozotocin-induced diabetic Wistar rats (glycaemia >250 mg/dL) 45 days lowered fluid and food intake, plasma cholesterol, triglycerides, increased high-density lipoprotein–cholesterol, lowered low-density lipoprotein–cholesterol, brought unesterified fatty acids close to normal, and lowered atherogenic index.365 At the hepatic level, this triterpene normalized cholesterol, triglycerides, and unesterified fatty acids.365 Asiatic acid increased the activity of plasma lipoprotein lipase, which catalyze the endothelial release of fatty acids from very low-density lipoprotein triglycerides, lecithin cholesterol acyltransferase which esterifies cholesterol in high-density lipoprotein, and decreased hepatic 3-hydroxy-3-methylglutaryl-coenzyme A reductase.365 In a parallel study, asiatic acid (Figure 3.26) given to C57BL/6 mice on high-fat diet at a dose of 20 mg/kg/day for 7 weeks decreased body weight gain, food intake, liver weight, and epididymal fats. The treatment decreased plasma triglycerides and cholesterol, had no effect on plasma glucose, decreased plasma insulin and decreased insulin resistance, and had no effect on plasma adiponectin nor leptin.366 At the hepatic level, this triterpene decreased cholesterol from 7.6 to 6.4 mg/g and triglycerides from 64.5 to 38.2 mg/g.366 This regimen increased fecal lipids from 13.6 to 15.7 mg/g feces.366 At the hepatic level, asiatic acid decreased the expression of acetyl-CoA carboxylase fatty acid, synthetase stearoyl-CoA desaturase-1366 which are targets of sterol regulatory element-binding protein-1c. This regimen decreased hepatic reactive oxygen species, increased glutathione as well as the activity of catalase and glutathione peroxidase.366 This treatment decreased serum aspartate aminotransferase, improved hepatic cytoarchitecture with decreased hepatic triglycerides droplets.366 This triterpene decreased hepatic expression of nuclear factor-κB and the levels of interleukin-6, interleukin-1β and tumor necrosis factor-α.366 The precise hypolipidemic mode of action of asiatic acid is apparently unknown and could result, at least, from increased hepatic insulin sensitivity hence increased expression of sterol regulatory element-binding protein-1c and downstream targets.
Targeting stearoyl-coa desaturase enhances radiation induced ferroptosis and immunogenic cell death in esophageal squamous cell carcinoma
Published in OncoImmunology, 2022
Hui Luo, Xiaohui Wang, Shuai Song, Yunhan Wang, Qinfu Dan, Hong Ge
Recently, Jessalyn et al. revealed that oleic acid (OA) from lymph nodes contributed to reduced ferroptosis in tumor cells.18 OA is an omega-9 fatty acid that belongs to the monounsaturated fatty acids family.19 Stearoyl-CoA desaturase (SCD1) has been described as a crucial endoplasmic reticulum enzyme responsible for converting saturated fatty acid (palmitic acid (PA) and stearic acid (SA)) to monounsaturated fatty acid (OA and palmitoleic acid (POA)).20,21 Impairment of lipid metabolism usually increases ferroptotic cell death.22 In several malignant tumors, SCD1 was necessary for maintain cell viability and stemness of cancer stem cells.23 Moreover, there were a few studies demonstrating the immunogenicity of ferroptosis in which dying tumor cells promoted the maturation of immune cells.24,25 Therefore, we hypothesized that upregulation of SCD1 was capable of altering monounsaturated fatty acid metabolism, representing an intrinsic cytoprotective mechanism against radiation-induced ferroptosis in tumor cells.
The effect of simvastatin on gene expression of low-density lipoprotein receptor, sterol regulatory element-binding proteins, stearoyl-CoA desaturase 1 mRNA in rat hepatic tissues
Published in Archives of Physiology and Biochemistry, 2022
Abbas Nezhadebrahimi, Hamid Sepehri, Mehrdad Jahanshahi, Majid Marjani, Abdoljalal Marjani
Stearoyl-CoA desaturase 1 (SCD1) is an enzyme that synthesis the monounsaturated fatty acids (MUFA) from saturated fatty acids. The enzyme plays an important role in the regulation of fatty acid metabolism (Ntambi 1999). Monounsaturated fatty acids act as mediators of signal transduction and cellular differentiation (Zhang et al. 1999). The SCD expression can affect membrane fluidity, lipid metabolism, and adiposity (Ntambi 1999). The SCD activity seems to be mediated by SREBP-1. Studies on mice have been shown that expressing SREBP-1 has increased expression of SCD and vice versa. SCD increased the synthesis of MUFA, while knockout of SREBT-1 leads to a decrease in SCD expression (Shimomura et al. 1998, Liang et al. 2002). According to different findings, we planned to choose different dosage of simvastatin and study their effect on some chosen parameters. We tried to reduce the side effect and toxicity of simvastatin. Thus, the study aimed to assess the effect of different dosages of simvastatin on gene expression of low-density lipoprotein receptor (LDLR), sterol regulatory element-binding proteins (SREBPs), stearoyl-CoA desaturase 1 (SCD1) mRNA in rat hepatic tissues fed with high-fat diets and its association with some biochemical parameters.
Testosterone treatment improves liver function and reduces cardiovascular risk: A long-term prospective study
Published in Arab Journal of Urology, 2021
Ahmad Al-Qudimat, Raed M. Al-Zoubi, Aksam A. Yassin, Mustafa Alwani, Omar M. Aboumarzouk, Khaled AlRumaihi, Raidh Talib, Abdulla Al Ansari
The role of TTh in reducing expression of acetyl-CoA carboxylase α (Acaca), fatty acid synthase (Fasn) and sterol regulatory element-binding transcription factor 1 (Srebf1) genes involved in hepatic lipid assembly and secretion is well-established [37,38,59]. It has also been hypothesised that androgens could modulate liver fatty acid β-oxidation and lipid synthesis via regulation of SREBF-1 c, a key regulator of fatty acid synthesis, and its primary target gene stearoyl-CoA desaturase (SCD1) that catalyses the rate-limiting step in the synthesis monounsaturated fatty acids [57]. In addition to this hypothesis, orchidectomised rats were treated with dihydrotestosterone and an association was found with lower lipid accumulation by decreasing fatty acid, cholesterol synthesis, and increasing β-oxidation [60]. Nevertheless, these mechanistic have only recently arisen, and the validity of these findings from animal studies and the relationship between low testosterone levels and hepatic steatosis in humans requires further studies assessing biopsy samples in TTh clinical trials.