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https://www.readbyqxmd.com/read/28645211/akr1c3-mediated-adipose-androgen-generation-drives-lipotoxicity-in-women-with-polycystic-ovary-syndrome
#1
Michael W O'Reilly, Punith Kempegowda, Mark Walsh, Angela E Taylor, Konstantinos N Manolopoulos, J William Allwood, Robert K Semple, Daniel Hebenstreit, Warwick B Dunn, Jeremy W Tomlinson, Wiebke Arlt
Context: Polycystic ovary syndrome (PCOS) is a prevalent metabolic disorder, occurring in up to 10% of women of reproductive age. PCOS is associated with insulin resistance and cardiovascular risk. Androgen excess is a defining feature of PCOS and has been suggested as causally associated with insulin resistance; however, mechanistic evidence linking both is lacking. We hypothesized that adipose tissue is an important site linking androgen activation and metabolic dysfunction in PCOS...
June 22, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28637103/-the-development-of-hepatocellular-carcinoma-in-non-alcoholic-fatty-liver-disease
#2
REVIEW
Oh Sang Kwon, Joon Hwan Kim, Ju Hyun Kim
Non-alcoholic fatty liver disease (NAFLD) may be one of the important causes of cryptogenic hepatocellular carcinoma (HCC). NAFLD-related HCCs (NAFLD-HCCs) have the following clinical features: high body mass index, deranged lipid profiles, diabetes mellitus, hypertension, and metabolic syndrome. Among them, obesity, diabetes mellitus, and high Fe contents in the liver are risk factors of developing HCC in patients with NAFLD. Inflammatory cytokines, adipokines, insulin like growth factor-I, and lipotoxicity are intermingled and may cross react with each other to develop HCC...
June 25, 2017: Korean Journal of Gastroenterology, Taehan Sohwagi Hakhoe Chi
https://www.readbyqxmd.com/read/28637102/-the-progression-of-liver-fibrosis-in-non-alcoholic-fatty-liver-disease
#3
REVIEW
Moon Young Kim
Understanding the pathogenesis of non-alcoholic steatohepatitis (NASH) and its fibrosis progression is still evolving. Nonetheless, current evidence suggests that mechanisms involved are very complex parallel processes with multiple metabolic factors. Lipotoxicity related with excess saturated free fatty acids, obesity, and insulin resistance acts as the central driver of cellular injury via oxidative stress. Hepatocyte apoptosis and/or senescence are also contribute to the activation of inflammasome via various intra- and inter-cellular signaling mechanisms that lead to fibrosis...
June 25, 2017: Korean Journal of Gastroenterology, Taehan Sohwagi Hakhoe Chi
https://www.readbyqxmd.com/read/28635632/glucose-and-lipid-dysmetabolism-in-a-rat-model-of-prediabetes-induced-by-a-high-sucrose-diet
#4
Ana Burgeiro, Manuela G Cerqueira, Bárbara M Varela-Rodríguez, Sara Nunes, Paula Neto, Frederico C Pereira, Flávio Reis, Eugénia Carvalho
Glucotoxicity and lipotoxicity are key features of type 2 diabetes mellitus, but their molecular nature during the early stages of the disease remains to be elucidated. We aimed to characterize glucose and lipid metabolism in insulin-target organs (liver, skeletal muscle, and white adipose tissue) in a rat model treated with a high-sucrose (HSu) diet. Two groups of 16-week-old male Wistar rats underwent a 9-week protocol: HSu diet (n = 10)-received 35% of sucrose in drinking water; Control (n = 12)-received vehicle (water)...
June 21, 2017: Nutrients
https://www.readbyqxmd.com/read/28633867/review-of-a-causal-role-of-fructose-containing-sugars-in-myocardial-susceptibility-to-ischemia-reperfusion-injury
#5
REVIEW
Gerald J Maarman, Amy E Mendham, Kim Lamont, Cindy George
In 2012, the World Health Organization Global Status Report on noncommunicable diseases showed that 7.4 million deaths were due to ischemic heart disease. Consequently, cardiovascular disease is a significant health burden, especially when partnered with comorbidities such as obesity, metabolic syndrome, and type 2 diabetes mellitus. Of note, these diseases can all be induced or exacerbated by diet. Carbohydrates, in particular, fructose and glucose, generally form the largest part of the human diet. Accumulating evidence from animal studies suggests that if large amounts of fructose are consumed either in isolation or in combination with glucose (fructose-containing sugars), myocardial susceptibility to ischemia/reperfusion (I/R) injury increases...
June 2017: Nutrition Research
https://www.readbyqxmd.com/read/28625088/mitochondrial-content-and-hepcidin-are-increased-in-obese-pregnant-mothers
#6
G M Anelli, M Cardellicchio, C Novielli, P Antonazzo, M I Mazzocco, I Cetin, C Mandò
OBJECTIVE: Maternal obesity is characterized by systemic low-grade inflammation and oxidative stress (OxS) with the contribution of fetal sex dimorphism. We recently described increased mitochondrial content (mtDNA) in placentas of obese pregnancies. Here we quantify mtDNA and hepcidin as indexes of OxS and systemic inflammation in the obese maternal circulation. METHODS: Forty-one pregnant women were enrolled at elective Caesarean section: 16 were normal-weight [NW] and 25 were obese (OB)...
June 18, 2017: Journal of Maternal-fetal & Neonatal Medicine
https://www.readbyqxmd.com/read/28612562/-pancreatic-%C3%AE-cell-dysfunction-and-apoptosis-induced-by-elevated-free-fatty-acids-synergize-with-hyperglycemia
#7
Hui-Wen Tan, Nai-Qian Zhao, Ye-Rong Yu, Li-Na Han, Xiang-Xun Zhang
OBJECTIVES: To analysis the effects of glucoxicity and lipotoxicity on the function and apoptosis of pancreatic β-cells. METHODS: The levels of circulating glucose and free fat acids (FFAs) were elevated by infusion dextrose and fat emulsion in high-fat obese rats. The insulin resistance model obese rats were divided into four gourp: obese group with saline infusion (OB-NS group, n=7), obese group with glucose infusion (OB-GS group, n=9), obese group with Lipid emulsion infusion (OB-FFA group, n=8), obese group with glucose and lipid emulsion infusion (OB-FG group, n=9)...
January 2017: Sichuan da Xue Xue Bao. Yi Xue Ban, Journal of Sichuan University. Medical Science Edition
https://www.readbyqxmd.com/read/28604676/cholesterol-and-fatty-acids-regulate-cysteine-ubiquitylation-of-acat2-through-competitive-oxidation
#8
Yong-Jian Wang, Yan Bian, Jie Luo, Ming Lu, Ying Xiong, Shu-Yuan Guo, Hui-Yong Yin, Xu Lin, Qin Li, Catherine C Y Chang, Ta-Yuan Chang, Bo-Liang Li, Bao-Liang Song
Ubiquitin linkage to cysteine is an unconventional modification targeting protein for degradation. However, the physiological regulation of cysteine ubiquitylation is still mysterious. Here we found that ACAT2, a cellular enzyme converting cholesterol and fatty acid to cholesteryl esters, was ubiquitylated on Cys277 for degradation when the lipid level was low. gp78-Insigs catalysed Lys48-linked polyubiquitylation on this Cys277. A high concentration of cholesterol and fatty acid, however, induced cellular reactive oxygen species (ROS) that oxidized Cys277, resulting in ACAT2 stabilization and subsequently elevated cholesteryl esters...
June 12, 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/28588189/metabolic-injury-induced-nlrp3-inflammasome-activation-dampens-phospholipid-degradation
#9
Elena Rampanelli, Evelyn Orsó, Peter Ochodnicky, Gerhard Liebisch, Pieter J Bakker, Nike Claessen, Loes M Butter, Marius A van den Bergh Weerman, Sandrine Florquin, Gerd Schmitz, Jaklien C Leemans
The collateral effects of obesity/metabolic syndrome include inflammation and renal function decline. As renal disease in obesity can occur independently of hypertension and diabetes, other yet undefined causal pathological pathways must be present. Our study elucidate novel pathological pathways of metabolic renal injury through LDL-induced lipotoxicity and metainflammation. Our in vitro and in vivo analysis revealed a direct lipotoxic effect of metabolic overloading on tubular renal cells through a multifaceted mechanism that includes intralysosomal lipid amassing, lysosomal dysfunction, oxidative stress, and tubular dysfunction...
June 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28587303/the-role-of-lipid-and-lipoprotein-metabolism-in-non-alcoholic-fatty-liver-disease
#10
REVIEW
Francesco Massimo Perla, Maurizia Prelati, Michela Lavorato, Daniele Visicchio, Caterina Anania
Due to the epidemic of obesity across the world, nonalcoholic fatty liver disease (NAFLD) has become one of the most prevalent chronic liver disorders in children and adolescents. NAFLD comprises a spectrum of fat-associated liver conditions that can result in end-stage liver disease and the need for liver transplantation. Simple steatosis, or fatty liver, occurs early in NAFLD and may progress to nonalcoholic steatohepatitis, fibrosis and cirrhosis with increased risk of hepatocellular carcinoma. The mechanism of the liver injury in NAFLD is currently thought to be a "multiple-hit process" where the first "hit" is an increase in liver fat, followed by multiple additional factors that trigger the inflammatory activity...
June 6, 2017: Children
https://www.readbyqxmd.com/read/28586518/combination-therapy-with-multiple-oral-hypoglycaemic-agents-together-with-short-term-basal-insulin-in-new-onset-type-2-diabetes-mellitus-with-marked-hyperglycaemia
#11
S Ray, J J Mukherjee
Type 2 diabetes mellitus is characterized by the relentless loss of β-cell function, which is partly attributable to glucotoxicity and lipotoxicity. Prolonged exposure to excess glucose and oxidative stress leads to β-cell destruction [1,2]. Evidence suggests that early intensive intervention to achieve normoglycaemia can preserve β-cell function, probably by correcting glucotoxicity and lipotoxicity [3]. This article is protected by copyright. All rights reserved.
June 6, 2017: Diabetic Medicine: a Journal of the British Diabetic Association
https://www.readbyqxmd.com/read/28586412/high-fat-diet-and-female-fertility
#12
Natalie M Hohos, Malgorzata E Skaznik-Wikiel
The prevalence of obesity is high among reproductive age women and is associated with impaired reproductive function. Obesity is multifactorial in origin, yet many cases of obesity result from overconsumption of a diet high in fat. Excess dietary fat increases both adipose and non-adipose tissue lipid content, and through lipotoxicity leads to cell dysfunction and death. High dietary fat intake, with or without the development of obesity, impairs female hypothalamic-pituitary-ovarian (HPO) axis functionality and fertility...
June 6, 2017: Endocrinology
https://www.readbyqxmd.com/read/28585218/lipotoxicity-in-obesity-benefit-of-olive-oil
#13
Saad Elias, Sbeit Wisam, Arraf Luai, Barhoum Massad, Assy Nimer
The clinical implication of Lipotoxicity in obesity derives primarily from its potential to progress to insulin resistance, endothelial dysfunction and atherosclerosis. Olive oil rich diet decrease accumulation of triglyceride in the liver, improved postprandial triglyceride levels, improve glucose and GLP-1 response in insulin resistant subjects, and up regulate GLUT-2 expression in the liver. The exact molecular mechanism is unknown but, decreasing NFkB activation, decreasing LDL oxidation and improving insulin resistance by less production of inflammatory cytokines (TNF-a, IL-6) and improvement of kinases JNK-mediated phosphorylation of IRS-1 are the principle mechanisms...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28585213/microrna-and-adipogenesis
#14
Ayse Basak Engin
In obesity, the process of adipogenesis largely determines the number of adipocytes in body fat depots. Adipogenesis is regulated by several adipocyte-selective microRNAs (miRNAs) and transcription factors that modulate adipocyte proliferation and differentiation. However, some miRNAs block expression of master regulators of adipogenesis. Additionally, specific miRNAs have been implicated in adipocyte differentiation and mature adipocyte functions. While, each miRNA targets multiple mRNAs, which may coordinate or antagonize each other's functions, several miRNAs are dysregulated in other tissues during obesity-related comorbidities...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28585212/lipotoxicity-related-hematological-disorders-in-obesity
#15
Ibrahim Celalettin Haznedaroglu, Umit Yavuz Malkan
Lipotoxicity can mediate endothelial dysfunction in obesity. Altered endothelial cell phenotype during the pathobiological course of the lipotoxicity may lead to the hemostatic abnormalities, which is a hallmark of several hematological disorders. Impaired hemostasis could also be directly related to the numerous metabolic diseases such as hypertension, diabetes and atherosclerosis. On the other hand, local hematopoietic bone marrow (BM) renin-angiotensin system (RAS) contributes to the development of atherosclerosis via acting on the lipotoxicity processes...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28585211/non-alcoholic-fatty-liver-disease
#16
Atilla Engin
Non-alcoholic fatty liver disease (NAFLD) is in parallel with the obesity epidemic and it is the most common cause of liver diseases. The development of hepatic steatosis in majority of patients is linked to dietary fat ingestion. NAFLD is characterized by excess accumulation of triglyceride in the hepatocyte due to both increased inflow of free fatty acids and de novo hepatic lipogenesis. Insulin resistance with the deficiency of insulin receptor substrate-2 (IRS-2)-associated phosphatidylinositol 3-kinase (PI3K) activity causes an increase in intracellular fatty acid-derived metabolites such as diacylglycerol, fatty acyl CoA or ceramides...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28585204/insulin-resistance-obesity-and-lipotoxicity
#17
Dilek Yazıcı, Havva Sezer
Lipotoxicity , originally used to describe the destructive effects of excess fat accumulation on glucose metabolism, causes functional impairments in several metabolic pathways, both in adipose tissue and peripheral organs, like liver, heart, pancreas and muscle. Lipotoxicity has roles in insulin resistance and pancreatic beta cell dysfunction. Increased circulating levels of lipids and the metabolic alterations in fatty acid utilization and intracellular signaling, have been related to insulin resistance in muscle and liver...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28585202/microbiota-and-lipotoxicity
#18
Evren Doruk Engin
Obesity and metabolic syndrome is a multisystemic disorder, that is characterized by excess caloric intake and spillover lipotoxicity caused by ectopic lipid accumulation in non-adipose tissues. Low grade chronic inflammation and insulin resistance are the hallmarks of the disorder, which further aggravate the condition. Gut microbiota constitutes an indispensible part of human superorganism's energy harvesting apparatus. The dynamic composition of microbiota changes with age, life style and host metabolic background...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28585200/what-is-lipotoxicity
#19
Ayse Basak Engin
Enlarged fat cells in obese adipose tissue diminish capacity to store fat and are resistant to the anti-lipolytic effect of insulin. Insulin resistance (IR)-associated S-nitrosylation of insulin-signaling proteins increases in obesity. In accordance with the inhibition of insulin-mediated anti-lipolytic action, plasma free fatty acid (FFA) levels increase. Additionally, endoplasmic reticulum stress stimuli induce lipolysis by activating cyclic adenosine monophosphate/Protein kinase A (cAMP/PKA) and extracellular signal-regulated kinase ½ (ERK1/2) signaling in adipocytes...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28585199/adipose-tissue-function-and-expandability-as-determinants-of-lipotoxicity-and-the-metabolic-syndrome
#20
Stefania Carobbio, Vanessa Pellegrinelli, Antonio Vidal-Puig
The adipose tissue organ is organised as distinct anatomical depots located all along the body axis and it is constituted of three different types of adipocytes : white, beige and brown which are integrated with vascular, immune, neural and extracellular stroma cells. These distinct adipocytes serve different specialised functions. The main function of white adipocytes is to ensure healthy storage of excess nutrients/energy and its rapid mobilisation to supply the demand of energy imposed by physiological cues in other organs, whereas brown and beige adipocytes are designed for heat production through uncoupling lipid oxidation from energy production...
2017: Advances in Experimental Medicine and Biology
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