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Qian Chen, Mengyang Liu, Haiyang Yu, Jian Li, Sijian Wang, Yi Zhang, Feng Qiu, Tao Wang
Scutellaria baicalensis has been reported to improve the lipid metabolism of high-fat diet-induced liver dysfunction, but direct evidence is rare. This study aimed to explore the effects and mechanisms of S. baicalensis and its major constituent baicalin on hepatic lipotoxicity. KK-Ay mice and orotic acid (OA)-induced nonalcoholic fatty liver disease (NAFLD) rats were used to evaluate lipid metabolism regulatory effects. Sodium oleate-induced triglyceride-accumulated HepG2 cells were used for the mechanism study, pretreated with or without compound C or STO-609 or transfected with liver kinase B1 (LKB1) siRNA...
March 14, 2018: Journal of Natural Medicines
Consolacion Garcia-Contreras, Marta Vazquez-Gomez, Laura Torres-Rovira, Jorge Gonzalez, Esteban Porrini, Magali Gonzalez-Colaço, Beatriz Isabel, Susana Astiz, Antonio Gonzalez-Bulnes
Sarcopenia and sarcopenic obesity are currently considered major global threats for health and well-being. However, there is a lack of adequate preclinical models for their study. The present trial evaluated the suitability of aged swine by determining changes in adiposity, fatty acids composition, antioxidant status and lipid peroxidation, development of metabolic disturbances and structural changes in tissues and organs. Iberian sows with clinical evidence of aging-related sarcopenia were fed a standard diet fulfilling their maintenance requirements or an obesogenic diet for 100 days...
March 12, 2018: International Journal of Molecular Sciences
Kung-Yen Chen, Jui-An Lin, Han-Yun Yao, An-Chih Hsu, Yu-Ting Tai, Jui-Tai Chen, Mao-Chih Hsieh, Tang-Long Shen, Ren-Yi Hsu, Hong-Tan Wu, Guey Horng Wang, Bing-Ying Ho, Yu-Pei Chen
Arctigenin (ATG), a lignin extracted from Arctium lappa (L.), exerts antioxidant and anti-inflammatory effects. We hypothesized that ATG exerts a protective effect on hepatocytes by preventing nonalcoholic fatty liver disease (NAFLD) progression associated with lipid oxidation-associated lipotoxicity and inflammation. We established an in vitro NAFLD cell model by using normal WRL68 hepatocytes to investigate oleic acid (OA) accumulation and the potential bioactive role of ATG. The results revealed that ATG inhibited OA-induced lipid accumulation, lipid peroxidation, and inflammation in WRL68 hepatocytes, as determined using Oil Red O staining, thiobarbituric acid reactive substance assay, and inflammation antibody array assays...
February 11, 2018: Nutrition Research
Lifang Guo, Minggang Tian, Ruiqing Feng, Ge Zhang, Ruoyao Zhang, Xuechen Li, Zhiqiang Liu, Xiuquan He, Jing Zhi Sun, Xiaoqiang Yu
Lipid droplets (LDs) with own interface architecture not only play crucial roles in protecting cell from lipotoxicity and lipoapoptosis but also closely relate with many diseases such as fatty liver and diabetes. Thus, as one of important applied biomaterials, fluorescent probes with ultrahigh selectivity for in-situ and high-fidelity imaging LDs in living cells and tissues are critical to elucidate relevant physiological and pathological events as well as detect related diseases. However, available LDs probes only utilizing their waterless neutral cores but ignoring the unique phospholipid monolayer interfaces exhibit low selectivity...
March 9, 2018: ACS Applied Materials & Interfaces
A R Ramirez, O L Acosta, M B Maya, M El-Hafidi
In metabolic diseases such as obesity, metabolic syndrome and type II diabetes, the over-expression of uncoupling proteins (UCPs) in a response to increased reactive oxygen species (ROS) generation by mitochondrial respiratory complexes, and to the excess of free fatty acid (FFA) supply from adipose tissue, may protect cells from oxidative stress, lipotoxicity and in turn from death. UCPs by reducing superoxide anion and H2O2 generation trigger several signals to cell for their adaptation to the lipotoxic microenvironment...
March 7, 2018: Current Molecular Medicine
Iris Ginés, Katherine Gil-Cardoso, Joan Serrano, Àngela Casanova-Martí, MTeresa Blay, Montserrat Pinent, Anna Ardévol, Ximena Terra
Obesity is highly associated with the pathologies included in the concept of the Metabolic Syndrome. Grape-seed proanthocyanins (GSPE) have showed very positive effects against all these metabolic disruptions; however, there is, as yet, no consensus about their effectiveness against an obesogenic challenge, such as a cafeteria diet. We determined the effectiveness of a dose of 500 mg GSPE/kg b.w. (body weight) against the obesogenic effects of a 17-week cafeteria diet, administered as a sub-chronic treatment, 10-15 days before, intermittently and at the end of the diet, in Wistar rats...
March 7, 2018: Nutrients
Stanley M Walls, Anthony Cammarato, Dale A Chatfield, Karen Ocorr, Greg L Harris, Rolf Bodmer
Lipotoxic cardiomyopathy (LCM) is characterized by abnormal myocardial accumulation of lipids, including ceramide; however, the contribution of ceramide to the etiology of LCM is unclear. Here, we investigated the association of ceramide metabolism and ceramide-interacting proteins (CIPs) in LCM in the Drosophila heart model. We find that ceramide feeding or ceramide-elevating genetic manipulations are strongly associated with cardiac dilation and defects in contractility. High ceramide-associated LCM is prevented by inhibiting ceramide synthesis, establishing a robust model of direct ceramide-associated LCM, corroborating previous indirect evidence in mammals...
March 6, 2018: Cell Reports
Takwa Bedhiafi, Kamel Charradi, Mouna Ben Azaiz, Mohamed Mahmoudi, Issam Msakni, Khawla Jebari, Ammar Bouziani, Ferid Limam, Ezzedine Aouani
Spleen is the largest lymphoid organ and obesity is related to an elevated risk of immunity dysfunction and the mechanism whereby fat adversely affects the spleen is poorly understood. This study was designed to assess the effectiveness of grape seed and skin extract (GSSE) and orlistat (Xenical, Xe) on high fat diet (HFD)-induced spleen lipotoxicity. Obese rats were treated either with GSSE (4 g/kg bw) or Xe (2 mg/kg bw) or GSSE + Xe and monitored for weight loss during 3 months. Animals were then sacrificed and their spleen used for the evaluation of lipotoxicity-induced oxidative stress and inflammation as well as the putative protection afforded by GSSE and Xe treatment...
March 7, 2018: Applied Physiology, Nutrition, and Metabolism, Physiologie Appliquée, Nutrition et Métabolisme
Huimin Jin, Cheng Yan, Tengfei Xiao, Nannan Yan, Jie Xu, Liping Zhou, Xiaoming Zhou, Qixiang Shao, Sheng Xia
Diets rich in n-3 polyunsaturated fatty acid (n-3 PUFA) fish oil (FO) have beneficial effects in obesity‑associated metabolic disease. However, contradictory roles in inflammatory disease intervention have been reported. Our previous work revealed that a high‑FO diet promoted myeloid cell differentiation by modifying the bone marrow microenvironment; however, its effects on liver inflammation and complement system activation remain unknown. By performing ELISA, reverse transcription‑quantitative polymerase chain reaction, flow cytometry and histology on mice fed with high‑FO and low‑fat diets, the present study demonstrated that a 4‑week high‑FO diet promoted liver inflammation in mice without affecting body or liver weight...
March 6, 2018: Molecular Medicine Reports
Gong Deuk Bae, Eun-Young Park, Dong Jae Baek, Hee-Sook Jun, Oh Yoon Sin
Liquiritigenin (LQ) is a major active component of licorice root, which is a flavone used for treating many diseases, including diabetes. LQ has been shown to exhibit a glucose-lowering effect in diabetic mice. Therefore, we investigated the potential of LQ to protect against lipotoxicity-induced beta-cell apoptosis and the underlying molecular mechanisms. Exposure of INS-1 rat insulinoma cells to LQ significantly increased cell viability and blocked palmitate (PA)-induced apoptosis, as evidenced by the reduction of Annexin-V-stained cells, cleaved caspase-3 levels, and poly (ADP-ribose) polymerase (PARP) activity, as well as upregulation of Bcl-2 expression...
February 27, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Hideaki Inoue, Jun Shirakawa, Yu Togashi, Kazuki Tajima, Tomoko Okuyama, Mayu Kyohara, Yui Tanaka, Kazuki Orime, Yoshifumi Saisho, Taketo Yamada, Kimitaka Shibue, Rohit N Kulkarni, Yasuo Terauchi
Chronic low-grade inflammation in the pancreatic islets is observed in individuals with type 2 diabetes, and macrophage levels are elevated in the islets of these individuals. However, the molecular mechanisms underlying the interactions between the pancreatic β-cells and macrophages and their involvement in inflammation are not fully understood. Here, we investigated the role of S100 calcium-binding protein A8 (S100A8), a member of damage-associated molecular pattern molecules (DAMPs) in β-cell inflammation...
March 1, 2018: Journal of Biological Chemistry
Lakshman Singh, Sonia Tyagi, Damian Myers, Gustavo Duque
PURPOSE OF REVIEW: Bone marrow fat expresses mixed characteristics, which could correspond to white, brown, and beige types of fat. Marrow fat could act as either energy storing and adipokine secreting white fat or as a source of energy for hematopoiesis and bone metabolism, thus acting as brown fat. However, there is also a negative interaction between marrow fat and other elements of the bone marrow milieu, which is known as lipotoxicity. In this review, we will describe the good and bad roles of marrow fat in the bone, while focusing on the specific components of the negative effect of marrow fat on bone metabolism...
February 23, 2018: Current Osteoporosis Reports
Takayuki Tatsumi, Kaori Takayama, Shunsuke Ishii, Atsushi Yamamoto, Taichi Hara, Naojiro Minami, Naoyuki Miyasaka, Toshiro Kubota, Akira Matsuura, Eisuke Itakura, Satoshi Tsukamoto
Although autophagy is classically viewed as a non-selective degradation system, recent studies have revealed that various forms of selective autophagy also play crucial physiological roles. However, the induction of selective autophagy is not well understood. In this study, we established a forced selective autophagy system using a fusion of an autophagy adaptor and a substrate-binding protein. In both mammalian cells and fertilized mouse embryos, efficient forced lipophagy was induced by expression of a fusion of p62 (Sqstm1) and a lipid droplet (LD)-binding domain...
February 23, 2018: Development
Amalie Ribel-Madsen, Rasmus Ribel-Madsen, Kristian Fog Nielsen, Susanne Brix, Allan A Vaag, Charlotte Brøns
Low birth weight (LBW) individuals have an increased risk of developing insulin resistance and type 2 diabetes compared with normal birth weight (NBW) individuals. We hypothesised that LBW individuals exhibit an increased fatty acid flux into lipogenesis in non-adipose tissue with a resulting accumulation of lipotoxic lipids, including ceramides, in the blood. Therefore, we measured fasting plasma levels of 27 ceramides in 18 young, healthy, LBW men and 25 NBW controls after an isocaloric control diet and a 5-day high-fat, high-calorie diet by HPLC-HRMS...
February 22, 2018: Scientific Reports
Sun Ryoung Choi, Ji Hee Lim, Min Young Kim, Eun Nim Kim, Yaeni Kim, Beom Soon Choi, Yong-Soo Kim, Hye Won Kim, Kyung-Min Lim, Min Jeong Kim, Cheol Whee Park
BACKGROUND: Adiponectin is known to take part in the regulation of energy metabolism. AdipoRon, an orally-active synthetic adiponectin agonist, binds to both adiponectin receptors (AdipoR)1/R2 and ameliorates diabetic complications. Among the lipid metabolites, the ceramide subspecies of sphingolipids have been linked to features of lipotoxicity, including inflammation, cell death, and insulin resistance. We investigated the role of AdipoRon in the prevention and development of type 2 diabetic nephropathy...
February 17, 2018: Metabolism: Clinical and Experimental
Qiao Wang, Xiuxiu Du, Ke Ma, Ping Shi, Wenbin Liu, Jing Sun, Min Peng, Zhiwei Huang
Elongases FEN1/ELO2 and SUR4/ELO3 are important enzymes involved in the elongation of long-chain fatty acids (LCFAs) to very long-chain fatty acids (VLCFAs) in Saccharomyces cerevisiae. The molecular mechanism of the involvement of these elongases in lipotoxicity is unclear. In the present study, we investigated the role of VLCFA elongases in oleic acid-mediated yeast cytotoxicity. The spot test showed that yeast strains with the deletion of ELO2 or ELO3 were strikingly sensitive to oleic acid, while there was no change on the growth of strain with deleted ELO1 which was involved in the elongation of C14 fatty acid (FA) to C16 FA...
March 2018: Microbiological Research
Risheng Ye, Ruth Gordillo, Mengle Shao, Toshiharu Onodera, Zhe Chen, Shiuhwei Chen, Xiaoli Lin, Jeffrey A SoRelle, Xiaohong Li, Miao Tang, Mark P Keller, Regina Kuliawat, Alan D Attie, Rana K Gupta, William L Holland, Bruce Beutler, Joachim Herz, Philipp E Scherer
The compensatory proliferation of insulin-producing β cells is critical to maintaining glucose homeostasis at the early stage of type 2 diabetes. Failure of β cells to proliferate results in hyperglycemia and insulin dependence in patients. To understand the effect of the interplay between β cell compensation and lipid metabolism upon obesity and peripheral insulin resistance, we eliminated LDL receptor-related protein 1 (LRP1), a pleiotropic mediator of cholesterol, insulin, energy metabolism, and other cellular processes, in β cells...
February 19, 2018: Journal of Clinical Investigation
Yue Yao, Qiang Li, Ping Gao, Wei Wang, Lili Chen, Jinchao Zhang, Yi Xu
Abnormal regulation of lipid metabolism is associated with type 2 diabetes mellitus (T2DM). GLP-1 as a new treatment for T2DM, has unique effects in modulating cholesterol homeostasis. However, the mechanism of this effect is largely missing. The aim of this study was to determine the effects of GLP-1 on cholesterol-induced lipotoxicity in hepatocytes and examine the underlying mechanisms. The cell viability was determined, and caspase-3 was used to detect the effects of GLP-1 on cholesterol-induced apoptosis...
February 14, 2018: Biochemical and Biophysical Research Communications
Yuanyuan Zheng, Tiantian Liu, Zhiqiang Wang, Yang Xu, Quanbin Zhang, Dali Luo
Non-alcoholic fatty-liver disease (NAFLD), caused by elevated hepatic lipids, inflammation and oxidative stress, is the most common liver disease globally. Low molecular weight fucoidan (LMWF), a sulfated polysaccharide extracted from brown seaweeds, has shown strong anti-inflammatory and antioxidant activities, which has not been explored in diabetes-induced NAFLD. Therefore, the present study sought to determine whether LMWF protects obese diabetic db/db mice against NAFLD. Results showed LMWF administration decreased plasma level of alanine aminotransferase, aspartate aminotransferase, total cholesterol, and triglyceride, as well as alleviated hepatic accumulation of triglyceride and total cholesterol in db/db mice...
February 12, 2018: International Journal of Biological Macromolecules
Hong Yang, Anyun Feng, Sundong Lin, Lechu Yu, Xiufei Lin, Xiaoqing Yan, Xuemian Lu, Chi Zhang
Our previous studies showed that both exogenous and endogenous FGF21 inhibited cardiac apoptosis at the early stage of type 1 diabetes. Whether FGF21 induces preventive effect on type 2 diabetes-induced cardiomyopathy was investigated in the present study. High-fat-diet/streptozotocin-induced type 2 diabetes was established in both wild-type (WT) and FGF21-knockout (FGF21-KO) mice followed by treating with FGF21 for 4 months. Diabetic cardiomyopathy (DCM) was diagnosed by significant cardiac dysfunction, remodeling, and cardiac lipid accumulation associated with increased apoptosis, inflammation, and oxidative stress, which was aggravated in FGF21-KO mice...
February 14, 2018: Cell Death & Disease
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