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Kwang-Youn Kim, Hyun-Jun Jang, Yong Ryul Yang, Kwang-Il Park, JeongKon Seo, Il-Woo Shin, Tae-Il Jeon, Soon-Cheol Ahn, Pann-Ghill Suh, Timothy F Osborne, Young-Kyo Seo
Dysregulated autophagy is associated with steatosis and non-alcoholic fatty liver disease (NAFLD), however the mechanisms connecting them remain poorly understand. Here, we show that co-administration of lovastatin and ezetimibe (L/E) significantly reverses hepatic triglyceride accumulation concomitant with an increase in SREBP-2 driven autophagy in mice fed a high-fat diet (HFD). We further show that the statin mediated increase in SREBP-2 directly activates expression of patatin-like phospholipase domain-containing enzyme 8 (PNPLA8) gene, and PNPLA8 associates with autophagosomes and is associated with a decrease in cellular triglyceride...
October 21, 2016: Scientific Reports
Sunil Sirohi, Arriel Van Cleef, Jon F Davis
Binge eating and binge alcohol intake are behavioral manifestations of pathological feeding and alcohol use disorder (AUD), respectively. Binge-feeding and AUD have high comorbidity with other psychiatric disorders such as depression, which could have important implications for the management of these conditions. Importantly, these behaviors share many common features suggesting a singular etiology. However, the nature by which binge-feeding affects the development or maintenance of AUD is unclear. The present study examined the impact of a binge-feeding from a nutritionally complete high-fat diet (HFD) on initiation and maintenance of alcohol intake, anxiolytic behavior and central genetic changes in brain regions that control alcohol-reinforced behaviors...
October 17, 2016: Physiology & Behavior
Zi Lin, Zheng-Feng Wu, Cui-Hua Jiang, Qing-Wen Zhang, Sheng Ouyang, Chun-Tao Che, Jian Zhang, Zhi-Qi Yin
BACKGROUND: Hepatic steatosis (HS) is the early stage of nonalcoholic fatty liver disease which is caused by impaired hepatic lipid homeostasis. Cyclocarya paliurus, an herbal tea consumed in China, has been demonstrated to ameliorate abnormal lipid metabolism for the treatment of metabolic diseases. PURPOSE: We aimed to investigate the regulative effect of chloroform extract from Cyclocarya paliurus (ChE) on treatment of HS, as well as key factors involved in hepatic lipid metabolism...
November 15, 2016: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
Andrew J Teichtahl, Donna M Urquhart, Yuanyuan Wang, Anita E Wluka, Richard O'Sullivan, Graeme Jones, Flavia M Cicuttini
BACKGROUND: Degenerative disc disease of the lumbar spine is common, with severe disease increasing the risk for chronic low back pain. This cross-sectional study examined whether disc degeneration is representative of a 'whole-organ' pathology, by examining its association with bone (vertebral endplate) and soft tissue (paraspinal muscle fat) abnormalities. METHODS: Seventy-two community-based individuals unselected for low back pain, had Magnetic Resonance Imaging (MRI)...
October 21, 2016: BMC Musculoskeletal Disorders
Janine Donaldson, Michael Taurai Madziva, Kennedy Honey Erlwanger
Objective: The current study aimed to investigate the impact of high-fat diets composed of different animal and vegetable fat sources on serum metabolic health markers in Japanese quail, as well as the overall lipid content and fatty acid profiles of the edible bird tissues following significantly increased dietary lipid supplementation. Methods: Fifty seven male quail were divided into six groups and fed either a standard diet or a diet enriched with one of five different fats (22 % coconut oil, lard, palm oil, soybean oil or sunflower oil) for 12 weeks...
October 20, 2016: Asian-Australasian Journal of Animal Sciences
Daniel Zysset, Benjamin Weber, Silvia Rihs, Jennifer Brasseit, Stefan Freigang, Carsten Riether, Yara Banz, Adelheid Cerwenka, Cedric Simillion, Pedro Marques-Vidal, Adrian F Ochsenbein, Leslie Saurer, Christoph Mueller
Triggering receptor expressed on myeloid cells-1 (TREM-1) is a potent amplifier of pro-inflammatory innate immune responses, but its significance in non-infectious diseases remains unclear. Here, we demonstrate that TREM-1 promotes cardiovascular disease by exacerbating atherosclerosis. TREM-1 is expressed in advanced human atheromas and is highly upregulated under dyslipidemic conditions on circulating and on lesion-infiltrating myeloid cells in the Apoe(-/-) mouse model. TREM-1 strongly contributes to high-fat, high-cholesterol diet (HFCD)-induced monocytosis and synergizes with HFCD serum-derived factors to promote pro-inflammatory cytokine responses and foam cell formation of human monocyte/macrophages...
October 20, 2016: Nature Communications
FangFang, Hongyan Li, Tingting Qin, Min Li, Shiping Ma
The impaired insulin signaling has been recognized as a common pathogenetic mechanism between diabetes and Alzheimer's disease (AD). In the progression of AD, brain is characterized by defective insulin receptor substrate-1 (IRS-1) and increased oxidative stress. Thymol, a monoterpene phenol isolated from medicinal herbs, has exhibited robust neuroprotective effects. The present study was designed to investigate the protective effect of thymol on HFD-induced cognitive deficits, and explore the possible mechanisms...
October 20, 2016: Metabolic Brain Disease
Yong Xie, Yi Zhang, Zebin Guo, Hongliang Zeng, Baodong Zheng
This study aimed to investigate the effects of total alkaloids from Nelumbinis Plumula (NPA) on insulin resistance (IR) of high-fat diet- (HFD-) induced nonalcoholic fatty liver disease (NAFLD). Rats were fed with HFD for 8 weeks to induce NAFLD. Then, the effect of NPA on ameliorating IR in HFD-induced NAFLD was evaluated. Fasting serum insulin was determined using an enzyme-linked immunosorbent assay (ELISA) kit for insulin following the manufacturer's protocol. Some inflammatory cytokines such as tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6) were determined using ELISA kits to assess the inflammatory burden in rats...
2016: Journal of Diabetes Research
Suganya Venkateshan, Vetriselvan Subramaniyan, Velmurugan Chinnasamy, Sarath Chandiran
OBJECTIVE: Dietary changes play major risk roles in oxidative stress and cardiovascular disease and modulate normal metabolic function. The present study was designed to investigate the ameliorative potential of different extracts of Hemidesmus indicus to experimental high-fat diet in wistar rats, and their possible mechanism of action. MATERIALS AND METHODS: Male wistar rats were divided into 6 groups (n=6/group) and fed with a standard diet (control), high-fat diet (HFD), high-fat diet supplemented with different extracts and positive control for 9 weeks...
September 2016: Avicenna Journal of Phytomedicine
Michiyo Deushi, Mizuko Osaka, Kaku Nakano, Kyoichi Osada, Kensuke Egashira, Masayuki Yoshida
Oxidized cholesterol (oxysterols) plays an important and multifaceted role in lipid metabolism. Here we examined whether dietary oxysterols accelerate hepatic lipid accumulation and inflammation in nonhuman primates. We also examined the effect of the Niemann-Pick C1-like1 inhibitor, ezetimibe (Ez). Macaca fascicularis (5-year-old males) were fed either regular cholesterol + high-fat diet (control-HFD) or oxysterols + high-fat diet (ox-HFD; with 0.015% of oxysterols cholesterol) for 24 weeks. Compared with control-HFD, ox-HFD did not affect plasma lipid levels, but it did affect hepatic lipid levels [total cholesterol, 40...
October 2016: FEBS Open Bio
Sibghatullah Muhammad Ali Sangi
BACKGROUND: Since long high fat diet (HFD) is being blamed for causing fatty degeneration of liver and formation of atheromatous plaques. At present, no proper pharmacotherapy is available for both the conditions. In this study, different substances containing monounsaturated fatty acids were used to observe their protective effects in the HFD induced damage to liver and coronary vessels. OBJECTIVES: To discover effective therapeutic agents for HFD induced fatty degeneration of liver and atheromatous plaques...
July 2016: Pharmacognosy Magazine
X H Sun, M S Yin, Y L Mu
Objective: To investigate the alterations of mTOR signaling pathway and autophagy in the development of type 2 diabetes and early diabetic cardiomyopathy and to study their roles in pathogenesis of diabetic myocardium. Methods: A type 2 diabetes rat model was established by injection of streptozocin after five-week of high fat diet. The rats were randomly divided into control group, experiment group of 2 weeks and experiment group of 4 weeks. Alterations of mTOR, p-mTOR, S6K1, Beclin-1 and LC3-Ⅱ expression in myocardium were determined by Western blot and immunohistochemistry...
October 8, 2016: Zhonghua Bing Li Xue za Zhi Chinese Journal of Pathology
Aurore Woller, Hélène Duez, Bart Staels, Marc Lefranc
To maintain energy homeostasis despite variable energy supply and consumption along the diurnal cycle, the liver relies on a circadian clock synchronized to food timing. Perturbed feeding and fasting cycles have been associated with clock disruption and metabolic diseases; however, the mechanisms are unclear. To address this question, we have constructed a mathematical model of the mammalian circadian clock, incorporating the metabolic sensors SIRT1 and AMPK. The clock response to various temporal patterns of AMPK activation was simulated numerically, mimicking the effects of a normal diet, fasting, and a high-fat diet...
October 18, 2016: Cell Reports
Max C Petersen, Anila K Madiraju, Brandon M Gassaway, Michael Marcel, Ali R Nasiri, Gina Butrico, Melissa J Marcucci, Dongyan Zhang, Abudukadier Abulizi, Xian-Man Zhang, William Philbrick, Stevan R Hubbard, Michael J Jurczak, Varman T Samuel, Jesse Rinehart, Gerald I Shulman
Nonalcoholic fatty liver disease (NAFLD) is a risk factor for type 2 diabetes (T2D), but whether NAFLD plays a causal role in the pathogenesis of T2D is uncertain. One proposed mechanism linking NAFLD to hepatic insulin resistance involves diacylglycerol-mediated (DAG-mediated) activation of protein kinase C-ε (PKCε) and the consequent inhibition of insulin receptor (INSR) kinase activity. However, the molecular mechanism underlying PKCε inhibition of INSR kinase activity is unknown. Here, we used mass spectrometry to identify the phosphorylation site Thr1160 as a PKCε substrate in the functionally critical INSR kinase activation loop...
October 17, 2016: Journal of Clinical Investigation
Letícia Pereira de Brito Sampaio
The ketogenic diet (KD), a high-fat, low-carbohydrate, and adequate-protein diet is an established, effective nonpharmacologic treatment option for intractable childhood epilepsy. The KD was developed in 1921 and even though it has been increasingly used worldwide in the past decade, many neurologists are not familiar with this therapeutic approach. In the past few years, alternative and more flexible KD variants have been developed to make the treatment easier and more palatable while reducing side effects and making it available to larger group of refractory epilepsy patients...
October 2016: Arquivos de Neuro-psiquiatria
Vamsee D Myneni, Aisha Mousa, Mari T Kaartinen
F13A1 gene, which encodes for Factor XIII-A blood clotting factor and a transglutaminase enzyme, was recently identified as a potential causative gene for obesity in humans. In our previous in vitro work, we showed that FXIII-A regulates preadipocyte differentiation and modulates insulin signaling via promoting plasma fibronectin assembly into the extracellular matrix. To understand the role of FXIII-A in whole body energy metabolism, here we have characterized the metabolic phenotype of F13a1-/- mice. F13a1-/- and F13a1+/+ type mice were fed chow or obesogenic, high fat diet for 20 weeks...
October 19, 2016: Scientific Reports
H-L Che, M S Kanthimathi, R Loganathan, K H Yuen, A T B Tan, K R Selvaduray, K Nesaretnam, K-T Teng
BACKGROUND/OBJECTIVES: Evidence shows that tocotrienols potentially reverse various chronic disease progressions caused by the metabolic syndrome. We aimed to investigate the acute effects of a single-dose supplementation of gamma and delta tocotrienols (γδ-T3, 1:4 ratio) compared with those in placebo on the insulinemic, anti-inflammatory and anti-thrombogenic responses in metabolic syndrome subjects. SUBJECTS/METHODS: Thirty metabolic syndrome subjects (15 men and 15 women) were recruited to a randomized, double-blinded and crossover study...
October 19, 2016: European Journal of Clinical Nutrition
G Kerckhofs, M Durand, R Vangoitsenhoven, C Marin, B Van der Schueren, G Carmeliet, F P Luyten, L Geris, K Vandamme
High resolution microfocus X-ray computed tomography (HR-microCT) was employed to characterize the structural alterations of the cortical and trabecular bone in a mouse model of obesity-driven type 2 diabetes (T2DM). C57Bl/6J mice were randomly assigned for 14 weeks to either a control diet-fed (CTRL) or a high fat diet (HFD)-fed group developing obesity, hyperglycaemia and insulin resistance. The HFD group showed an increased trabecular thickness and a decreased trabecular number compared to CTRL animals. Midshaft tibia intracortical porosity was assessed at two spatial image resolutions...
October 19, 2016: Scientific Reports
Gang Chen, Dongsheng Yu, Xue Nian, Junyi Liu, Ronald J Koenig, Bin Xu, Liang Sheng
Nonalcoholic fatty liver disease (NAFLD), the most common form of chronic liver disease, manifests as an over-accumulation of hepatic fat. We have recently shown that mice with genetic knockout of a long non-coding RNA (lncRNA) steroid receptor RNA activator (SRA) (SRAKO) are resistant to high fat diet-induced obesity with a phenotype that includes improved glucose tolerance and attenuated hepatic steatosis. The underlying mechanism was investigated in the present study. We found that hepatic levels of SRA and adipose triglyceride lipase (ATGL), a major hepatic triacylglycerol (TAG) hydrolase, were inversely regulated by fasting in mice, and the expression of liver ATGL was induced by SRAKO under normal and high fat diet (HFD) feeding...
October 19, 2016: Scientific Reports
Tsuyoshi Chiba, Keiko Noji, Shohei Shinozaki, Sachina Suzuki, Keizo Umegaki, Kentaro Shimokado
OBJECTIVES: Non-alcoholic fatty liver disease (NAFLD) is associated with impaired liver function, and resveratrol could suppress NAFLD progression. This study examined the effects of NAFLD on the expression of major cytochrome P450 (CYP) subtypes in the liver and whether the expression could be attenuated by resveratrol. METHODS: C57BL/6 mice (male, 10 weeks of age) were fed a high-fat and high-sucrose (HFHS) diet to induce NAFLD. Major Cyp subtype mRNA expression in the liver was measured by real-time RT-PCR...
October 19, 2016: Journal of Pharmacy and Pharmacology
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