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Sifan Chen, Zhongliang Zhao, Liangru Ke, Zilun Li, Wenxue Li, Zili Zhang, Ying Zhou, Xiang Feng, Wei Zhu
Insulin resistance serves as "common soil" for promoting the development of metabolic diseases; however, the precise pathological factors leading to insulin resistance are not well clarified. Resveratrol (Res) is a natural polyphenolic compound with anti-inflammatory and antioxidative effects. However, effects and mechanisms of Res on glucose metabolism in adipocytes remain largely unknown. In this study, we show Res treatment significantly increases glucose uptake in insulin-resistant 3T3-L1 adipocytes in vitro...
February 13, 2018: Journal of Nutritional Biochemistry
Fushen Yang
PURPOSE: To investigate the expression of sirtuin type 1 (Sirt1) and adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) in non-small cell lung cancer (NSCLC), and to explore the mechanism of their functions in NSCLC. METHODS: Cancer tissues (NSCLC group) and the adjacent normal healthy tissues (control group) of 50 patients with NSCLC were selected, and H&E staining was performed to identify the histopathological differences. Reverse transcription polymerase chain reaction (RT-PCR), immunofluorescence staining and Western blot were performed to detect the expression of Sirt1 and AMPK in tissues of NSCLC group and control group...
January 2018: Journal of B.U.ON.: Official Journal of the Balkan Union of Oncology
Hilal Ahmad Parray, Jameel Lone, Jong Pil Park, Jang Won Choi, Jong Won Yun
OBJECTIVE: The aim of this study was to explore the browning and antioxidative effects of magnolol in 3T3-L1 adipocytes, as recruitment of beige-like adipocytes (browning) by natural compounds is being considered as a promising strategy to fight against obesity. METHODS: Magnolol-induced browning effect was evaluated by determining the expression levels of specific marker genes and proteins using real-time polymerase chain reaction and immunoblotting, respectively...
February 5, 2018: Nutrition
Sara Bianchi, Luca Giovannini
The mTOR pathway plays a crucial role in many human diseases, mostly associated with an over hyperactivity of the mTOR signaling, which makes its inhibitors potentially effective therapeutics. Thus, it is important to consider not only the mTOR pathway, but also all those factors that play a key role in its regulation, such as SIRT1 and AMPK. We previously demonstrated the role of some nutraceutical SIRT1 modulators in AMPK and mTOR pathway, showing the presence of a synergistic effect. Now we take further our research by evaluating the effect of berberine, quercetin, tyrosol, and ferulic acid on the mTOR/S6K1/4E-BP1 signaling, along with the existence of any synergistic effect between the following associations: berberine + tyrosol, tyrosol + ferulic acid, ferulic acid + quercetin...
March 14, 2018: Nutrition and Cancer
Shuyi Wang, Cong Wang, Subat Turdi, Kacy L Richmond, Yingmei Zhang, Jun Ren
BACKGROUND AND AIMS: Uncorrected obesity contributes to cardiac remodeling and contractile dysfunction although the underlying mechanism remains poorly understood. Mitochondrial aldehyde dehydrogenase (ALDH2) is a mitochondrial enzyme with some promises in a number of cardiovascular diseases. This study was designed to evaluate the impact of ALDH2 on cardiac remodeling and contractile property in high fat diet-induced obesity. METHODS: Wild-type (WT) and ALDH2 transgenic mice were fed low (10% calorie from fat) or high (45% calorie from fat) fat diet for 5 months prior to the assessment of cardiac geometry and function using echocardiography, IonOptix system, Lectin, and Masson Trichrome staining...
March 13, 2018: International Journal of Obesity: Journal of the International Association for the Study of Obesity
Jonathan Fusi, Sara Bianchi, Simona Daniele, Silvia Pellegrini, Claudia Martini, Fabio Galetta, Luca Giovannini, Ferdinando Franzoni
Oxidative stress arises from an imbalance between the production of free radicals and antioxidant defences. Several studies have suggested that dietary antioxidants (such as polyphenols and berberine) may counteract oxidative stress through the involvement of the Sirtuin 1/Adenosine Monophosphate-Activated Protein Kinase (SIRT1/AMPK) pathway. The aim of this study was to evaluate the direct and specific antioxidant activity of some natural compounds, as well as their ability to modulate the expression of SIRT1 and the activation of AMPK...
March 8, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Peng Liu, Tingting Feng, Xuan Zuo, Xiao Wang, Jinque Luo, Ni Li, Xiaowan Han, Ningyu Zhu, Suowen Xu, Yanni Xu, Zheng Gen Jin, Shuyi Si
Sirtuin 1 (SIRT1) is an NAD+ -dependent protein deacetylase that plays a critical role in controlling energy metabolism, stress response and aging. Hence, enhancing SIRT1 activity could be a potential therapeutic strategy to treat metabolic diseases such as diabetes. However, pharmacological activators for SIRT1 are scarce to date. In this study, using the optimized high throughput screening, we identified E6155, a piperazine 1, 4- diamide compound, as a new small molecular activator of SIRT1. We further found that E6155 significantly upregulated glucose uptake in cultured mouse liver cells and skeletal muscle cells through increasing SIRT1 deacetylase activity...
March 7, 2018: Biochemical and Biophysical Research Communications
Taewoong Ha, Mi Kyoung Kim, Kwang-Su Park, Woong Jung, Hyunah Choo, Youhoon Chong
(-)-Epigallocatechin-3-gallate (EGCG) is known as a mitochondria-targeted molecule that can prevent mitochondrial deterioration and induce mitochondrial biogenesis by modulating key regulators of mitochondrial metabolism. In this study, we tackled whether derivatization of EGCG could result in enhancement of its effects on mitochondrial biogenesis. EGCG, EGCG peracetate (AcEGCG), and its 4″- O-alkyl substituted congeners prepared by previously reported procedures were biologically evaluated. Interestingly, EGCG and AcEGCG were only marginally effective in inducing mitochondrial biogenesis, while AcEGCG congeners with an alkyl group at the 4″- O position showed significantly increased biological activity compared to their parent compound...
March 8, 2018: Journal of Agricultural and Food Chemistry
Tomasz Szkudelski, Katarzyna Szkudelska
Alcohol abuse is associated with numerous health problems, including metabolic disturbances and liver damage. Therefore, different compounds are continuously being tested to evaluate their potential effectiveness in reducing these harmful changes. Animal studies clearly show that resveratrol is capable of ameliorating some consequences of ethanol ingestion. Resveratrol is a naturally occurring diphenolic compound having pleiotropic, health-promoting properties. Its beneficial action have been also demonstrated in animal models with ethanol-induced metabolic disturbances and liver injury...
March 4, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Guoyuan Qi, Rui Guo, Haoyu Tian, Lixia Li, Hua Liu, Yashi Mi, Xuebo Liu
SCOPE: Circadian clock plays a principal role in orchestrating our daily physiology and metabolism, and their perturbation can evoke metabolic diseases such as fatty liver and insulin resistance. Nobiletin (NOB) has been demonstrated to possess antitumor and neuroprotective activities. The objective of the current study is to determine potential effects of NOB on modulating the core clock gene Bmal1 regarding ameliorating glucolipid metabolic disorders. RESULTS: Our results revealed that NOB partially reverse the relatively shallow daily oscillations of circadian clock genes and reset phase-shifting circadian rhythms in primary hepatocytes under metabolic disorders conditions...
February 28, 2018: Biochimica et Biophysica Acta
Chun-Fang, Bo-Bo Zhang, Lin-Han, Cai-Feng Gao, Min-Wang
d-Fagomine, an analogue of 1-deoxynojirimycin (DNJ), has been shown to have hypoglycemic activity. This study is aimed at investigating if d-fagomine could attenuate high glucose-induced oxidative stress in human umbilical vein endothelial cells (HUVECs) and elucidate the underlying mechanism. Our results showed that d-fagomine reduced intracellular reactive oxygen species (ROS) production and malondialdehyde (MDA) levels. It also reversed the decrease of superoxide dismutases (SOD) and glutathione reductase (GR) activity, suggesting an inhibitory effect of d-fagomine on oxidative damage in HUVECs...
February 28, 2018: Journal of Agricultural and Food Chemistry
Diana Moreira, Jérôme Estaquier, Anabela Cordeiro-da-Silva, Ricardo Silvestre
The study of host AMP-activated protein kinase (AMPK) activation during Leishmania infection imposes distinct types of techniques to measure protein expression and activation, as well as to quantify, at transcription and translational levels, its downstream targets. The investigation of host AMPK protein modulation during Leishmania infection should primarily be assessed during in vitro infections using as a host murine bone marrow-derived macrophages (BMMos). The infection outcome is assessed measuring the percentage of infected cells in the context of BMMos...
2018: Methods in Molecular Biology
Chen Li, Wanqing Sun, Chunhu Gu, Zheng Yang, Nanhu Quan, Jingrun Yang, Zhaoling Shi, Lu Yu, Heng Ma
Clinical observations have demonstrated a link between chronic pain and increased ischemic heart disease mortality, but the mechanisms remain elusive. Reactive aldehydes have recently been confirmed as a new player in pain pathologies, while our previous study demonstrated that reactive aldehydes (4-HNE) induced carbonyl stress contributing to myocardial ischemic intolerance. The aim of this study was to explore whether chronic pain increases susceptibility to myocardial ischemia/reperfusion (MI/R) injury and to investigate the underlying mechanisms focusing on toxic aldehyde and carbonyl stress...
2018: Theranostics
S C Bridgeman, G C Ellison, P E Melton, P Newsholme, Cds Mamotte
There is a growing body of evidence that links epigenetic modifications to type 2 diabetes. Researchers have more recently investigated effects of commonly used medications, including those prescribed for diabetes, on epigenetic processes. This work reviews the influence of the widely used antidiabetic drug metformin on epigenomics, microRNA levels and subsequent gene expression and potential clinical implications. Metformin may influence the activity of numerous epigenetic modifying enzymes, mostly via modulating the activation of AMP-activated protein kinase (AMPK)...
February 19, 2018: Diabetes, Obesity & Metabolism
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
Ching-Hou Ma, Yen Chun Chiua, Chin-Hsien Wu, I-Ming Jou, Yuan-Kun Tu, Ching-Hsia Hung, Pei-Ling Hsieh, Kun-Ling Tsai
Emerging evidence has indicated that the perturbed expression of homocysteine (Hcy) may induce mitochondrial dysfunction and disturb bone metabolism. Sirtuin 1 (SIRT1) and AMP-activated protein kinase (AMPK) are two critical sensors that regulate mitochondrial biogenesis and have been recognized as therapeutic targets in osteoarthritis (OA). This study was designed to test whether Hcy caused pro-osteoarthritic changes through modulation of SIRT1 and AMPK. Our results showed that administration of Hcy reduced the SIRT1/AMPK/PGC-1α signaling in chondrocytes, leading to mitochondrial dysfunction as a result of increased oxidative stress and apoptosis...
January 31, 2018: Redox Biology
Lin Wang, Nanhu Quan, Wanqing Sun, Xu Chen, Courtney Cates, Thomas Rousselle, Xinchun Zhou, Xuezhong Zhao, Ji Li
Aim: A longevity gene, Sirtuin 1 (SIRT1) and energy sensor AMP-activated protein kinase (AMPK) have common activators such as caloric restriction, oxidative stress and exercise. The objective of this study is to characterize the role of cardiomyocyte SIRT1 in age-related impaired ischemic AMPK activation and increased susceptibility to ischemic insults. Methods and Results: Mice were subjected to ligation of left anterior descending coronary artery for in vivo ischemic models...
February 2, 2018: Cardiovascular Research
Eun Nim Kim, Min Young Kim, Ji Hee Lim, Yaeni Kim, Seok Joon Shin, Cheol Whee Park, Yong-Soo Kim, Yoon Sik Chang, Hye Eun Yoon, Bum Soon Choi
BACKGROUND AND AIMS: This study evaluated the effects of resveratrol on arterial aging and the renin-angiotensin system (RAS) in mice and vascular smooth muscle cells (VSMCs). METHODS: Aging mice were divided into control and resveratrol groups. Histological changes, inflammation, oxidative stress, RAS components, and the expression of AMP-activated protein kinase (AMPK), silent information regulator T1 (SIRT1), peroxisome proliferator-activated receptor-γ co-activator 1α (PGC-1α), and anti-oxidative enzymes was measured in thoracic aortas of 24-month-old mice...
February 2, 2018: Atherosclerosis
Xinyi Gu, Zhengxu Cai, Ming Cai, Kun Liu, Dan Liu, Qinsong Zhang, Jing Tan, Qiang Ma
Resveratrol has also been approved for use in enhancing plant disease resistance and reducing pesticide use. A number of studies have shown that the disease resistance of crops treated with resveratrol is markedly improved. The aim of the present study was to examine the protective effect of resveratrol against alcohol‑induced neurodegeneration occurred and its association with AMP‑activated protein kinase (AMPK)/sirtuin 1 (SIRT1)/p38 in rats and humans. ELISA, caspase‑3 activity and western blot analyses were employed in the present study...
January 25, 2018: Molecular Medicine Reports
Ya-Nan Song, Ding Yuan, Chang-Cheng Zhang, Luo-Pei Wang, Yu-Min He, Ting Wang, Zhi-Yong Zhou
To investigate the effects of saponins extracted from Panax japonicus(SPJ) on cardiomyocyte apoptosis in natural aging rats and explore its underlying mechanisms. SD male rats were randomly divided into four groups: young control group, natural aging group, SPJ low dose group and SPJ high dose group, with 10 rats in each group. The rats in natural aging group, SPJ low and high dose groups were respectively treated with normal saline, SPJ 10 and 60 mg•kg-1•d-1 from the beginning of 18 month-old, 6 days per week for 6 months till 24 month-old...
December 2017: Zhongguo Zhong Yao za Zhi, Zhongguo Zhongyao Zazhi, China Journal of Chinese Materia Medica
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