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obesity-induced sperm DNA methylation changes at satellite repeats are reprogrammed in rat offspring

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Asian Journal of Andrology 2016年第6期18卷 930-936页

作者： Neil A Youngson Virginie Lecomte Christopher A Maloney Preston Leung Jia Liu Luke B Hesson Fabio Luciani Lutz Krause Margaret J Morris Department of Pharmacology School of Medical Sciences UNSW Australia Sydney NSW 2052 Australia Inflammation and Infection Research School of Medical Sciences UNSW Australia Sydney NSW 2052 Australia Adult Cancer Program Lowy Cancer Research Centre and Prince of Wales Clinical School UNSW Australia Sydney NSW 2052 Australia QIMR Berghofer Medical Research Institute Herston Brisbane Queensland 4006 Australia University of Queensland Diamantina Institute Translational Research Institute University of Queensland 37 Kent Street Woolleongabba Queensland 4102 Australia

There is now strong evidence that the paternal contribution to offspring phenotype at fertilisation is more than just DNA. However, the identity and mechanisms of this nongenetic inheritance are poorly understood. One of the more important questions in this research area is： do changes in sperm DNA methylation have phenotypic consequences for offspring？ We have previously reported that offspring of obese male rats have altered glucose metabolism compared with controls and that this effect was inherited through nongenetic means. Here, we describe investigations into sperm DNA methylation in a new cohort using the same protocol. Male rats on a high-fat diet were 30% heavier than control-fed males at the time of mating （16-19 weeks old, n = 14/14）. A small （0.25%） increase in total 5-methyl-2＇-deoxycytidine was detected in obese rat spermatozoa by liquid chromatography tandem mass spectrometry. Examination of the repetitive fraction of the genome with methyI-CpG binding domain protein-enriched genome sequencing （MBD-Seq） and pyrosequencing revealed that retrotransposon DNA methylation states in spermatozoa were not affected by obesity, but methylation at satellite repeats throughout the genome was increased. However, examination of muscle, liver, and spermatozoa from male 27-week-old offspring from obese and control fathers （both groups from n = 8 fathers） revealed that normal DNA methylation levels were restored during offspring development. Furthermore, no changes were found in three genomic imprints in obese rat spermatozoa. Our findings have implications for transgenerational epigenetic reprogramming. They suggest that postfertilization mechanisms exist for normalising some environmentally-induced DNA methylation changes in sperm cells.

关键词： methylation obesity spermatozoa

obesity, metabolic abnormalities, and mortality in older men

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Journal of Geriatric Cardiology 2018年第6期15卷 422-427页

作者： Rong ZHANG Sheng-Yong DONG Wei-Min WANG Shu-Yang FEI Hang XIANG Qiang ZENG Health Management Institute Chinese PLA General Hospital Beijing China Department of Cardiology Chinese Navy General Hospital Beijing China Healtheare Department Agency for Offices Administration of PLA Beijing China Department of Clinical Medicine School of Preclinical Medicine Capital University of Medical Sciences Beijing China

Background Older adults are prone to obesity and metabolic abnormalities and recommended to pursue a normal weight especially when obesity and metabolic abnormalities are co-existed. However, few studies have reported the possible differences in the effect of obesity on outcomes between older adults with metabolic abnormalities and those without metabolic abnormalities. Methods A total of 3485 older men were included from 2000 to 2014. All-cause mortality and cardiovascular mortality were obtained during a mean follow-up of five years Metabolic abnormalities were defined as having established hypertension, diabetes, or dyslipidemia and taking the disease-related medications. All participants were stratified by the presence or absence of metabolic abnormalities. Results In the non-metabolic abnormalities group, all-cause and cardiovascular deaths were lowest in overweight participants and highest in obese participants. In the metabolic abnormalities group, mortality was also lowest in overweight participants but highest in participants with normal weight. After adjustment for covariates, hazard ratios （95% CI） for all-cause death and cardiovascular death were 0.68 （0.51, 0.92） and 0.59 （0.37, 0.93）, respectively, in overweight participants with metabolic abnormalities. Furthermore, obesity was not associated with mortality risk in both groups. These findings were unchanged in stratified analyses. Conclusions Overweight was negatively associated with mortality risk in older men with metabolic abnormalities but not in those without metabolic abnormalities. obesity did not increase death risk regardless of metabolic abnormalities. These findings suggest that the recommendation of pursuing a normal weight may be wrong in overweight/obese older men, especially for those with metabolic abnormalities.

关键词： obesity Older men Metabolic abnormality Mortality

obesity is positively Associated with Depression in Older Adults:Role of Systemic Inflammation

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Biomedical and Environmental Sciences 2023年第6期36卷 481-489页

作者： GUO Ye Xin WANG An Qi GAO Xin NA Jun ZHE Wei ZENG Yi ZHANG Jing Rui JIANG Yuan Jing YAN Fei YUNUS Mukaram WANG Hui YIN Zhao Xue Division of Non-communicable Diseases and Elderly Health Management Chinese Center for Disease Control and PreventionBeijing 102206China Liaoning Provincial Center for Diseases Control and Prevention Shenyang 110000LiaoningChina Xinjiang Uygur Autonomous Region Centre for Disease Control and Prevention Urumqi 830002XinjiangChina Center for the Study of Aging and Human Development and the Geriatric Division of School of Medicine Duke UniversityDurham 27701NCUSA Center for Healthy Aging and Development Studies National School of DevelopmentPeking UniversityBeijing 100871China Yuanbao Center for Diseases Control and Prevention Dandong 118000LiaoningChina Korla Center for Diseases Control and Prevention Korla 841000XinjiangChina Liudaokou Community Health Service Centre Dandong 118000LiaoningChina

Objective We aimed to explore the association between obesity and depression and the role of systemic inflammation in older *** Adults≥65 years old(n=1,973)were interviewed at baseline in 2018 and 1,459 were followed up in *** and abdominal obesity were assessed,and serum C-reactive protein(CRP)levels were measured at *** status was assessed at baseline and at *** regression was used to analyze the relationship between obesity and the incidence of depression and worsening of depressive symptoms,as well as the relationship between obesity and CRP *** associations of CRP levels with the geriatric depression scale,as well as with its three dimensions,were investigated using multiple linear *** General obesity was associated with worsening depression symptoms and incident depression,with an odds ratio(OR)[95%confidence interval(CI)]of 1.53(1.13-2.12)and 1.80(1.23-2.63),especially among old male subjects,with OR(95%CI)of 2.12(1.25-3.58)and 2.24(1.22-4.11),respectively;however,no significant relationship was observed between abdominal obesity and *** addition,general obesity was associated with high levels of CRP,with OR(95%CI)of 2.58(1.75-3.81),especially in subjects free of depression at baseline,with OR(95%CI)of 3.15(1.97-5.04),and CRP levels were positively correlated with a score of specific dimension(life satisfaction)of depression,Pobesity,rather than abdominal obesity,was associated with worsening depressive symptoms and incident depression,which can be partly explained by the systemic inflammatory response,and the impact of obesity on depression should be taken more seriously in the older male population.

关键词： Depression obesity Older adults Body mass index Inflammatory reaction

obesity rather than Metabolic Syndrome is a Risk Factor for Subclinical Hypothyroidism and Thyroid Autoimmunity

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Biomedical and Environmental Sciences 2021年第10期34卷 819-823页

作者： YAO Jin Yin LIU Peng ZHANG Wei WANG Ke Wei LYU Chun Peng ZHANG Zhi Wei CHEN Xiang Lan CHEN Yi WANG Xue Song DING Yong Xia MA Li Jun WANG Jing SUN Dian Jun Center for Endemic Disease Control Chinese Center for Disease Control and PreventionHarbin Medical UniversityHarbin 150081HeilongjiangChina Institute of Endemic Disease Control Shandong ProvinceJinan 250000ShandongChina Heze Center for Disease Control and Prevention Heze 274000ShandongChina Jining Center for Disease Control and Prevention Jining 272000ShandongChina

In recent years,the incidences of thyroid diseases have gradually increased,and they may be associated with the development of diagnostic technologies,elevated public health awareness,nuclear radiation,environmental pollution,changes in lifestyle,work stress,excessive iodine intake,and other *** obesity can cause changes to the hypothalamic-pituitary-thyroid axis and deiodinase[1],obesity may be closely related to the high rate of thyroid diseases.

关键词： immunity obesity elevated

obesity leads to higher risk of sperm DNA damage in infertile patients

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Asian Journal of Andrology 2013年第5期15卷 622-625页

作者： Charlotte Dupont Celine Fauret Nathalie Sermondade Marouane Boubaya Florence Eustache Patrice Clement Pascal Briot Isabelle Berthaut Vincent Levy Isabelle Cedrin-Durnerin Brigitte Benzacken Pascale Chavatte-Palmer Rachel Levy AP-H P Jean Verdier hospital Reproductive Biology unit-CECOS F-93140 Bondy France paris 13 University Sorbonne Paris Cite Nutritional epidemiology unit (UREN U M R U557 Inserm Ul125 Inra Cnam CRNH IdF) F-93017 Bobigny France INRA UMR1198 Biologie du Developpement et Reproduction (Biology of Reproductive and development unit) F-78352 Jouy en Josas France ENVA veterinary school F-94704 Maisons-Alfort France AP-HP Avicenne hospital Clinical research unit F-93000 Bobigny France Clement laboratory Laboratoire Clement F-93150 Le Blanc Mesnil France American hospital of Paris Reproductive Biology unit F-92200 Neuilly sur seine France AP-HP Tenon hospital Reproductive Biology unit-CECOS F-75020 Paris France AP-HP Jean Verdier hospital Reproductive medicine unit Paris 13 University F-93140 Bondv. France

There has been a growing interest over the past few years in the impact of male nutrition on fertility. Infertility has been linked to male overweight or obesity, and conventional semen parameter values seem to be altered in case of high body mass index （BMI）. A few studies assessing the impact of BMI on sperm DNA integrity have been published, but they did not lead to a strong consensus. Our objective was to explore further the relationship between sperm DNA integrity and BMI, through a 3-year multicentre study. Three hundred and thirty male partners in subfertile couples were included. Using the terminal uridine nick-end labelling （TUNEL） assay, we observed an increased rate of sDerm DNA damage in obese men （odds ratio （95% confidence interval）： 2.5 （1.2-5.1））.

关键词： male infertility obesity overweight sperm sperm DNA fragmentation

Long-term exposure to titanium dioxide nanoparticles promotes diet-induced obesity through exacerbating intestinal mucus layer damage and microbiota dysbiosis

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Nano Research 2021年第5期14卷 1512-1522页

作者： Xiaoqiang Zhu Lijun Zhao Zhi Liu Qibing Zhou Yanhong Zhu Yuliang Zhao Xiangliang Yang National Engineering Research Center for Nanomedicine College of Life Science and TechnologyHuazhong University of Science and TechnologyWuhan430074China Department of Biotechnology College of Life Science and TechnologyHuazhong University of Science and TechnologyWuhan430074China CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety National Center for Nanoscience and Technology of ChinaBeijing100190China

Titanium dioxide nanoparticles (TiO2-NPs) are commonly used as food additives, including some high-fat foods that are risk factors for obesity. However, little is known about the effects of chronic TiO2-NPs digestion in the population on high fat diet (HFD). Herein, we reported that TiO2-NPs exacerbated HFD-induced obesity by disruption of mucus layer and alterations of gut microbiota. Oral intake of TiO2-NPs significantly increased body weight, liver weight, and amount of adipose tissues, especially in HFD-fed mice. Mechanistic studies revealed TiO2-NPs induced colonic mucus layer disruption and obesity-related microbiota dysbiosis. The damage on mucus was demonstrated through down-regulation of Muc2 gene and the absorption of mucin protein by TiO2-NPs. Consequently, mucus layer damage combined microbiota dysbiosis escalated the low-grade systemic inflammation, which exacerbated HFD-induced obesity. In contrast, gut microbiota depletion eliminated these effects, indicating gut microbiota were necessary for TiO2-NPs-induced inflammation and obesity. All the results stated the alarming role of TiO2-NPs in the HFD-driven obesity and emphasized the reevaluating the health impacts of nanoparticles commonly used in daily life, particularly, in susceptible population.

关键词： titanium dioxide nanoparticles nanosafety obesity mucus layer gut microbiota

obesity, fatty liver disease and intestinal microbiota

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World Journal of Gastroenterology 2014年第44期20卷 16452-16463页

作者： Nur Arslan Department of Pediatrics Division of Pediatric Gastroenterology Nutrition and Metabolism Dokuz Eylul University Faculty of Medicine Department of Molecular Medicine Dokuz Eylul University Faculty of Medicine

Nonalcoholic fatty liver disease(NAFLD) is a chronic liver disorder that is increasing in prevalence with the worldwide epidemic of obesity. NAFLD is the hepatic manifestation of the metabolic syndrome. The term NAFLD describes a spectrum of liver pathology ranges from simple steatosis to steatosis with inflammation nonalcoholic steatohepatitis and even cirrhosis. Metabolic syndrome and NAFLD also predict hepatocellular carcinoma. Many genetic and environmental factors have been suggested to contribute to the development of obesity and NAFLD, but the exact mechanisms are not known. Intestinal ecosystem contains trillions of microorganisms including bacteria, Archaea, yeasts and viruses. Several studies support the relationship between the intestinal microbial changes and obesity and also its complications, including insulin resistance and NAFLD. Given that the gut and liver are connected by the portal venous system, it makes the liver more vulnerable to translocation of bacteria, bacterial products, endotoxins or secreted cytokines. Altered intestinal microbiota(dysbiosis) may stimulate hepatic fat deposition through several mechanisms: regulation of gut permeability, increasing low-grade inflammation, modulation of dietary choline metabolism, regulation of bile acid metabolism and producing endogenous ethanol. Regulation of intestinal microbial ecosystem by diet modifications or by using probiotics and prebiotics as a treatment for obesity and its complications might be the issue of further investigations.

关键词： Intestinal microbiota Dysbiosis Nonalcoholic fatty liver disease obesity

Metformin booster adipocyte-targeted gene therapy for the treatment of obesity and related metabolic syndromes

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Science China Chemistry 2022年第4期65卷 796-809页

作者： Jie Chen Jee Young Chung Huapan Fang Lin Lin Yong-Hee Kim Huayu Tian Xuesi Chen Key Laboratory of Polymer Ecomaterials Changchun Institute of Applied ChemistryChinese Academy of SciencesChangchun 130022China Department of Bioengineering Institute for Bioengineering and Biopharmaceutical ResearchBK 21 Plus Future Biopharmaceutical Human Resources Training and Research TeamHanyang University133-791 SeoulRepublic of Korea

obesity has become an important public problem that endangers human conditions and urgently needs to be solved. However,most weight-loss drugs on the market have little effect and are accompanied by adverse effects such as strokes and heart ***, we construct an adipocyte-targeting polypeptide-based gene carrier consisting of an adipocyte-targeting peptide and ptoluylsulfonyl arginine-modified polylysine(ATS-PLL-RT), which can specifically bind to the prohibitin of mature *** further construct a short hairpin RNA(shRNA) to simultaneously silence fatty acid binding proteins 4 and 5(shFABP4/5).FABPs are molecular chaperones for fatty acid metabolism and storage in cells. Moreover, we introduce metformin for combined therapy. First, the metformin combination can effectively improve the efficiency of gene transfection. In addition, metformin itself has an alleviating effect on diet-induced obesity and relevant metabolic diseases. The combination treatment of obese mice with ATS-PLL-RT/shFABP4/5 and metformin achieves body weight reduction and metabolic recovery. This study provides a potentially effective strategy for the clinical treatment of obesity as well as mitigating obesity-induced metabolic syndromes.

关键词： FABP4/5 gene therapy insulin resistance metformin obesity

obesity promotes oxidative stress and exacerbates blood-brain barrier disruption after high-intensity exercise

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Journal of Sport and Health Science 2017年第2期6卷 225-230页

作者： Hee-Tae Roh Su-Youn Cho Wi-Young So Department of Physical Education Dong-A University Busan 604-714 Republic of Korea School of Taekwondo College of Creative Human ResourcesYoungsan UniversityYangsan-si 626-790Republic of Korea Sports and Health Care Major College of Humanities and ArtsKorea National University of TransportationChungju-si 380-702Republic of Korea

Purpose: The purpose of this study was to investigate the effects of obesity and high-intensity acute exercise on oxidant-antioxidant status,neurotrophic factor expression, and blood-brain barrier(BBB) ***: Twenty-four healthy, untrained men(12 non-obese(mean 14.9% body fat) and 12 obese subjects(mean 29.8% body fat)) performed20 min of continuous submaximal aerobic exercise at 85% maximal oxygen consumption. Blood sampling was performed to examine the oxidant-antioxidant status(reactive oxygen species(ROS) and superoxide dismutase(SOD)), neurotrophic factors(brain-derived neurotrophic factor(BDNF) and nerve growth factor(NGF)), and BBB disruption(S100β and neuron-specific enolase) before and after acute ***: The obese group showed significantly higher pre-exercise serum ROS levels and significantly lower pre-exercise serum SOD levels than the non-obese group(p < 0.05). Serum ROS, SOD, BDNF, NGF, and S100β levels were significantly increased post-exercise compared with pre-exercise levels in both the non-obese and the obese groups(p < 0.05). The obese group showed significantly higher serum ROS, BDNF, NGF,and S100β levels post-exercise compared to the non-obese group(p < 0.05).Conclusion: Our study suggests that episodic vigorous exercise can increase oxidative stress and blood neurotrophic factor levels and induce disruption of the BBB. Moreover, high levels of neurotrophic factor in the blood after exercise in the obese group may be due to BBB disruption,and it is assumed that oxidative stress was the main cause of this BBB disruption.

关键词： Antioxidant enzyme Blood-brain barrier Exercise Neurotrophic factor obesity Oxidative stress