The gut microbiota is emerging as a new factor in the development of obesity. Many studies have described changes in microbiota composition in response to obesity and high fat diet (HFD) at the ...phylum level. In this study we used 16s RNA high throughput sequencing on faecal samples from rats chronically fed HFD or control chow (n = 10 per group, 16 weeks) to investigate changes in gut microbiota composition at the species level. 53.17% dissimilarity between groups was observed at the species level. Lactobacillus intestinalis dominated the microbiota in rats under the chow diet. However this species was considerably less abundant in rats fed HFD (P<0.0001), this being compensated by an increase in abundance of propionate/acetate producing species. To further understand the influence of these species on the development of the obese phenotype, we correlated their abundance with metabolic parameters associated with obesity. Of the taxa contributing the most to dissimilarity between groups, 10 presented significant correlations with at least one of the tested parameters, three of them correlated positively with all metabolic parameters: Phascolarctobacterium, Proteus mirabilis and Veillonellaceae, all propionate/acetate producers. Lactobacillus intestinalis was the only species whose abundance was negatively correlated with change in body weight and fat mass. This species decreased drastically in response to HFD, favouring propionate/acetate producing bacterial species whose abundance was strongly correlated with adiposity and deterioration of metabolic factors. Our observations suggest that these species may play a key role in the development of obesity in response to a HFD.
There is widespread concern that Russia and other countries have launched social-media campaigns designed to increase political divisions in the United States. Though a growing number of studies ...analyze the strategy of such campaigns, it is not yet known how these efforts shaped the political attitudes and behaviors of Americans. We study this question using longitudinal data that describe the attitudes and online behaviors of 1,239 Republican and Democratic Twitter users from late 2017 merged with nonpublic data about the Russian Internet Research Agency (IRA) from Twitter. Using Bayesian regression tree models, we find no evidence that interaction with IRA accounts substantially impacted 6 distinctive measures of political attitudes and behaviors over a 1-mo period. We also find that interaction with IRA accounts were most common among respondents with strong ideological homophily within their Twitter network, high interest in politics, and high frequency of Twitter usage. Together, these findings suggest that Russian trolls might have failed to sow discord because they mostly interacted with those who were already highly polarized. We conclude by discussing several important limitations of our study—especially our inability to determine whether IRA accounts influenced the 2016 presidential election—as well as its implications for future research on social media influence campaigns, political polarization, and computational social science.
We previously showed that paternal high‐fat diet (HFD) consumption programs β‐cell dysfunction in female rat offspring, together with transcriptome alterations in islets. Here we investigated the ...retroperitoneal white adipose tissue (RpWAT) transcriptome using gene and pathway enrichment and pathway analysis to determine whether commonly affected network topologies exist between these two metabolically related tissues. In RpWAT, 5108 genes were differentially expressed due to a paternal HFD; the top 5 significantly enriched networks identified by pathway analysis in offspring of HFD fathers compared with those of fathers fed control diet were: mitochondrial and cellular response to stress, telomerase signaling, cell death and survival, cell cycle, cellular growth and proliferation, and cancer. A total of 187 adipose olfactory receptor genes were down‐regulated. Interrogation against the islet transcriptome identified specific gene networks and pathways, including olfactory receptor genes that were similarly affected in both tissues (411 common genes, P<0.05). In particular, we highlight a common molecular network, cell cycle and cancer, with the same hub gene, Myc, suggesting early onset developmental changes that persist, shared responses to programmed systemic factors, or crosstalk between tissues. Thus, paternal HFD consumption triggers unique gene signatures, consistent with premature aging and chronic degenerative disorders, in both RpWAT and pancreatic islets of daughters.—Ng, S.‐F., Lin, R. C. Y., Maloney, C. A., Youngson, N. A., Owens, J. A., Morris, M. J. Paternal high‐fat diet consumption induces common changes in the transcriptomes of retroperitoneal adipose and pancreatic islet tissues in female rat offspring. FASEB J. 28, 1830–1841 (2014). www.fasebj.org
In the last two decades, evidence from human and animal studies suggests that paternal obesity around the time of conception can have adverse effects on offspring health through developmental ...programming. This may make significant contributions to the current epidemic of obesity and related metabolic and reproductive complications like diabetes, cardiovascular disease, and subfertility/infertility. To date, changes in seminal fluid composition, sperm DNA methylation, histone composition, small non-coding RNAs, and sperm DNA damage have been proposed as potential underpinning mechanism to program offspring health. In this review, we discuss current human and rodent evidence on the impact of paternal obesity/overnutrition on offspring health, followed by the proposed mechanisms, with a focus on sperm DNA damage underpinning paternal programming. We also summarize the different intervention strategies implemented to minimize effects of paternal obesity. Upon critical review of literature, we find that obesity-induced altered sperm quality in father is linked with compromised offspring health. Paternal exercise intervention before conception has been shown to improve metabolic health. Further work to explore the mechanisms underlying benefits of paternal exercise on offspring are warranted. Conversion to healthy diets and micronutrient supplementation during pre-conception have shown some positive impacts towards minimizing the impact of paternal obesity on offspring. Pharmacological approaches e.g., metformin are also being applied. Thus, interventions in the obese father may ameliorate the potential detrimental impacts of paternal obesity on offspring.
A complex combination of adult health-related disorders can originate from developmental events that occur in utero. The periconceptional period may also be programmable. We report on the effects of ...restricting the supply of specific B vitamins (i.e., B₁₂ and folate) and methionine, within normal physiological ranges, from the periconceptional diet of mature female sheep. We hypothesized this would lead to epigenetic modifications to DNA methylation in the preovulatory oocyte and/or preimplantation embryo, with long-term health implications for offspring. DNA methylation is a key epigenetic contributor to maintenance of gene silencing that relies on a dietary supply of methyl groups. We observed no effects on pregnancy establishment or birth weight, but this modest early dietary intervention led to adult offspring that were both heavier and fatter, elicited altered immune responses to antigenic challenge, were insulin-resistant, and had elevated blood pressure-effects that were most obvious in males. The altered methylation status of 4% of 1,400 CpG islands examined by restriction landmark genome scanning in the fetal liver revealed compelling evidence of a widespread epigenetic mechanism associated with this nutritionally programmed effect. Intriguingly, more than half of the affected loci were specific to males. The data provide the first evidence that clinically relevant reductions in specific dietary inputs to the methionine/folate cycles during the periconceptional period can lead to widespread epigenetic alterations to DNA methylation in offspring, and modify adult health-related phenotypes.
Purpose
Emerging evidence from rodent studies suggests that high-fat-diet (HFD)-induced obesity is characterized by increased oxidative damage in sperm and testis. However, interventions using ...micronutrient supplementation to mitigate oxidative damage in obesity have not been extensively studied. This study aimed to investigate the effect of an antioxidant-based micronutrient supplement (added folate, vitamin B
6
, choline, betaine, and zinc) on sperm and testicular oxidative damage in HFD-fed male Sprague Dawley rats.
Methods
Rats (3-weeks-old, 12/group) were weaned onto control (C) or HFD (H) or these diets with micronutrient supplement (CS; HS); sperm and testis were harvested at 30.5 weeks. To assess oxidative stress and antioxidant capacity in testis, levels of malondialdehyde (MDA), glutathione (GSH), folate and susceptibility index (SI) of pro-oxidative damage, mRNA expression of Nrf2, NFκB-p65, IL-6, IL-10 and TNF-α, in addition to superoxide-dismutase (SOD), catalase and glutathione-peroxidase (GPx) activities were measured. 8-hydroxy-2-deoxyguanosine (8-OHdG) were assessed in both sperm and testis.
Results
HFD-fed rats had significantly increased 8-OHdG content in sperm and testis, increased testicular SI, decreased testicular weight, SOD and GPx activity compared to control. Strikingly, supplementation of HFD appeared to significantly reduce 8-OHdG in sperm and testis (22% and 24.3%, respectively), reduce testicular SI and MDA content (28% and 40%, respectively), increase testicular weight (24%), SOD and GPX activity (30% and 70%, respectively) and GSH content (19%). Moreover, supplementation had significant impact to increase testicular folate content regardless of diet. Furthermore, an overall effect of supplementation to increase testicular mRNA expression of Nrf2 was observed across groups. Interestingly, testicular SI was positively correlated with sperm and testicular 8-OHdG and MDA content, suggesting a critical role of testicular antioxidant activity to combat oxidative damage in sperm and testis.
Conclusion
Our findings suggest that antioxidant-based micronutrient supplement has the potential to interrupt HFD-induced sperm and testicular oxidative damage by improving testicular antioxidant capacity.
Graphical abstract
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.
Emerging evidence suggests that paternal obesity plays an important role in offspring health. Our previous work using a rodent model of diet-induced paternal obesity showed that female offspring from ...high-fat diet (HFD)-fed fathers develop glucose intolerance due to impairment of pancreatic insulin secretion. Here, we focused on the health outcomes of male offspring from HFD-fed fathers. Male Sprague-Dawley rats (3 wk old) were fed control (CD-F0) or HFD (HFD-F0) for 12 wk before mating with control-fed females. Male offspring were fed control diets for up to 8 wk or 6 mo. Although male offspring from HFD-F0 did not develop any obvious glucose metabolism defects in this study, surprisingly, a growth deficit phenotype was observed from birth to 6 mo of age. Male offspring from HFD-F0 had reduced birth weight compared with CD-F0, followed by reduced postweaning growth from 9 wk of age. This resulted in 10% reduction in body weight at 6 mo with significantly smaller fat pads and skeletal muscles. Reduced circulating levels of growth hormone (GH) and IGF-I were detected at 8 wk and 6 mo, respectively. Expression of adipogenesis markers was decreased in adipose tissue of HFD-F0 offspring at 8 wk and 6 mo, and expression of growth markers was decreased in muscle of HFD-F0 offspring at 8 wk. We propose that the reduced GH secretion at 8 wk of age altered the growth of male offspring from HFD-F0, resulting in smaller animals from 9 wk to 6 mo of age. Furthermore, increased muscle triglyceride content and expression of lipogenic genes were observed in HFD-F0 offspring, potentially increasing their metabolic risk.
We conducted surveillance for carbapenem-resistant Enterobacterales (CRE) during 2016–2020 at 10 US sites and extended-spectrum β-lactamase–producing Enterobacterales (ESBL-E) during 2019–2020 at 6 ...US sites. Among 159 CRE cases in children (median age 5 years), CRE was isolated from urine for 131 (82.4%) and blood from 20 (12.6%). Annual CRE incidence rate (cases/100,000 population) was 0.47–0.87. Among 207 ESBL-E cases in children (median age 6 years), ESBL-E was isolated from urine of 196 (94.7%) and blood of 8 (3.9%). Annual ESBL-E incidence rate was 26.5 in 2019 and 19.63 in 2020. CRE and ESBL-E rates were >2-fold higher among infants than other age groups. Most CRE and ESBL-E cases were healthcare-associated community-onset (68 43.0% for CRE vs. 40 23.7% for ESBL-E) or community-associated (43 27.2% for CRE vs. 109 64.5% for ESBL-E). Programs to detect, prevent, and treat multidrug-resistant infections must include pediatric populations (particularly the youngest) and outpatient settings.
The sporadic nature of Alzheimer's disease (AD) argues for an environmental link that may drive AD pathogenesis; however, the triggering factors and the period of their action are unknown. Recent ...studies in rodents have shown that exposure to lead (Pb) during brain development predetermined the expression and regulation of the amyloid precursor protein (APP) and its amyloidogenic beta-amyloid (Abeta) product in old age. Here, we report that the expression of AD-related genes APP, BACE1 (beta-site APP cleaving enzyme 1) as well as their transcriptional regulator (Sp1) were elevated in aged (23-year-old) monkeys exposed to Pb as infants. Furthermore, developmental exposure to Pb altered the levels, characteristics, and intracellular distribution of Abeta staining and amyloid plaques in the frontal association cortex. These latent effects were accompanied by a decrease in DNA methyltransferase activity and higher levels of oxidative damage to DNA, indicating that epigenetic imprinting in early life influenced the expression of AD-related genes and promoted DNA damage and pathogenesis. These data suggest that AD pathogenesis is influenced by early life exposures and argue for both an environmental trigger and a developmental origin of AD.
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