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Elucidating the mechanisms by which short chain fatty acids (SCFA) reduce body weight may assist in the development of an effective weight control strategy. Dietary supplementation of acetate, propionate, butyrate or their admixture was shown to significantly inhibit the body weight gain induced by high-fat diet feeding. Supplementation of SCFAs caused significant changes in the expressions of G-protein coupled receptor 43 (GPR43) and GPR41 characterized by increases in the adipose tissue and reductions in the colon. Additionally, they influenced the bacterial community structure in feces, with a reduction in the proportion of Firmicutes and an increase in the proportion of Bacteroidetes. The effects of dietary SCFAs on the GPR expression and gut microbiota composition may further result in body weight reduction by enhancing triglyceride hydrolysis and FFA oxidation in the adipose tissue, promoting beige adipogenesis and mitochondrial biogenesis, and inhibiting chronic inflammation.

PurposeTo investigate whether the effects of dietary folic acid supplementation on body weight gain are mediated by gut microbiota in obesity. MethodsMale C57 BL/6J conventional (CV) and germ-free (GF) mice both aged three to four weeks were fed a high-fat diet (HD), folic acid-deficient HD (FD-HD), folic acid-supplement HD (FS-HD) and a normal-fat diet (ND) for 25 weeks. Faecal microbiota were analyzed by 16S rRNA high-throughput sequencing, and the mRNA expression of genes was determined by the real-time RT-PCR. Short-chain fatty acids (SCFAs) in faeces and plasma were measured using gas chromatography–mass spectrometry.ResultsIn CV mice, HD-induced body weight gain was inhibited by FS-HD, accompanied by declined energy intake, smaller white adipocyte size, and less whitening of brown adipose tissue. Meanwhile, the HD-induced disturbance in the expression of fat and energy metabolism-associated genes (Fas, Atgl, Hsl, Ppar-α, adiponectin, resistin, Ucp2, etc.) in epididymal fat was diminished, and the dysbiosis in faecal microbiota was lessened, by FS-HD. However, in GF mice with HD feeding, dietary folic acid supplementation had almost no effect on body weight gain and the expression of fat- and energy-associated genes. Faecal or plasma SCFA concentrations in CV and GF mice were not altered by either FD-HD or FS-HD feeding.ConclusionDietary folic acid supplementation differently affected body weight gain and associated genes’ expression under HD feeding between CV and GF mice, suggesting that gut bacteria might partially share the responsibility for beneficial effects of dietary folate on obesity.

Most epidemiological and experimental studies have focused on maternal influences on offspring's health. The impact of maternal undernutrition, overnutrition, hypoxia, and stress is linked to adverse offspring outcomes across a range of systems including cardiometabolic, respiratory, endocrine, and reproduction among others. During the past decade, it has become evident that paternal environmental factors are also linked to the development of diseases in offspring. In this article, we aim to outline the current understanding of the impact of male health and environmental exposure on offspring development, health, and disease and explore the mechanisms underlying the paternal programming of offspring health. The available evidence suggests that poor paternal pre‐conceptional nutrition and lifestyle, and advanced age can increase the risk of negative outcomes in offspring, via both direct (genetic/epigenetic) and indirect (maternal uterine environment) effects. Beginning at preconception, and during utero and the early life after birth, cells acquire an epigenetic memory of the early exposure which can be influential across the entire lifespan and program a child's health. Potentially not only mothers but also fathers should be advised that maintaining a healthy diet and lifestyle is important to improve offspring health as well as the parental health status. However, the evidence is mostly based on animal studies, and well‐designed human studies are urgently needed to verify findings from animal data. Paternal exposure to environmental facts including unhealthy diets, malnutrition, and lifestyle during susceptible windows may affect offspring health, development, and chronic diseases, implicating indirect effects on the fetal component of the placenta, telomere length, sperm epigenetic, or seminal fluid protein mechanisms.

The dysregulation of NLRP3 inflammasome plays a critical role in pathogenesis of various human inflammatory diseases, thus NLRP3 inflammasome activation must be tightly controlled at multiple levels. However, the underlying mechanism regulating NLRP3 inflammasome activation remains unclear. Herein, the effects of Tripartite motif-containing protein 65 (TRIM65) on NLRP3 inflammasome activation and the underlying molecular mechanism were investigated in vitro and in vivo . Inhibition or deletion of Trim65 could significantly strengthen agonist induced NLRP3 inflammasome activation in THP-1 cells and BMDMs, indicated by increased caspase-1 activation and interleukin-1β secretion. However, TRIM65 had no effect on poly (dA: dT)-induced AIM2 inflammasome activation or flagellin-induced IPAF inflammasome activation. Mechanistically, immunoprecipitation assays demonstrated that TRIM65 binds to NACHT domain of NLRP3, promotes lys48- and lys63- linked ubiquitination of NLRP3 and restrains the NEK7-NLRP3 interaction, thereby inhibiting NLRP3 inflammasome assembly, caspase-1 activation, and IL-1β secretion. In vivo , three models of inflammatory diseases were used to confirm the suppression role of TRIM65 in NLRP3 inflammasome activation. TRIM65-deficient mice had a higher production of IL-1β induced by lipopolysaccharide in sera, and more IL-1β secretion and neutrophil migration in the ascites, and more severity of joint swelling and associated IL-1β production induced by monosodium urate, suggesting that TRIM65 deficiency was susceptible to inflammation. Therefore, the data elucidate a TRIM65-dependent negative regulation mechanism of NLRP3 inflammasome activation and provide potential therapeutic strategies for the treatment of NLRP3 inflammasome-related diseases.

Specific adipokines, such as adiponectin and resistin, are secreted from adipose tissue and are associated with the development of obesity. Supplementation of dietary SCFA can prevent and reverse high-fat-diet (HFD)-induced obesity. However, it is not clear whether SCFA ameliorate abnormal expression of adiponectin and resistin in the obese state. The aim of this study was to investigate the effects of SCFA on adiponectin and resistin’s expressions in diet-induced obese mice, as well as the potential mechanisms associated with DNA methylation. C57BL/6J male mice were fed for 16 weeks with five types of HFD (34·9 % fat by wt., 60 % kJ) – a control HFD and four HFD with acetate (HFD-A), propionate (HFD-P), butyrate (HFD-B) and their admixture (HFD-SCFA). Meanwhile, a low-fat diet (4·3 % fat by wt., 10 % kJ) was used as the control group. The reduced mRNA levels of adiponectin and resistin in the adipose tissue of the HFD-fed mice were significantly reversed by dietary supplementation of acetate, propionate, butyrate or their admixture to the HFD. Moreover, the expressional changes of adiponectin and resistin induced by SCFA were associated with alterations in DNA methylation at their promoters, which was mediated by reducing the expressions of enzyme-catalysed DNA methyltransferase ( DNMT1 , 3a , 3b ) and the methyl-CpG-binding domain protein 2 ( MBD2 ) and suppressing the binding of these enzymes to the promoters of adiponectin and resistin. Our results indicate that SCFA may correct aberrant expressions of adiponectin and resistin in obesity by epigenetic regulation.

Background Early-life antibiotic exposure is associated with the development of later obesity through the disruption of gut microbiota in the animal models. However, the related epidemiological evidence is still conflicting. Methods A birth cohort was consisted of 2140 mother-infant pairs in Chaoyang District Maternal and Child Health Care Hospital in this study. Here, their available antibiotic exposure during the first one year of life was ascertained using a open-ended questionnaire and related anthropometric parameters from the health screening program. The compositions of gut microbiota were comprehensively analyzed by16S rRNA high throughput sequencing. Then the spearman correlations were performed by the multiple covariance-adjusted regressions between the antibiotic exposure with anthropometric parameters and compositions of gut microbiota. Results Among the 2140 subjects, the antibiotic exposure during the first one year of life was 53.04%, mainly by Cephalosporins (53.39%) and Erythromycins(27.67%) for the treatment of respiratory tract infection (79.56%), which were not significantly different among the subgroups. Compared to the control group, both childhood overweight and obesity at two and a half years were higher in the antibiotic exposed group, with higher percents of Faecalibacterium , Agathobacter and Klebsiella , and lower percentage of Bifidobacterium . Moreover, there were positively potential associations between early-life antibiotic exposure with the accelerated anthropometric parameters and disruption of Faecalibacterium , Agathobacter , Klebsiella and Bifidobacterium at two and a half years. Conclusion These above results proved that early-life antibiotic exposure was positively associated with the accelerated childhood overweight and obesity from one year to two and a half years by impacting the disorders of Faecalibacterium, Agathobacter, Klebsiella and Bifidobacterium , which would propose the theoretical basis for rationalizing the personalized antibiotic exposure among the infants to truly reflect the fairness of public health.

Background Telomeres play a crucial role in cellular survival and its length is a predictor for onset of chronic non-communicable diseases. Studies on association between telomeres and obesity in children have brought discrepant results and the underlying mechanisms and influential factors are to be elucidated. This study aimed to investigate changes in telomere length and telomerase reverse transcriptase (TERT) DNA methylation, and further to determine their correlation with n-3 polyunsaturated fatty acids (PUFAs) in preschool children with obesity. Methods Forty-six preschool children with obesity aged 3 to 4 years were included in the study, with equal numbers of age- and gender-matched children with normal weight as control. Leukocyte telomere length was determined by the ratio of telomeric product and single copy gene obtained using real-time qPCR. DNA methylation of TERT promoter was analyzed by bisulfite sequencing. Fatty acids in erythrocytes were measured by gas chromatography with a total of 15 fatty acids analyzed. The total saturated fatty acids (SFAs), total n-6 PUFAs, total n-3 PUFAs, and the ratio of arachidonic acid (AA) to docosahexaenoic acid (DHA) were calculated. Then the correlation between leukocyte telomere length, TERT promoter methylation and fatty acids was determined. Results In preschool children with obesity, leukocyte telomeres were shortened and had a negative association with the body mass index. The methylated fractions in 13 of 25 CpG sites in the TERT promoter were increased by approximately 3 to 35% in the children with obesity compared to the normal weight children. Erythrocyte lauric acid and total SFAs, lenoleic acid and total n-6 PUFAs were higher, and DHA was lower in the children with obesity than those in the children with normal weight. Correlative analysis showed that leukocyte telomere length had a positive association with total SFAs and DHA, and a negative association with the AA/DHA ratio. However, no association between erythrocyte DHA and the TERT promoter methylation was found. Conclusion These data indicate that the reduced body DHA content and increased AA/DHA ratio may be associated with shortened leukocyte telomeres in child obesity, which is probably not involved in the TERT promoter methylation.

Background RNA-binding proteins (RBPs) have been proved to play essential roles in post-transcriptional regulation of genes associated with adipogenesis. However, the role of the RBP human antigen R (HuR) in the pathogenesis of obesity remains to be clarified. Methods Adipocyte-specific HuR knockout (HuR −/− ) and HuR floxed (HuR f/f ) mice were fed a high-fat diet (HFD), or a paired normal control diet (NC) for 16 weeks. Moreover, 8-week-old HuR −/− or HuR f/f mice were subjected to cold exposure or CL316,243 treatments. The mouse body weight was recorded and the histological changes in adipose tissue were examined. RNA sequencing analysis and RT-qPCR were used to identify potential target genes for HuR. The regulation of HuR on the uncoupling protein 1 (Ucp1) expression was determined using RNA immunoprecipitation (RIP), RNA pull-down, and Luciferase assays. Results Adipocyte-specific HuR deletion inhibited body weight gain with HFD feeding, being accompanied by less BAT whitening and more WAT browning, and up-regulated expressions of adipose thermogenic genes (Pgc-1α, Ucp1, etc.). HuR could bind to the 3’UTR of the Ucp1 mRNA, and thus downregulated its expression. In addition, although the HuR expression was not changed in obesity, there was an enhanced transfer of HuR protein from the nuclear to cytoplasm, thus impacting the expression of target genes including the Ucp1. Conclusions These findings indicate that adipose tissue-specific HuR deletion alleviates HFD-induced obesity by promoting adipose thermogenesis through upregulating Ucp1 expression.

This research focused on the characterization of sediment-derived dissolved organic matter (SDOM) extracted from sediment of Yellow River and the binding behaviors of ceftazidime (CAZ) with the presence of SDOM. The morphology, surface composition and structure of SDOM and the complexation between SDOM and CAZ in terms of component features, binding capacity and sequence were studied by multiple approaches. Results showed that SDOM was in situ autochthonous-dominated with a low weight-average molecular weight and aromaticity (the value of S R was 2.523). The multiple morphological characteristics, high surface oxygen contents (53.49%) and more aliphatic (H/C = 1.91) of SDOM were further confirmed. Studies on SDOM-CAZ interaction suggested that the functional groups and chemical compositions of SDOM were susceptible to CAZ. In more detail, the aromatic protons and aliphatic protons of CAZ impacted significantly, and the binding between CAZ and SDOM might relate to noncovalent. The protein-like fractions were considered to be the primary participant with 49% fractions lost and the aromatics and amides as mainly active site interaction with CAZ. These findings have significant implications on the environmental fate of cephalosporin antibiotics and that of sediment-derived DOM.

Background Serum iron biomarkers are disordered on the progression of obesity and its associated metabolic syndrome (MetS). However, limited evidence is explored the interactions between serum iron biomarkers and the incidence of MetS. Thus, the purpose of this study is to discuss whether epigenetic modifications of nuclear and mitochondrial DNA (mtDNA) are associated with the disturbance of serum iron biomarkers among the metabolically unhealthy obesity (MUO) school-age children. Methods A representative cross-sectional study was performed using the data from 104 obesity school-age children, while the subjects without obesity were as controls ( n  = 65). Then, the 104 obesity subjects were defined as metabolically healthy obesity (MHO, n  = 60) and MUO ( n  = 44) subgroups according to whether they were accompanied with MetS. Their serum metabolic indicators, transferrin receptor 1 (TFR1), transferrin (TF) and genome-wide methylation were determined by the Elisa method. Moreover, the methylation levels of TFR1 and TF were measured by the Bisulfite sequencing PCR (BSP-PCR). Furthermore, the copy number (mtDNA-CN) and methylation of mtDNA were detected by the RT-PCR, while the semi-long RT-PCR was then used to estimate the lesions of mtDNA. Results Compared with the control and MHO groups, the levels of MetS related indicators, anthropological characteristics and 8-OHdG were higher, and the concentrations of CAT, GSH-Px, TF, TFR1 and genome-wide methylation were lower in the MUO group in a BMI-independent manner ( P  < 0.05). Then, the contents of serum iron were lower in both the MHO and MUO groups than those in the control group ( P  < 0.017). Moreover, they were positively related with the contents of serum CAT and GSH-Px, and negatively with 8-OHdG, TF and TFR1 ( P  < 0.05). Furthermore, the methylation patterns on the TF, TFR1 and mtDNA were higher in the MUO group than those in the MHO and control groups ( P  < 0.017), which were negatively correlated with their serum contents ( P  < 0.05). Meanwhile, the ratio of methylated/unmethylated mtDNA was significantly associated with their mtDNA-CN and lesions ( P  < 0.05). Conclusions Our findings suggested that the impairments on the epigenetic modifications of nuclear (genome-wide DNA, TF and TFR1) and mtDNA were associated with the disturbance of serum iron biomarkers to involve in the pathophysiology of MetS among the school-age MUO children. Trial registration This study was approved by the Ethics Committee of Beijing Children’s Hospital affiliated to Capital Medical University (No. IEC-C−006-A04-V.06), which was also registered at the website of http://www.chictr.org.cn/showproj.aspx?proj=4673 (No: ChiCTR-OCH−14004900).