EPIGENOMICS AND METABOLOMICS MECHANISMS FOR A GENE X DIET INTERACTION MODULATING AGE-RELATED OBESITY
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ABSTRACT:
SUBMITTER: Smith C
PROVIDER: S-EPMC6227257 | biostudies-literature | 2018 Nov
REPOSITORIES: biostudies-literature
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Project description:BackgroundThe putative functional variant -265T>C (rs5082) within the APOA2 promoter has shown consistent interactions with saturated fatty acid (SFA) intake to influence the risk of obesity.ObjectiveThe aim of this study was to implement an integrative approach to characterize the molecular basis of this interaction.DesignWe conducted an epigenome-wide scan on 80 participants carrying either the rs5082 CC or TT genotypes and consuming either a low-SFA (<22 g/d) or high-SFA diet (≥22 g/d), matched for age, sex, BMI, and diabetes status in the Boston Puerto Rican Health Study (BPRHS). We then validated the findings in selected participants in the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) Study (n = 379) and the Framingham Heart Study (FHS) (n = 243). Transcription and metabolomics analyses were conducted to determine the relation between epigenetic status, APOA2 mRNA expression, and blood metabolites.ResultsIn the BPRHS, we identified methylation site cg04436964 as exhibiting significant differences between CC and TT participants consuming a high-SFA diet, but not among those consuming low-SFA. Similar results were observed in the GOLDN Study and the FHS. Additionally, in the FHS, cg04436964 methylation was negatively correlated with APOA2 expression in the blood of participants consuming a high-SFA diet. Furthermore, when consuming a high-SFA diet, CC carriers had lower APOA2 expression than those with the TT genotype. Lastly, metabolomic analysis identified 4 pathways as overrepresented by metabolite differences between CC and TT genotypes with high-SFA intake, including tryptophan and branched-chain amino acid (BCAA) pathways. Interestingly, these pathways were linked to rs5082-specific cg04436964 methylation differences in high-SFA consumers.ConclusionsThe epigenetic status of the APOA2 regulatory region is associated with SFA intake and APOA2 -265T>C genotype, promoting an APOA2 expression difference between APOA2 genotypes on a high-SFA diet, and modulating BCAA and tryptophan metabolic pathways. These findings identify potential mechanisms by which this highly reproducible gene-diet interaction influences obesity risk, and contribute new insights to ongoing investigations of the relation between SFA and human health. This study was registered at clinicaltrials.gov as NCT03452787.
| S-EPMC6454512 | biostudies-literature
Project description:The rapid rise of obesity during the past decades has coincided with a profound shift of our living environment, including unhealthy dietary patterns, a sedentary lifestyle, and physical inactivity. Genetic predisposition to obesity may have interacted with such an obesogenic environment in determining the obesity epidemic. Growing studies have found that changes in adiposity and metabolic response to low-calorie weight loss diets might be modified by genetic variants related to obesity, metabolic status and preference to nutrients. This review summarized data from recent studies of gene-diet interactions, and discussed integration of research of metabolomics and gut microbiome, as well as potential application of the findings in precision nutrition.
| S-EPMC5412371 | biostudies-literature
Project description:Age-related macular degeneration (AMD) leads to irreversible visual loss, therefore, early intervention is desirable, but due to its multifactorial nature, diagnosis of early disease might be challenging. Identification of early markers for disease development and progression is key for disease diagnosis. Suitable biomarkers can potentially provide opportunities for clinical intervention at a stage of the disease when irreversible changes are yet to take place. One of the most metabolically active tissues in the human body is the retina, making the use of hypothesis-free techniques, like metabolomics, to measure molecular changes in AMD appealing. Indeed, there is increasing evidence that metabolic dysfunction has an important role in the development and progression of AMD. Therefore, metabolomics appears to be an appropriate platform to investigate disease-associated biomarkers. In this review, we explored what is known about metabolic changes in the retina, in conjunction with the emerging literature in AMD metabolomics research. Methods for metabolic biomarker identification in the eye have also been discussed, including the use of tears, vitreous, and aqueous humor, as well as imaging methods, like fluorescence lifetime imaging, that could be translated into a clinical diagnostic tool with molecular level resolution.
| S-EPMC6358913 | biostudies-other
Project description:Obesity is associated with low-grade inflammation that leads to insulin resistance and type 2 diabetes via Toll-like Receptor (TLR) and TNF-family cytokine receptor (TNFR) signaling pathways. Ubc13 is an ubiquitin-conjugating enzyme responsible for non-canonical K63-linked polyubiquitination of TNF receptor-associated factor (TRAF)-family adapter proteins involved in TLR and TNFR pathways. However, the relationship between Ubc13 and metabolic disease remains unclear. In this study, we investigated the role of Ubc13 in insulin resistance and high-fat diet (HFD)-induced obesity. We compared wild-type (WT) and Ubc13 haploinsufficient (ubc13(+/-)) mice under normal diet (ND) and HFD, since homozygous knockout mice (ubc13(-/-)) are embryonic lethal. Male and female ubc13(+/-) mice were protected against age-related insulin resistance under ND and HFD compared to WT mice. Interestingly, only female ubc13(+/-) mice were protected against HFD-induced obesity and hepatic steatosis. Moreover, only female HFD-fed ubc13(+/-) mice showed lower expression of inflammatory cytokines that was secondary to reduction in weight gain not present in the other groups. In summary, our results indicate that suppression of Ubc13 activity may play a metabolic role independent of its inflammatory function. Thus, Ubc13 could represent a therapeutic target for insulin resistance, diet-induced obesity, and associated metabolic dysfunctions.
| S-EPMC5086849 | biostudies-other
Project description:Affective and substance-use disorders are associated with overweight and obesity-related complications, which are often due to the overconsumption of palatable food. Both high-fat diets (HFDs) and psychostimulant drugs modulate the neuro-circuitry regulating emotional processing and metabolic functions. However, it is not known how they interact at the behavioural level, and whether they lead to overlapping changes in neurobiological endpoints. In this literature review, we describe the impact of HFDs on emotionality, cognition, and reward-related behaviour in rodents. We also outline the effects of HFD on brain metabolism and plasticity involving mitochondria. Moreover, the possible overlap of the neurobiological mechanisms produced by HFDs and psychostimulants is discussed. Our in-depth analysis of published results revealed that HFDs have a clear impact on behaviour and underlying brain processes, which are largely dependent on the developmental period. However, apart from the studies investigating maternal exposure to HFDs, most of the published results involve only male rodents. Future research should also examine the biological impact of HFDs in female rodents. Further knowledge about the molecular mechanisms linking stress and obesity is a crucial requirement of translational research and using rodent models can significantly advance the important search for risk-related biomarkers and the development of clinical intervention strategies.
| S-EPMC9317076 | biostudies-literature
Project description:The gut microbiota is important in the occurrence and development of obesity. It can not only via its metabolites, but also through microbiota-gut-brain-liver interactions, directly or indirectly, influence obesity. Quinoa, known as one kind of pseudocereals and weight loss food supplements, has been high-profile for its high nutritional value and broad applications. In this context, we produced high-fat diet-induced (HFD) obese mouse models and assessed the efficacy of quinoa with saponin and quinoa without saponin on obesity. We explored the potential therapeutic mechanisms of quinoa using methods such as 16S rRNA, Western blotting, Immunohistochemical (IHC). Our results indicated that quinoa can improve the obese symptoms significantly on HFD mice, as well as aberrant glucose and lipid metabolism. Further analyses suggest that quinoa can regulate microbiota in the colon and have predominantly regulation on Bacteroidetes, Actinobacteria and Desulfovibrio, meanwhile can decrease the F/B ratio and the abundance of Blautia. Contemporaneously, quinoa can upregulate the expression of TGR5 in the colon and brain, as well as GLP-1 in the colon, liver and brain. while downregulate the expression of TLR4 in the colon and liver, as well as markers of ER stress and oxidative stress in livers and serums. Beyond this, tight junctional proteins in colons and brains are also increased in response to quinoa. Therefore, quinoa can effectively reduce obesity and may possibly exert through microbiota-gut-brain-liver interaction mechanisms. IMPORTANCE Gut microbiota has been investigated extensively, as a driver of obesity as well as a therapeutic target. Studies of its mechanisms are predominantly microbiota-gut-brain axis or microbiota-gut-liver axis. Recent studies have shown that there is an important correlation between the gut-brain-liver axis and the energy balance of the body. Our research focus on microbiota-gut-brain-liver axis, as well as influences of quinoa in intestinal microbiota. We extend this study to the interaction between microbiota and brains, and the result shows obvious differences in the composition of the microbiome between the HFD group and others. These observations infer that besides the neurotransmitter and related receptors, microbiota itself may be a mediator for regulating bidirectional communication, along the gut-brain-liver axis. Taken together, these results also provide strong evidence for widening the domain of applicability of quinoa.
| S-EPMC9241864 | biostudies-literature
Project description:Background & aimsThe nutrition transition in developing countries like Iran causes the increasing rise of obesity and abdominal obesity rates. However, it is not yet well proven that environmental modifications like improving the quality of beverage intake can be effective in people who have a genetic predisposition to obesity. So, in the present study, we examine the interaction between genetic predisposition and healthy beverage index (HBI) with abdominal obesity and obesity-related metabolic risk factors in overweight and obese women.MethodBased on inclusion and exclusion criteria, 202 overweight or obese females were chosen for this cross-sectional study. Body composition, anthropometric measures, physical activity, and beverage intake data were collected and analyzed using recognized and trustworthy methodologies. Biochemical tests were performed on serum samples. A genetic risk score (GRS) was calculated based on the results of genetic tests. The predetermined HBI was calculated based on previous studies. A generalized linear model was used to estimate the interactions between GRS and HBI (GLM).ResultsWe found significant interactions between GRS and HBI on WHR (β = - 0.39, CI: -0.07 to 0.001, P = 0.05) and WC (β = - 6.18, CI: - 13.41 to 1.05, P = 0.09). Also, there were significant gene-diet interactions for HBI and GRS on HDL (β = 7.09, CI: - 0.73 to 14.92, P = 0.07) and FBS (β = - 9.07, CI: - 18.63 to 0.47, P = 0.06).ConclusionsThese findings emphasize the HBI considering genetics appears to protect against the risks of abdominal obesity and metabolic associated obesity markers.
| S-EPMC9516810 | biostudies-literature
Project description:BackgroundVenomous organisms serve as wonderful systems to study the evolution and expression of genes that are directly associated with prey capture. To evaluate the relationship between venom gene expression and prey utilization, we examined these features among individuals of different ages of the venomous, worm-eating marine snail Conus ebraeus. We determined expression levels of six genes that encode venom components, used a DNA-based approach to evaluate the identity of prey items, and compared patterns of venom gene expression and dietary specialization.ResultsC. ebraeus exhibits two major shifts in diet with age-an initial transition from a relatively broad dietary breadth to a narrower one and then a return to a broader diet. Venom gene expression patterns also change with growth. All six venom genes are up-regulated in small individuals, down-regulated in medium-sized individuals, and then either up-regulated or continued to be down-regulated in members of the largest size class. Venom gene expression is not significantly different among individuals consuming different types of prey, but instead is coupled and slightly delayed with shifts in prey diversity.ConclusionThese results imply that changes in gene expression contribute to intraspecific variation of venom composition and that gene expression patterns respond to changes in the diversity of food resources during different growth stages.
| S-EPMC4730619 | biostudies-literature
Project description:Akt1 is a serine/threonine kinase that promotes cell growth and survival. Previously, Akt1 activation in a double transgenic (DTG) mouse model fed a high-fat/high-sucrose (HF/HS) diet was found to promote type IIb muscle growth and to lead to a significant reduction in obesity. Here, we have used metabolomics to examine the metabolic perturbations in blood serum and liver and gastrocnemius tissues of the DTG mice. Multivariate statistics highlighted consistent metabolic changes in gastrocnemius muscle following Akt1 activation, which included significant reductions of serine and histidine-containing dipeptides (anserine and carnosine), in addition to increased concentrations of phosphorylated sugars. In addition, Akt1-mediated regression in obesity could be associated with increased glycolysis in gastrocnemius muscle as well as increased gluconeogenesis, glycogenolysis, and ketogenesis in the liver. In old DTG animals, Akt1 activation was found to improve glucose metabolism and confer a beneficial effect in the regression of age-related fat accumulation. This study identifies metabolic changes induced by Akt1-mediated muscle growth and demonstrates a cross-talk between distant organs that leads to a regression of fat mass. The current findings indicate that agents that promote Akt1 induction in muscle have utility in the regression of obesity.
| S-EPMC4286153 | biostudies-other
Project description:The American Diabetes Association convened a research symposium, "Epigenetics and Epigenomics: Implications for Diabetes and Obesity" on 17-19 November 2017. International experts in genetics, epigenetics, computational biology, and physiology discussed the current state of understanding of the relationships between genetics, epigenetics, and environment in diabetes and examined existing evidence for the role of epigenetic factors in regulating metabolism and the risk of diabetes and its complications. The authors summarize the presentations, which highlight how the complex interactions between genes and environment may in part be mediated through epigenetic changes and how information about nutritional and other environmental stimuli can be transmitted to the next generation. In addition, the authors present expert consensus on knowledge gaps and research recommendations for the field.
| S-EPMC6463748 | biostudies-literature