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A Metabolomic Approach to Understanding the Metabolic Link between Obesity and Diabetes.

ABSTRACT: Obesity and diabetes arise from an intricate interplay between both genetic and environmental factors. It is well recognized that obesity plays an important role in the development of insulin resistance and diabetes. Yet, the exact mechanism of the connection between obesity and diabetes is still not completely understood. Metabolomics is an analytical approach that aims to detect and quantify small metabolites. Recently, there has been an increased interest in the application of metabolomics to the identification of disease biomarkers, with a number of well-known biomarkers identified. Metabolomics is a potent approach to unravel the intricate relationships between metabolism, obesity and progression to diabetes and, at the same time, has potential as a clinical tool for risk evaluation and monitoring of disease. Moreover, metabolomics applications have revealed alterations in the levels of metabolites related to obesity-associated diabetes. This review focuses on the part that metabolomics has played in elucidating the roles of metabolites in the regulation of systemic metabolism relevant to obesity and diabetes. It also explains the possible metabolic relation and association between the two diseases. The metabolites with altered profiles in individual disorders and those that are specifically and similarly altered in both disorders are classified, categorized and summarized.

SUBMITTER: Park S

PROVIDER: S-EPMC4507023 | biostudies-other | 2015 Jul

REPOSITORIES: biostudies-other

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A Metabolomic Approach to Understanding the Metabolic Link between Obesity and Diabetes.

Park Seokjae S Sadanala Krishna Chaitanya KC Kim Eun-Kyoung EK

Molecules and cells 20150615 7

Obesity and diabetes arise from an intricate interplay between both genetic and environmental factors. It is well recognized that obesity plays an important role in the development of insulin resistance and diabetes. Yet, the exact mechanism of the connection between obesity and diabetes is still not completely understood. Metabolomics is an analytical approach that aims to detect and quantify small metabolites. Recently, there has been an increased interest in the application of metabolomics to ...[more]

PMID: 26072981

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Project description:BACKGROUND:Obesity is a well-known risk factor for elevated inflammation and insulin resistance. Social anxiety may moderate this relationship, such that individuals who areboth obese and socially anxious may have an even greater risk for elevated inflammation and insulin resistance than those who are obese but not socially anxious; the combination of obesity and social anxiety is markedly stressful. METHODS:The current paper reports secondary analyses from the Biomarker wave of the Mid-Life in the United States (MIDUS) study (N?=?1255), a publicly available dataset of American adults. Participants completed a standard scale measuring social anxiety symptoms and had their waist circumference, height, and weight measured by a staff member. They also provided a fasting blood sample that was assayed for CRP, IL-6, HOMA-IR, glucose, and insulin. RESULTS:The interaction between obesity and social anxiety symptoms was significant. People with a larger waist circumference and more social anxiety symptoms had greater inflammation and insulin resistance relative to those with a larger waist circumference but less social anxiety symptoms. These results were similar for both measures of inflammation and were robust across both the unadjusted and adjusted models. The results were also largely replicated in models using body mass index (BMI) rather than waist circumference as the measure of obesity. CONCLUSIONS:The current findings build on existing work about the health risks of obesity, extending it in an important new direction by demonstrating that these health risks are stronger among those who are also socially anxious. In fact, the magnitude of the relationship between obesity and metabolic function is 1.5 times stronger among those with more social anxiety symptoms. Thus, knowing whether a person is obese only provides one piece of the puzzle; knowing information about both obesity and social anxiety symptoms is critical for understanding who is most at risk for obesity-related health problems. Thus, a critical next step is for intervention scientists to examine health programs tailored to people who are both obese and socially anxious.

Project description:The risk of metabolic diseases is greatly increased by both chronic and acute stress. Irrespective of the cause, chronic or acute stress has the capacity to alter an individual's cytokine profile. For instance, it has been observed that stress significantly increased concentrations of IL 1 beta, IL 6 and TNF alpha. Alteration in cytokine profiles increase the likelihood of dysregulated metabolism, which subsequently acts as a driving force in the development of disorders, such as cardiovascular disease (CVD), hypertension, diabetes and obesity. Considering the dynamic and versatile role of cytokines in health and disease, an in-depth computational analysis (qualitative and quantitative) was performed to study the role of cytokines as an immuno-molecular link between rising stress levels and an increase in CVD, hypertension, diabetes and obesity. Upon a qualitative comparative analysis of cytokine profiles, a total of 14 cytokines (IL-6, TNF-alpha, IFN-gamma, IL-10, etc.) were observed to be commonly involved in stress and aforementioned four metabolic disorders. Further analysis of quantitative studies has revealed that the cytokine profile for coronary artery disease (CAD) showed remarkable increase in a couple of cytokines. IL 9 registered an increase of 67 percent to reach a concentration of 75 pg/mL. IL 3, on the other hand, was absent in control candidates but reached 56 ± 14 pg/mL in CAD patients. In case of diabetes, IFN-gamma showed an increase of 290 pg/mL. For obesity it was observed that both MCP-1 and IL-1 beta fell by 12.2 pg/mL to reach 44.4 pg/mL in obese patients. A fall of approximately 50 pg/mL was observed in the concentration of VEGF in obese patients. Similarly, hypertension was marked by reduction in concentration of several cytokines - MCP-1 and VEGF being a couple of them. Apart from performing an analysis of cytokine profiles, an innovative database [Cytokine database of Stress and Metabolic disorders (CdoSM)-https://www.akbi-nsut.co.in/] has also been created comprising cytokines involved in stress and the aforementioned metabolic disorders. Upon accessing the database, a user can find the list cytokines associated with a particular condition along with information on cytokine receptor/s; related research articles; cytokine concentration in control v/s diseased candidates for some specific cytokines and the Uniprot ID for the respective cytokine. Database can be accessed by the link-https://www.akbi-nsut.co.in/.Supplementary informationThe online version contains supplementary material available at 10.1007/s13205-022-03375-0.

Project description:BackgroundMetabolic syndrome (MS) is a construct used to separate "healthy" from "unhealthy" obese patients, and is a major risk factor for type 2 diabetes (T2D) and cardiovascular disease. There is controversy over whether obese "metabolically well" persons have a higher morbidity and mortality than lean counterparts, suggesting that MS criteria do not completely describe physiologic risk factors or consequences of obesity. We hypothesized that metabolomic analysis of plasma would distinguish obese individuals with and without MS and T2D along a spectrum of obesity-associated metabolic derangements, supporting metabolomic analysis as a tool for a more detailed assessment of metabolic wellness than currently used MS criteria.MethodsFasting plasma samples from 90 adults were assigned to groups based on BMI and ATP III criteria for MS: (1) lean metabolically well (LMW; n = 24); (2) obese metabolically well (OBMW; n = 26); (3) obese metabolically unwell (OBMUW; n = 20); and (4) obese metabolically unwell with T2D (OBDM; n = 20). Forty-one amino acids/dipeptides, 33 acylcarnitines and 21 ratios were measured. Obesity and T2D effects were analyzed by Wilcoxon rank-sum tests comparing obese nondiabetics vs LMW, and OBDM vs nondiabetics, respectively. Metabolic unwellness was analyzed by Jonckheere-Terpstra trend tests, assuming worsening health from LMW ? OBMW ? OBMUW. To adjust for multiple comparisons, statistical significance was set at p < 0.005. K-means cluster analysis of aggregated amino acid and acylcarnitine data was also performed.ResultsAnalytes and ratios significantly increasing in obesity, T2D, and with worsening health include: branched-chain amino acids (BCAAs), cystine, alpha-aminoadipic acid, phenylalanine, leucine + lysine, and short-chain acylcarnitines/total carnitines. Tyrosine, alanine and propionylcarnitine increase with obesity and metabolic unwellness. Asparagine and the tryptophan/large neutral amino acid ratio decrease with T2D and metabolic unwellness. Malonylcarnitine decreases in obesity and 3-OHbutyrylcarnitine increases in T2D; neither correlates with unwellness. Cluster analysis did not separate subjects into discreet groups based on metabolic wellness.DiscussionLevels of 15 species and metabolite ratios trend significantly with worsening metabolic health; some are newly recognized. BCAAs, aromatic amino acids, lysine, and its metabolite, alpha-aminoadipate, increase with worsening health. The lysine pathway is distinct from BCAA metabolism, indicating that biochemical derangements associated with MS involve pathways besides those affected by BCAAs. Even those considered "obese, metabolically well" had metabolite levels which significantly trended towards those found in obese diabetics. Overall, this analysis yields a more granular view of metabolic wellness than the sole use of cardiometabolic MS parameters. This, in turn, suggests the possible utility of plasma metabolomic analysis for research and public health applications.

Dataset Information

A Metabolomic Approach to Understanding the Metabolic Link between Obesity and Diabetes.

Publications

A Metabolomic Approach to Understanding the Metabolic Link between Obesity and Diabetes.

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