Plasma Bile Acid Profile in Patients with and without Type 2 Diabetes

Mantovani, Alessandro; Dalbeni, Andrea; Peserico, Denise; Cattazzo, Filippo; Bevilacqua, Michele; Salvagno, Gian Luca; Lippi, Giuseppe; Targher, Giovanni; Danese, Elisa; Fava, Cristiano

doi:10.3390/metabo11070453

Cited by 40 publications

(25 citation statements)

References 25 publications

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“…However, as compared with the HFHS group, the sDM monkeys failed to increase some bile acid species, including hyodeoxycholic acid, a bile acid of importance in regulating glucose homeostasis ( Zheng et al, 2021b ). In contrast, the sDM subjects had higher levels of taurocholic acid and taurodeoxycholic acid in both the liver and HPVB, which was also observed in the plasma of human patients ( Mantovani et al, 2021 ). These observations suggest that distinct metabolic signatures of sDM and HFHS monkeys can be revealed by metabolomics and lipidomics, although some tendencies of bile acid changes in the prediabetic models were similar to those in the monkeys of diabetes.…”

Section: Resultsmentioning

confidence: 89%

Multi-Omics Comparison of the Spontaneous Diabetes Mellitus and Diet-Induced Prediabetic Macaque Models

Yang

Tan

et al. 2021

Front. Pharmacol.

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The prevalence of diabetes mellitus has been increasing for decades worldwide. To develop safe and potent therapeutics, animal models contribute a lot to the studies of the mechanisms underlying its pathogenesis. Dietary induction using is a well-accepted protocol in generating insulin resistance and diabetes models. In the present study, we reported the multi-omics profiling of the liver and sera from both peripheral blood and hepatic portal vein blood from Macaca fascicularis that spontaneously developed Type-2 diabetes mellitus with a chow diet (sDM). The other two groups of the monkeys fed with chow diet and high-fat high-sugar (HFHS) diet, respectively, were included for comparison. Analyses of various omics datasets revealed the alterations of high consistency. Between the sDM and HFHS monkeys, both the similar and unique alterations in the lipid metabolism have been demonstrated from metabolomic, transcriptomic, and proteomic data repeatedly. The comparison of the proteome and transcriptome confirmed the involvement of fatty acid binding protein 4 (FABP4) in the diet-induced pathogenesis of diabetes in macaques. Furthermore, the commonly changed genes between spontaneous diabetes and HFHS diet-induced prediabetes suggested that the alterations in the intra- and extracellular structural proteins and cell migration in the liver might mediate the HFHS diet induction of diabetes mellitus.

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Section: Resultsmentioning

confidence: 89%

Multi-Omics Comparison of the Spontaneous Diabetes Mellitus and Diet-Induced Prediabetic Macaque Models

Yang

Tan

et al. 2021

Front. Pharmacol.

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“…Similar results were observed by Higgins et al ( 66 ), reporting that obese adolescents had reduced postprandial plasma BA concentrations in comparison to lean controls, despite similar fasting BA levels. Mantovani et al ( 67 ) demonstrated also that postprandial BA concentrations were distinctly different between healthy and diabetic individuals ( 66 , 67 ). Since BA concentrations in plasma increased similar in both clusters in the initial phase of the OGTT ( Figure 1 ) their absorption from the intestine seems not to be different between cluster.…”

Section: Discussionmentioning

confidence: 99%

Plasma Metabolic Signatures of Healthy Overweight Subjects Challenged With an Oral Glucose Tolerance Test

et al. 2022

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Insulin secretion following ingestion of a carbohydrate load affects a multitude of metabolic pathways that simultaneously change direction and quantity of interorgan fluxes of sugars, lipids and amino acids. In the present study, we aimed at identifying markers associated with differential responses to an OGTT a population of healthy adults. By use of three metabolite profiling platforms, we assessed these postprandial responses of a total of 202 metabolites in plasma of 72 healthy volunteers undergoing comprehensive phenotyping and of which half enrolled into a weight-loss program over a three-month period. A standard oral glucose tolerance test (OGTT) served as dietary challenge test to identify changes in postprandial metabolite profiles. Despite classified as healthy according to WHO criteria, two discrete clusters (A and B) were identified based on the postprandial glucose profiles with a balanced distribution of volunteers based on gender and other measures. Cluster A individuals displayed 26% higher postprandial glucose levels, delayed glucose clearance and increased fasting plasma concentrations of more than 20 known biomarkers of insulin resistance and diabetes previously identified in large cohort studies. The volunteers identified by canonical postprandial responses that form cluster A may be called pre-pre-diabetics and defined as “at risk” for development of insulin resistance. Moreover, postprandial changes in selected fatty acids and complex lipids, bile acids, amino acids, acylcarnitines and sugars like mannose revealed marked differences in the responses seen in cluster A and cluster B individuals that sustained over the entire challenge test period of 240 min. Almost all metabolites, including glucose and insulin, returned to baseline values at the end of the test (at 240 min), except a variety of amino acids and here those that have been linked to diabetes development. Analysis of the corresponding metabolite profile in a fasting blood sample may therefore allow for early identification of these subjects at risk for insulin resistance without the need to undergo an OGTT.

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“…Elevated concentrations of short-chain acylcarnitines have been linked to insulin resistance [38]. A bile acid, glycodeoxycholic acid, has been associated with increased risk of type 2 diabetes [39]. Our previous study based on the METSIM cohort showed that tyrosine, aspartate, and glutamate were significantly associated with decreases in insulin sensitivity and insulin secretion and consequently with increased risk of type 2 diabetes [15].…”

Section: Discussionmentioning

confidence: 99%

Metabolite Signature of Physical Activity and the Risk of Type 2 Diabetes in 7271 Men

et al. 2022

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Large population-based studies investigating the association of physical activity (PA) with the metabolite signature contribute significantly to the understanding of the effects of PA on metabolic pathways associated with the risk of type 2 diabetes. Our study included 8749 Finnish men without diabetes at baseline recruited from the Metabolic Syndrome in Men (METSIM) cohort. We used a questionnaire to measure leisure-time PA. Metabolites were measured in 7271 men as a part of Metabolon’s untargeted Discovery HD4 platform using ultrahigh-performance liquid chromatography–tandem mass spectrometry. We found 198 metabolites significantly associated with PA. Several of these metabolites were novel including especially steroids, amino acids, imidazoles, carboxylic acids, and hydroxy acids. Increased PA was significantly associated with high levels of choline plasmalogens, lysophosphatidylcholines, polyunsaturated fatty acids, carotenoids, long chain acylcarnitines, imidazoles, bilirubins, aryl sulfates, hydroxy acids, indolepropionate, and indolelactate. Several of these metabolites have been previously associated with a decreased risk of type 2 diabetes and with a healthy diet. Our population-based study shows that the metabolite signature of increased PA includes multiple metabolic pathways and is associated with better adherence to a healthy lifestyle.

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Plasma Bile Acid Profile in Patients with and without Type 2 Diabetes

Cited by 40 publications

References 25 publications

Multi-Omics Comparison of the Spontaneous Diabetes Mellitus and Diet-Induced Prediabetic Macaque Models

Multi-Omics Comparison of the Spontaneous Diabetes Mellitus and Diet-Induced Prediabetic Macaque Models

Plasma Metabolic Signatures of Healthy Overweight Subjects Challenged With an Oral Glucose Tolerance Test

Metabolite Signature of Physical Activity and the Risk of Type 2 Diabetes in 7271 Men

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