Effects of smoking and smoking cessation on human serum metabolite profile: results from the KORA cohort study

Xu, Tao; Holzapfel, Christina; Dong, Xiao; Bader, Erik; Yu, Zhonghao; Prehn, Cornelia; Perstorfer, Katrin; Jaremek, Marta; Roemisch-Margl, Werner; Rathmann, Wolfgang; Li, Yixue; Wichmann, H‐Erich; Wallaschofski, Henri; Ladwig, Karl Heinz; Theis, Fabian J.; Suhre, Karsten; Adamski, Jerzy; Illig, Thomas; Peters, Annette; Wang-Sattler, Rui

doi:10.1186/1741-7015-11-60

Cited by 112 publications

(100 citation statements)

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“…The levels of metabolites depend on multiple modifiable factors, such as lifestyle and environment (9)(10)(11)(13)(14)(15)(16). We therefore considered a number of confounding effects, e.g., physiological parameters (age, sex, BMI, and systolic BP), lifestyle (physical activity, alcohol intake, and smoking), glucose levels (HbA 1c and fasting glucose), lipid levels (HDL-C and triglycerides), and medication usage (statins, b-blockers, ACE inhibitors, and ARBs).…”

Section: Discussionmentioning

confidence: 99%

“…Metabolomic studies have detected metabolite profile changes during the development of T2D (9)(10)(11)(12) and identified concentration differences caused by various physiological and environmental factors such as age (13), sex (14), smoking status (15), and alcohol consumption (16). Several metabolomic studies attempted to unravel the physiological effects of metformin (17)(18)(19)(20)(21).…”

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confidence: 99%

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Effects of Metformin on Metabolite Profiles and LDL Cholesterol in Patients With Type 2 Diabetes

et al. 2015

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OBJECTIVEMetformin is used as a first-line oral treatment for type 2 diabetes (T2D). However, the underlying mechanism is not fully understood. Here, we aimed to comprehensively investigate the pleiotropic effects of metformin. RESEARCH DESIGN AND METHODSWe analyzed both metabolomic and genomic data of the population-based KORA cohort. To evaluate the effect of metformin treatment on metabolite concentrations, we quantified 131 metabolites in fasting serum samples and used multivariable linear regression models in three independent cross-sectional studies (n = 151 patients with T2D treated with metformin [mt-T2D]). Additionally, we used linear mixed-effect models to study the longitudinal KORA samples (n = 912) and performed mediation analyses to investigate the effects of metformin intake on blood lipid profiles. We combined genotyping data with the identified metforminassociated metabolites in KORA individuals (n = 1,809) and explored the underlying pathways. RESULTSWe found significantly lower (P < 5.0E-06) concentrations of three metabolites (acyl-alkyl phosphatidylcholines [PCs]) when comparing mt-T2D with four control groups who were not using glucose-lowering oral medication. These findings were controlled for conventional risk factors of T2D and replicated in two independent studies. Furthermore, we observed that the levels of these metabolites decreased significantly in patients after they started metformin treatment during 7 years' follow-up. The reduction of these metabolites was also associated with a lowered blood level of LDL cholesterol (LDL-C). Variations of these three metabolites were significantly associated with 17 genes (including FADS1 and FADS2) and controlled by AMPK, a metformin target. CONCLUSIONSOur results indicate that metformin intake activates AMPK and consequently suppresses FADS, which leads to reduced levels of the three acyl-alkyl PCs and LDL-C. Our findings suggest potential beneficial effects of metformin in the prevention of cardiovascular disease.Type 2 diabetes (T2D) is a chronic disease with diminished response to insulin and relative insulin deficiency (1). Patients with T2D mostly take metformin as first-line oral treatment to lower their glucose levels and to improve insulin sensitivity (2). Despite metformin's use as an antihyperglycemic agent for more than 50 years, its

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

Effects of Metformin on Metabolite Profiles and LDL Cholesterol in Patients With Type 2 Diabetes

et al. 2015

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“…This suggests that lipid metabolism is abnormal in schizophrenic patients before the commencement of antipsychotic drug treatment. It is well-known that smoking alters serum lipid profiles, as characterized by increased total cholesterol (TC), triglycerides (TG), ApoB/ApoA1 ratio, and low-density lipoprotein cholesterol (LDL-c), along with decreased high-density lipoprotein cholesterol (HDL-c) [14][15][16]. However, the mechanisms by which smoking changes serum lipid and lipoprotein levels are still unknown.…”

Section: And Thomas R Kostenmentioning

confidence: 99%

“…Unexpectedly, we found no significant differences in the lipid profiles of smokers versus non-smokers. In the general population, smoking is associated with abnormal profiles, such as elevated TC, TG, LDL-c, and ApoB, and reduced HDL-c and ApoA1 [14][15][16], suggesting that smoking has potentially long-term atherogenic effects on lipid metabolism. The biological mechanisms linking smoking and atherogenesis are complex, but a presumed linkage is that nicotine stimulates the sympathetic adrenal system to secrete catecholamines [26] These catecholamines then increase lipolysis and the concentration of plasma free fatty acids, which in turn increases the synthesis of hepatic TG and VLDL-c in the blood stream [17,18].…”

Section: Symptoms and Lipid Profiles In Smokers Versus Non-smokersmentioning

confidence: 99%

Smoking and Serum Lipid Profiles in Schizophrenia

Tan

et al. 2016

Neurosci. Bull.

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Schizophrenia is associated with a high prevalence of cigarette-smoking and abnormal lipid profiles. The purpose of this study was to determine whether the profiles differ between schizophrenic smokers and non-smokers and whether the lipid profiles are related to psychopathological symptoms. Serum lipid profiles were measured in 130 male inpatients with DSM-IV-defined schizophrenia: 104 smokers and 26 non-smokers. Symptoms were assessed using the Positive and Negative Syndrome Scale (PANSS). Our results showed that positive PANSS symptoms were fewer in smokers than in non-smokers, while the negative symptoms were fewer in those who smoked more cigarettes. Total protein and globulin levels were significantly lower in the smokers than in the non-smokers. However, there was no significant difference in total cholesterol, triglycerides, high-density lipoprotein cholesterol (HDL-c), low-density lipoprotein cholesterol, apolipoprotein A1, or apolipoprotein B between the smokers and non-smokers. However, the PANSS positive subscale had a significant negative correlation with the HDL-c levels (a protective factor) in the smokers but not in the non-smokers. Our findings suggest that schizophrenic patients who smoke have fewer psychotic symptoms, but contrary to expectation, smoking does not alter lipid profile levels.

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“…Additionally, obesity and smoking were associated with alterations in amino acids metabolites. [6][7][8][9] All these studies compared individuals with or without a determined risk factor at a given time point, crosssectionally. However, the long-term effects of these risk factors on the human metabolism are to date unknown, that is, are they associated with changes in metabolite concentrations?…”

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confidence: 99%

Cardiovascular Risk Factors Associated With Blood Metabolite Concentrations and Their Alterations During a 4-Year Period in a Population-Based Cohort

Lacruz

Kluttig

Tiller

et al. 2016

Circ Cardiovasc Genet

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C ardiovascular disease (CVD) is a leading cause of mortality, accounting for >30% of deaths worldwide.1 There are several modifiable (ie, obesity, smoking, alcohol, physical activity, and diet) and also unmodifiable risk factors (ie, sex and age) associated with CVD; however, the pathophysiological mechanisms of the association between risk factors and disease are not yet fully understood. Clinical Perspective on p 494Metabolomics aims to quantify small molecules present in a biological system at a specific time point. This snapshot provides an indication of the current metabolic state of the whole organism at a given stage of life. Differences in metabolic profiles can be because of pathological stimuli, environmental impact, or normal physiological variations. Several studies have shown that metabolomics can identify distinct metabolic patterns in individuals affected by pathological conditions, that is, atherosclerosis, diabetes mellitus, or cardiovascular disorders. 2-5The effects of several classic modifiable CVD risk factors on metabolism have already been studied in different population-based cohorts. In particular, alcohol intake, obesity, diet patterns, and smoking were shown to be associated Background-The effects of lifestyle risk factors considered collectively on the human metabolism are to date unknown.We aim to investigate the association of these risk factors with metabolites and their changes during 4 years. Methods and Results-One hundred and sixty-three metabolites were measured in serum samples with the AbsoluteIDQ kit p150 (Biocrates) following a targeted metabolomics approach, in a population-based cohort of 1030 individuals, aged 45 to 83 years at baseline. We evaluated associations between metabolite concentrations (28 acylcarnitines, 14 amino acids, 9 lysophosphocholines, 72 phosphocholines, 10 sphingomyelins and sum of hexoses) and 5 lifestyle risk factors (body mass index [BMI], alcohol consumption, smoking, diet, and exercise). Multilevel or simple linear regression modeling adjusted for relevant covariates was used for the evaluation of cross-sectional or longitudinal associations, respectively; multiple testing correction was based on false discovery rate. BMI, alcohol consumption, and smoking were associated with lipid metabolism (reduced lyso-and acyl-alkyl-phosphatidylcholines and increased diacylphosphatidylcholines concentrations). Smoking showed positive associations with acylcarnitines, and BMI correlated inversely with nonessential amino acids. Fewer metabolites showed relative changes that were associated with baseline risk factors: increases in 5 different acyl-alkyl phosphatidylcholines were associated with lower alcohol consumption and BMI and with a healthier diet. Increased levels of tyrosine were associated with BMI. Sex-specific effects of smoking and BMI were found specifically related to acylcarnitine metabolism: in women higher BMI and in men more pack-years were associated with increases in acylcarnitines. with alterations in lipid metabolism. Additionally, obe...

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Effects of smoking and smoking cessation on human serum metabolite profile: results from the KORA cohort study

Cited by 112 publications

References 50 publications

Effects of Metformin on Metabolite Profiles and LDL Cholesterol in Patients With Type 2 Diabetes

Effects of Metformin on Metabolite Profiles and LDL Cholesterol in Patients With Type 2 Diabetes

Smoking and Serum Lipid Profiles in Schizophrenia

Cardiovascular Risk Factors Associated With Blood Metabolite Concentrations and Their Alterations During a 4-Year Period in a Population-Based Cohort

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