Creatine kinase as a marker of obesity in a multi-ethnic population

Haan, Yentl C.; Oudman, Inge; Diemer, Frederieke S.; Karamat, Fares A.; Valkengoed, Irene G. M. van; Montfrans, Gert A. van; Brewster, Lizzy M.

doi:10.1016/j.mce.2016.11.022

Cited by 24 publications

(28 citation statements)

References 50 publications

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“…The intracellular creatine kinase (CK) system may be involved in the storage of fat and the development of obesity [ 97 – 99 ]. Besides, one cross-sectional study recently provided further evidence that CK may play a role in the pathophysiology of obesity and serve as a marker to identify individuals at risk for obesity [ 100 ]. (III) IL17C : Obesity, in some sense, is considered to be an inflammatory predisposition.…”

Section: Discussionmentioning

confidence: 99%

Weighted gene co-expression network analysis of expression data of monozygotic twins identifies specific modules and hub genes related to BMI

et al. 2017

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BackgroundThe therapeutic management of obesity is challenging, hence further elucidating the underlying mechanisms of obesity development and identifying new diagnostic biomarkers and therapeutic targets are urgent and necessary. Here, we performed differential gene expression analysis and weighted gene co-expression network analysis (WGCNA) to identify significant genes and specific modules related to BMI based on gene expression profile data of 7 discordant monozygotic twins.ResultsIn the differential gene expression analysis, it appeared that 32 differentially expressed genes (DEGs) were with a trend of up-regulation in twins with higher BMI when compared to their siblings. Categories of positive regulation of nitric-oxide synthase biosynthetic process, positive regulation of NF-kappa B import into nucleus, and peroxidase activity were significantly enriched within GO database and NF-kappa B signaling pathway within KEGG database. DEGs of NAMPT, TLR9, PTGS2, HBD, and PCSK1N might be associated with obesity. In the WGCNA, among the total 20 distinct co-expression modules identified, coral1 module (68 genes) had the strongest positive correlation with BMI (r = 0.56, P = 0.04) and disease status (r = 0.56, P = 0.04). Categories of positive regulation of phospholipase activity, high-density lipoprotein particle clearance, chylomicron remnant clearance, reverse cholesterol transport, intermediate-density lipoprotein particle, chylomicron, low-density lipoprotein particle, very-low-density lipoprotein particle, voltage-gated potassium channel complex, cholesterol transporter activity, and neuropeptide hormone activity were significantly enriched within GO database for this module. And alcoholism and cell adhesion molecules pathways were significantly enriched within KEGG database. Several hub genes, such as GAL, ASB9, NPPB, TBX2, IL17C, APOE, ABCG4, and APOC2 were also identified. The module eigengene of saddlebrown module (212 genes) was also significantly correlated with BMI (r = 0.56, P = 0.04), and hub genes of KCNN1 and AQP10 were differentially expressed.ConclusionWe identified significant genes and specific modules potentially related to BMI based on the gene expression profile data of monozygotic twins. The findings may help further elucidate the underlying mechanisms of obesity development and provide novel insights to research potential gene biomarkers and signaling pathways for obesity treatment. Further analysis and validation of the findings reported here are important and necessary when more sample size is acquired.Electronic supplementary materialThe online version of this article (10.1186/s12864-017-4257-6) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Weighted gene co-expression network analysis of expression data of monozygotic twins identifies specific modules and hub genes related to BMI

et al. 2017

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“…promoting energy metabolism in skeletal muscle, is associated with obesity [14], but the mechanisms are not clarified. High CK may have many causes [15], but it is not known whether CK is involved in obesity-related inflammation.…”

Section: Original Articlementioning

confidence: 99%

“…The phenomenon of crosstalk between myocytes, adipocytes and other tissue mediated by myocyte‐released factors (myokines) may interact with obesity . Creatine kinase (CK), an enzyme promoting energy metabolism in skeletal muscle, is associated with obesity , but the mechanisms are not clarified. High CK may have many causes , but it is not known whether CK is involved in obesity‐related inflammation.…”

Section: Introductionmentioning

confidence: 99%

Lean body mass and creatine kinase are associated with reduced inflammation in obesity

Bekkelund

Jorde

2017

Eur J Clin Investigation

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“…We have shown in a random, multi-ethnic population sample that plasma CK activity after rest, a surrogate measure of tissue CK, is a main predictor of blood pressure, with a crude increase in blood pressure of 14 mm Hg systolic per log CK increase [2]. Although plasma and tissue CK activity were found to be higher in men, persons of African ancestry and obese patients [2,7], the association was independent of sex, body mass index (BMI), or ethnicity, and has been replicated by others [2,4].…”

Section: Introductionmentioning

confidence: 97%

The acute effect of beta‐guanidinopropionic acid versus creatine or placebo in healthy men (ABC‐Trial): A randomized controlled first‐in‐human trial

Karamat

Horjus

Haan

et al. 2017

Brit J Clinical Pharma

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AimsIncreasing evidence indicates that the ATP‐generating enzyme creatine kinase (CK) is involved in hypertension. CK rapidly regenerates ATP from creatine phosphate and ADP. Recently, it has been shown that beta‐guanidinopropionic acid (GPA), a kidney‐synthesized creatine analogue and competitive CK inhibitor, reduced blood pressure in spontaneously hypertensive rats. To further develop the substance as a potential blood pressure‐lowering agent, we assessed the tolerability of a sub‐therapeutic GPA dose in healthy men.MethodsIn this active and placebo‐controlled, triple‐blind, single‐centre trial, we recruited 24 healthy men (18–50 years old, BMI 18.5–29.9 kg m−2) in the Netherlands. Participants were randomized (1:1:1) to one week daily oral administration of GPA 100 mg, creatine 5 g, or matching placebo. The primary outcome was the tolerability of GPA, in an intent‐to‐treat analysis.ResultsTwenty‐four randomized participants received the allocated intervention and 23 completed the study. One participant in the placebo arm dropped out for personal reasons. GPA was well tolerated, without serious or severe adverse events. No abnormalities were reported with GPA use in clinical safety parameters, including physical examination, laboratory studies, or 12‐Lead ECG. At day 8, mean plasma GPA was 213.88 (SE 0.07) in the GPA arm vs. 32.75 (0.00) nmol l−1 in the placebo arm, a mean difference of 181.13 (95% CI 26.53–335.72).ConclusionIn this first‐in‐human trial, low‐dose GPA was safe and well‐tolerated when used during 1 week in healthy men. Subsequent studies should focus on human pharmacokinetic and pharmacodynamic assessments with different doses.

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Creatine kinase as a marker of obesity in a multi-ethnic population

Cited by 24 publications

References 50 publications

Weighted gene co-expression network analysis of expression data of monozygotic twins identifies specific modules and hub genes related to BMI

Weighted gene co-expression network analysis of expression data of monozygotic twins identifies specific modules and hub genes related to BMI

Lean body mass and creatine kinase are associated with reduced inflammation in obesity

The acute effect of beta‐guanidinopropionic acid versus creatine or placebo in healthy men (ABC‐Trial): A randomized controlled first‐in‐human trial

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