The proposed systemic thermogenic metabolites succinate and 12,13-diHOME are inversely associated with adiposity and related metabolic traits: evidence from a large human cross-sectional study

53Citations
Citations of this article
49Readers
Mendeley users who have this article in their library.

This article is free to access.

Abstract

Aims/hypothesis: Circulating succinate and 12,13-dihydroxy-9Z-octadecenoic acid (12,13-diHOME) were recently shown to promote brown adipocyte thermogenesis and protect against metabolic disorders in rodents. This study aimed to evaluate the associations between plasma levels of these metabolites and adiposity and metabolic profile in humans. Methods: Fasting plasma succinate and 12,13-diHOME levels were quantified using ultra HPLC-tandem MS in 2248 individuals (50% female, mean age 41.3 ± 5.9 years, mean BMI 26.1 ± 4.6 kg/m2) in addition to fasting plasma biochemistry. Total and regional adiposity were assessed with dual-energy x-ray absorptiometry. An age- and sex-adjusted linear regression model was used to determine the associations between succinate and 12,13-diHOME levels and body composition and metabolic profile. Two-sample Mendelian randomisation was used to assess the associations between genetically determined BMI and metabolic traits with circulating plasma succinate and 12,13-diHOME. Results: A one-SD higher plasma succinate and 12,13-diHOME concentration was associated with a 0.15 SD (95% CI 0.28, 0.03) and 0.08 SD (0.15, 0.01) lower total fat mass respectively. Additionally, a one-SD higher plasma 12,13-diHOME level was associated with a 0.09 SD (0.16, 0.02) lower fasting plasma insulin and 0.10 SD (0.17, 0.04) lower plasma triacylglycerol. In Mendelian randomisation analyses, genetically determined higher BMI, fasting hyperinsulinaemia and elevated lipid levels were not associated with changes in either plasma succinate or plasma 12,13-diHOME concentrations. No indications of bias due to directional pleiotropy were detected in the Mendelian randomisation analyses. Conclusions/interpretation: Our findings tentatively suggest that plasma succinate and 12,13-diHOME may play a role in the regulation of energy metabolism and brown adipose tissue activation in humans. Further studies encompassing direct assessment of brown adipose tissue activity and dietary supplementation are necessary to investigate the potential beneficial effects of these metabolites on systemic metabolism.

References Powered by Scopus

Mendelian randomization with invalid instruments: Effect estimation and bias detection through Egger regression

5718Citations
N/AReaders
Get full text

Consistent Estimation in Mendelian Randomization with Some Invalid Instruments Using a Weighted Median Estimator

5236Citations
N/AReaders
Get full text

The MR-base platform supports systematic causal inference across the human phenome

4381Citations
N/AReaders
Get full text

Cited by Powered by Scopus

Exerkines in health, resilience and disease

421Citations
N/AReaders
Get full text

Lipid and glucose metabolism in white adipocytes: pathways, dysfunction and therapeutics

322Citations
N/AReaders
Get full text

Cytochrome P450-derived linoleic acid metabolites EpOMEs and DiHOMEs: a review of recent studies

146Citations
N/AReaders
Get full text

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Cite

CITATION STYLE

APA

Vasan, S. K., Noordam, R., Gowri, M. S., Neville, M. J., Karpe, F., & Christodoulides, C. (2019). The proposed systemic thermogenic metabolites succinate and 12,13-diHOME are inversely associated with adiposity and related metabolic traits: evidence from a large human cross-sectional study. Diabetologia, 62(11), 2079–2087. https://doi.org/10.1007/s00125-019-4947-5

Readers' Seniority

Tooltip

PhD / Post grad / Masters / Doc 15

68%

Researcher 4

18%

Professor / Associate Prof. 2

9%

Lecturer / Post doc 1

5%

Readers' Discipline

Tooltip

Biochemistry, Genetics and Molecular Bi... 11

48%

Medicine and Dentistry 6

26%

Agricultural and Biological Sciences 4

17%

Pharmacology, Toxicology and Pharmaceut... 2

9%

Save time finding and organizing research with Mendeley

Sign up for free