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
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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: ) 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.
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In humans, circulating 12,13-diHOME is inversely associated with adipose tissue mass, fasting insulin and triacylglycerol.
“In humans, circulating levels of 12,13-diHOME are inversely associated with adipose tissue mass, fasting blood levels of insulin and blood levels of triacylglycerol92.”
From Exerkines in health, resilience and disease (2022) · cites this paper as [92]
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References 36 · Cited by 76
- Authors
- Vasan, S. K., Noordam, R., Gowri, M. S., Neville, M. J., Karpe, F., & Christodoulides, C.
- Affiliations
- Churchill Hospital (GB)
- Leiden University Medical Center (NL)
- Christian Medical College, Vellore (IN)
- Corresponding author
- Karpe, Fredrik
- Christodoulides, Constantinos
- ORCID
- Venue
- Diabetologia
- Published
- 2019-07-15
- Volume
- 62
- Issue
- 11
- Pages
- 2079-2087
- ISSN
- 0012-186X (ISSN-L)
- 1432-0428
- PMC
- PMC6805813
- OpenAlex
- W2960395343
- Cited by
- 76
- References
- 36
- Citations by year
- 2026: 9 · 2025: 9 · 2024: 14 · 2023: 19 · 2022: 6 · 2021: 11 · 2020: 8
- FWCI
- 4.29
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- Diabetologia (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- ePrints Soton (University of Southampton) (acceptedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Leiden Repository (Leiden University) (submittedVersion)
- Funders
- British Heart Foundation (RG/17/1/32663)
- National Institute for Health Research, Oxford Biomedical Research Centre (Obesity and Nutrition theme)
- Topics
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Disease and Adiposity
- Keywords
- succinic acid, 12,13-diHOME, adiposity, brown adipose tissue thermogenesis, fat mass, fasting insulin, triglycerides, body composition, energy metabolism, Mendelian randomization
- MeSH terms
- Adult, Adipose Tissue, Brown, Cross-Sectional Studies, Energy Metabolism, Female, Humans, Insulin Resistance, Male, Middle Aged, Obesity, Oleic Acids, Body Mass Index, Adipocytes, Succinic Acid, Thermogenesis, Adiposity, Mendelian Randomization Analysis
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