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
<p><strong>Aims/Hypothesis:</strong><br /> 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 associati...
| Main Authors: | , , , , , |
|---|---|
| Format: | Journal article |
| Language: | English |
| Published: |
Springer
2019
|
| _version_ | 1797060571091173376 |
|---|---|
| author | Vasan, SK Noordam, R Gowri, MS Neville, MJ Karpe, F Christodoulides, C |
| author_facet | Vasan, SK Noordam, R Gowri, MS Neville, MJ Karpe, F Christodoulides, C |
| author_sort | Vasan, SK |
| collection | OXFORD |
| description | <p><strong>Aims/Hypothesis:</strong><br />
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.</p><br />
<p><strong>Methods:</strong><br />
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.</p><br />
<p><strong>Results:</strong><br />
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.</p><br />
<p><strong>Conclusions/Interpretation:</strong><br />
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.</p> |
| first_indexed | 2024-03-06T20:18:56Z |
| format | Journal article |
| id | oxford-uuid:2d21d152-442f-4b71-b244-42358a61868c |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T20:18:56Z |
| publishDate | 2019 |
| publisher | Springer |
| record_format | dspace |
| spelling | oxford-uuid:2d21d152-442f-4b71-b244-42358a61868c2022-03-26T12:41:02ZThe 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 studyJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:2d21d152-442f-4b71-b244-42358a61868cEnglishSymplectic Elements at OxfordSpringer2019Vasan, SKNoordam, RGowri, MSNeville, MJKarpe, FChristodoulides, C<p><strong>Aims/Hypothesis:</strong><br /> 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.</p><br /> <p><strong>Methods:</strong><br /> 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.</p><br /> <p><strong>Results:</strong><br /> 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.</p><br /> <p><strong>Conclusions/Interpretation:</strong><br /> 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.</p> |
| spellingShingle | Vasan, SK Noordam, R Gowri, MS Neville, MJ Karpe, F Christodoulides, C 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 |
| title | 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 |
| title_full | 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 |
| title_fullStr | 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 |
| title_full_unstemmed | 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 |
| title_short | 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 |
| title_sort | 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 |
| work_keys_str_mv | AT vasansk theproposedsystemicthermogenicmetabolitessuccinateand1213dihomeareinverselyassociatedwithadiposityandrelatedmetabolictraitsevidencefromalargehumancrosssectionalstudy AT noordamr theproposedsystemicthermogenicmetabolitessuccinateand1213dihomeareinverselyassociatedwithadiposityandrelatedmetabolictraitsevidencefromalargehumancrosssectionalstudy AT gowrims theproposedsystemicthermogenicmetabolitessuccinateand1213dihomeareinverselyassociatedwithadiposityandrelatedmetabolictraitsevidencefromalargehumancrosssectionalstudy AT nevillemj theproposedsystemicthermogenicmetabolitessuccinateand1213dihomeareinverselyassociatedwithadiposityandrelatedmetabolictraitsevidencefromalargehumancrosssectionalstudy AT karpef theproposedsystemicthermogenicmetabolitessuccinateand1213dihomeareinverselyassociatedwithadiposityandrelatedmetabolictraitsevidencefromalargehumancrosssectionalstudy AT christodoulidesc theproposedsystemicthermogenicmetabolitessuccinateand1213dihomeareinverselyassociatedwithadiposityandrelatedmetabolictraitsevidencefromalargehumancrosssectionalstudy AT vasansk proposedsystemicthermogenicmetabolitessuccinateand1213dihomeareinverselyassociatedwithadiposityandrelatedmetabolictraitsevidencefromalargehumancrosssectionalstudy AT noordamr proposedsystemicthermogenicmetabolitessuccinateand1213dihomeareinverselyassociatedwithadiposityandrelatedmetabolictraitsevidencefromalargehumancrosssectionalstudy AT gowrims proposedsystemicthermogenicmetabolitessuccinateand1213dihomeareinverselyassociatedwithadiposityandrelatedmetabolictraitsevidencefromalargehumancrosssectionalstudy AT nevillemj proposedsystemicthermogenicmetabolitessuccinateand1213dihomeareinverselyassociatedwithadiposityandrelatedmetabolictraitsevidencefromalargehumancrosssectionalstudy AT karpef proposedsystemicthermogenicmetabolitessuccinateand1213dihomeareinverselyassociatedwithadiposityandrelatedmetabolictraitsevidencefromalargehumancrosssectionalstudy AT christodoulidesc proposedsystemicthermogenicmetabolitessuccinateand1213dihomeareinverselyassociatedwithadiposityandrelatedmetabolictraitsevidencefromalargehumancrosssectionalstudy |