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EPIDEMIOLOGY AND POPULATION HEALTH

Changes in gut-microbiota-related metabolites and long-term improvements in lipoprotein subspecies in overweight and obese adults: the POUNDS lost trial

International Journal of Obesity volume 45, pages 2600–2607 (2021)Cite this article

Subjects

Abstract

Background/objectives

Alterations in gut microbiota have been linked to obesity and impaired lipid metabolism. Lipoproteins are heterogeneous, and lipoprotein subspecies containing apolipoprotein C-III (apoCIII) have adverse associations with obesity and related cardiometabolic abnormalities. We investigated associations of weight-loss diet-induced decreases in atherogenic gut-microbial metabolites, trimethylamine N-oxide (TMAO) and L-carnitine, with improvements in atherogenic lipoproteins containing apoCIII among patients with obesity.

Subjects/methods

This study included overweight and obese adults who participated in a 2-year weight-loss dietary intervention, the POUNDS Lost trial. Blood levels of TMAO and L-carnitine were measured at baseline and 6 months after the intervention; 6-month changes in the metabolites were calculated. We evaluated 2-year changes in lipid profiles (n = 395) and cholesterol [Chol] in lipoprotein (very-low-density lipoprotein (VLDL), low-density lipoprotein (LDL), and high-density lipoprotein (HDL)) subfractions defined by the presence or absence of apoCIII (n = 277).

Results

The initial (6-month) decrease in L-carnitine was significantly associated with long-term (2-year) reductions in non-HDL-Chol and LDL-Chol (p < 0.05). Also, the decrease in L-carnitine was significantly related to decreases in Chol in LDL with apoCIII (p = 0.034) and Chol in [LDL + VLDL] with apoCIII (p = 0.018). We found significant interactions between dietary fat and TMAO on changes in LDL-Chol (Pinteraction = 0.013) and Chol in [LDL + VLDL] with apoCIII (Pinteraction = 0.0048); a greater increase in TMAO was related to lesser improvements in the lipoprotein outcomes if participants consumed a high-fat compared to a low-fat diet.

Conclusions

Changes in TMAO and L-carnitine induced by weight-loss diets were associated with long-term improvements in atherogenic lipoproteins containing apoCIII, implicating that these metabolic changes might be predictive of an individual’s response to the dietary treatment to modify the unfavorable lipid profiles in obese patients. Dietary fat intake might modify associations of TMAO changes with long-term improvements of atherogenic cholesterol metabolism in overweight and obese adults.

ClinicalTrials.gov Identifier

NCT00072995

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Fig. 1: Two-year changes in cholesterol in lipoproteins containing apolipoprotein (apo) C-III according to tertile (T) categories of L-carnitine changes.
Fig. 2: Changes in LDL cholesterol and cholesterol in LDL and VLDL containing apolipoprotein C-III (apoCIII) at 2 years according to tertile (T) categories of TMAO changes in low-fat or high-fat diet group.

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Data availability

Dataset analyzed during the present study is available from the corresponding author on reasonable request. The data supporting the conclusions of this work are included in the manuscript.

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Acknowledgements

The authors thank all of the participants in the study for their dedication and contribution to the research. The authors also thank the Prevention Research Laboratory and Laboratory Diagnostic Core, Cleveland Clinic for the measurements of TMAO and L-carnitine.

Funding

The study is supported by National Institutes of Health (NIH) grants from the National Heart, Lung, and Blood Institute (HL071981, HL034594, HL126024), the National Institute of Diabetes and Digestive and Kidney Diseases (DK091718, DK100383, DK115679), an NIH shared instrumentation grant (S10OD016346), the Boston Obesity Nutrition Research Center (DK46200), and United States–Israel Binational Science Foundation Grant 2011036. LQ was a recipient of the American Heart Association (AHA) Scientist Development Award (0730094N). YH was a recipient of a Grant-in-Aid for Scientific Research (14J30007), a Postdoctoral Fellowship for Research Abroad from the Japan Society for the Promotion of Science, and AHA postdoctoral fellowship award (19POST34380035). This study is also supported by the Tulane University Research Centers of Excellence Awards. The sponsors had no role in the design or conduct of the study.

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Authors and Affiliations

  1. Department of Epidemiology, School of Public Health and Tropical Medicine, Tulane University, New Orleans, LA, USA

    Yoriko Heianza, Tao Zhou, Hua He & Lu Qi

  2. Center for Microbiome and Human Health, Cleveland Clinic, Cleveland, OH, USA

    Joseph A. DiDonato

  3. Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, LA, USA

    George A. Bray

  4. Department of Nutrition, Harvard T.H, Chan School of Public Health, Boston, MA, USA

    Frank M. Sacks & Lu Qi

Authors
  1. Yoriko Heianza
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  2. Tao Zhou
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  3. Hua He
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  4. Joseph A. DiDonato
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  5. George A. Bray
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Contributions

YH contributed to the study concept and design, analysis and interpretation of data, drafting and revising the manuscript, statistical analysis, and study supervision. TZ and HH contributed analysis and interpretation of data, and revising the manuscript. JAD contributed to mesurements, interpretation of data, and revising the manuscript. GB and FS contributed to acquisition of data, interpretation of data, and drafting and revising the manuscript. LQ contributed to the study concept and design, acquisition of data, analysis and interpretation of data, drafting and revising the manuscript, statistical analysis, and funding and study supervision. All authors were involved in the writing of the manuscript and approved the final version of this article. LQ and YH had full access to all of the data in the study and took responsibility for the integrity of the data and the accuracy of the data analysis.

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Correspondence to Yoriko Heianza or Lu Qi.

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Heianza, Y., Zhou, T., He, H. et al. Changes in gut-microbiota-related metabolites and long-term improvements in lipoprotein subspecies in overweight and obese adults: the POUNDS lost trial. Int J Obes 45, 2600–2607 (2021). https://doi.org/10.1038/s41366-021-00939-7

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