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

Yoriko Heianza, Tao Zhou, Hua He, Joseph A DiDonato, George A Bray, Frank M Sacks, Lu Qi, Yoriko Heianza, Tao Zhou, Hua He, Joseph A DiDonato, George A Bray, Frank M Sacks, Lu Qi

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.

Conflict of interest statement

Conflicts of Interest: The authors declare no conflict of interest associated with this publication.

© 2021. The Author(s), under exclusive licence to Springer Nature Limited.

Figures

Figure 1:
Figure 1:
Two-year changes in cholesterol in lipoproteins containing apolipoprotein (apo) C-III according to tertile (T) categories of L-carnitine changes. Data are mean and SE in the general linear model after adjusting for age, sex, ethnicity, diet groups, use of lipid-lowering medication, baseline BMI, baseline levels of the respective outcome, and baseline L-carnitine. For Δ L-carnitine, median (25th, 75th) values were T1: −5.0 (–7.5, −3.4) μM, T2: 0.2 (–0.9, 1.1) μM, and T3: 4.7 (3.2, 6.7) μM, respectively.
Figure 2:
Figure 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. Pinteraction between dietary fat and TMAO changes were for each outcome. Data are mean and SE in the general linear model after adjusting for age, sex, ethnicity, diet groups, use of lipid-lowering medication, baseline BMI, baseline levels of the respective outcome, and baseline TMAO. For ΔTMAO, median (25th, 75th) values were T1: −2.0 (–3.5, −1.2) μM, T2: 0 (–0.3, 0.3) μM, and T3: 1.9 (1.3, 4.0) μM, respectively among the total participants.

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