Gut microbiota metabolites, amino acid metabolites and improvements in insulin sensitivity and glucose metabolism: the POUNDS Lost trial
Yoriko Heianza, Dianjianyi Sun, Xiang Li, Joseph A DiDonato, George A Bray, Frank M Sacks, Lu Qi, Yoriko Heianza, Dianjianyi Sun, Xiang Li, Joseph A DiDonato, George A Bray, Frank M Sacks, Lu Qi
Abstract
Objective: Alterations in gut microbiota have been linked to host insulin resistance, diabetes and impaired amino acid metabolism. We investigated whether changes in gut microbiota-dependent metabolite of trimethylamine N-oxide (TMAO) and its nutrient precursors (choline and L-carnitine) were associated with improvements in glucose metabolism and diabetes-related amino acids in a weight-loss diet intervention.
Design: We included 504 overweight and obese adults who were randomly assigned to one of four energy-reduced diets varying in macronutrient intake. The 6-month changes (Δ) in TMAO, choline and L-carnitine levels after the intervention were calculated.
Results: Greater decreases in choline and L-carnitine were significantly (p<0.05) associated with greater improvements in fasting insulin concentrations and homeostasis model assessment of insulin resistance (HOMA-IR) at 6 months. The reduction of choline was significantly related to 2-year improvements in glucose and insulin resistance. We found significant linkages between dietary fat intake and ΔTMAO for changes in fasting glucose, insulin and HOMA-IR (pinteraction <0.05); a greater increase in TMAO was related to lesser improvements in the outcomes among participants who consumed a high-fat diet. In addition, ΔL-carnitine and Δcholine were significantly related to changes in amino acids (including branched-chain and aromatic amino acids). Interestingly, the associations of ΔTMAO, Δcholine and ΔL-carnitine with diabetes-related traits were independent of the changes in amino acids.
Conclusion: Our findings underscore the importance of changes in TMAO, choline and L-carnitine in improving insulin sensitivity during a weight-loss intervention for obese patients. Dietary fat intake may modify the associations of TMAO with insulin sensitivity and glucose metabolism.
Trial registration number: NCT00072995.
Keywords: amino acids; clinical trials; glucose metabolism; nutrition.
Conflict of interest statement
Competing interests: None declared.
© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2019. All rights reserved. No commercial use is permitted unless otherwise expressly granted.
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Source: PubMed