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Changes in Gut Microbiota-Related Metabolites and Long-term Successful Weight Loss in Response to Weight-Loss Diets: The POUNDS Lost Trial.
Heianza, Y, Sun, D, Smith, SR, Bray, GA, Sacks, FM, Qi, L
Diabetes care. 2018;41(3):413-419
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Evidence has demonstrated that weight loss contributes to lowering the risk of developing type 2 diabetes among obese patients. The aim of this study was to examine whether diet-induced metabolites were associated with improvements in adiposity and metabolism during a weight-loss diet intervention in 510 overweight and obese individuals. Participants were randomly assigned to one of four diets with varying macronutrient composition to adhere to for six months. Blood samples and anthropometric data were taken at baseline and 6 months to monitor changes. This study found that overweight and obese individuals with reduced choline or L-carnitine levels achieved greater improvements of adiposity and energy metabolism. Based on these results, the authors conclude that metabolites are predictive of patient responsiveness to dietary interventions, and suggest further studies evaluate these effects in the pre-diabetic obese population.
Abstract
OBJECTIVE Adiposity and the gut microbiota are both related to the risk of type 2 diabetes. We aimed to comprehensively examine how changes induced by a weight-loss diet intervention in gut microbiota-related metabolites, such as trimethylamine N-oxide (TMAO) and its precursors (choline and l-carnitine), were associated with improvements in adiposity and regional fat deposition. RESEARCH DESIGN AND METHODS This study included 510 overweight and obese individuals who were randomly assigned one of four diets varying in macronutrient intake. We examined associations of 6-month changes in blood metabolites (TMAO, choline, and l-carnitine) with improvements in body weight (BW), waist circumference (WC), body fat composition, fat distribution, and resting energy expenditure (REE). RESULTS Individuals with a greater reduction of choline (P < 0.0001) and l-carnitine (P < 0.01) rather than TMAO showed significant losses of BW and WC at 6 months. The reduction of choline was significantly predictive of decreases in body fat composition, fat distribution, and REE. Results of sensitivity analysis showed that the baseline diabetes risk status, such as the presence of hyperglycemia (31% of the total participants) and fasting glucose levels, did not modify the associations. Early changes in choline and l-carnitine were significantly predictive of weight loss over 2 years (P < 0.05 for all). Individuals with increases in choline or l-carnitine were 2.35-times (95% CI 1.38, 4.00) or 1.77-times (1.06, 2.95) more likely to fail to lose weight (-5% or more loss) at 2 years. CONCLUSIONS Overweight and obese individuals who showed decreases in circulating choline or l-carnitine levels achieved greater improvements of adiposity and energy metabolism by eating a low-calorie weight-loss diet, suggesting that such metabolites are predictive of individuals' response to the treatment. Further investigations are necessary to confirm our findings, particularly in a population with prediabetes that is more representative of the U.S. population with obesity.
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Starch Digestion-Related Amylase Genetic Variant Affects 2-Year Changes in Adiposity in Response to Weight-Loss Diets: The POUNDS Lost Trial.
Heianza, Y, Sun, D, Wang, T, Huang, T, Bray, GA, Sacks, FM, Qi, L
Diabetes. 2017;66(9):2416-2423
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Salivary and pancreatic amylases are responsible for the digestion of starchy foods. Specific genes that encode these amylases control both the activity and amount produced. While increasing evidence suggests the AMY1 gene is associated with obesity, existing results have not been conclusive. The aim of this study was to investigate whether genetic variations involved in starch metabolism are associated with long-term changes in adiposity among 692 overweight and obese individuals. Participants were randomly assigned to diets varying in macronutrient content for two years. Anthropometric measurements were recorded at baseline and every six months and blood samples were taken at baseline, 6 and 24 months. This study found the AMY1-AMY2 rs11185098 genotype to be associated with higher amylase activity, as well as reductions in body weight and waist circumference. Based on these results, the authors conclude overweight and obese individuals carrying this genotype may experience greater loss of adiposity during weight-loss interventions.
Abstract
Salivary and pancreatic amylases (encoded by AMY1 and AMY2 genes, respectively) are responsible for digesting starchy foods. AMY1 and AMY2 show copy number variations that affect differences in amylase amount and activity, and AMY1 copies have been associated with adiposity. We investigated whether genetic variants determining amylase gene copies are associated with 2-year changes in adiposity among 692 overweight and obese individuals who were randomly assigned to diets varying in macronutrient content. We found that changes in body weight (BW) and waist circumference (WC) were significantly different according to the AMY1-AMY2 rs11185098 genotype. Individuals carrying the A allele (indicating higher amylase amount and activity) showed a greater reduction in BW and WC at 6, 12, 18, and 24 months than those without the A allele (P < 0.05 for all). The association was stronger for long-term changes compared with short-term changes of these outcomes. The genetic effects on these outcomes did not significantly differ across diet groups. In conclusion, the genetic variant determining starch metabolism influences the response to weight-loss dietary intervention. Overweight and obese individuals carrying the AMY1-AMY2 rs11185098 genotype associated with higher amylase activity may have greater loss of adiposity during low-calorie diet interventions.