Abstract 47: Changes in Gut-microbial Metabolite L-carnitine and Improvements in Atherogenic Lipoprotein Metabolism in Overweight and Obese Individuals: The POUNDS Lost Trial

Abstract

Introduction: Atherogenic lipoproteins, apolipoproteins (apo), and lipoprotein subspecies with apo CIII are risk factors for cardiovascular disease (CVD). A gut-microbiota related metabolite L-carnitine has been found to promote atherosclerosis and may be related to an increased risk of CVD. Associations of L-carnitine with atherogenic lipid metabolism have not been clarified. Hypothesis: We tested a hypothesis that diet-induced changes in L-carnitine might contribute to improving atherogenic lipid profiles among overweight and obese adults. Methods: A total of 510 participants had data on blood levels of L-carnitine and lipid markers in a 2-year weight-loss dietary intervention trial. We measured 35 specialized lipid profiles including apo B and cholesterol concentrations in lipoprotein fractions (defined by the presence or absence of apo C-III) in 279 participants. Results: Higher baseline L-carnitine levels were significantly associated with elevated concentrations of triglycerides (p=0.0048) and lower HDL cholesterol (p=0.01) levels. Higher L-carnitine levels were also associated with elevated concentrations of cholesterol and apo B in lipoprotein fractions with apo CIII, such as cholesterol in VLDL with apo CIII (p=0.02), cholesterol in LDL with apo CIII (p=0.0056), apo B in HDL with apo CIII (p=0.01), apo B in VLDL with apo CIII (p=0.0008), and apo B in LDL with apo CIII (p=0.0038). We found that people with 6-month decreases in L-carnitine after the dietary intervention (median change: -3.4 μM) had significantly reduced LDL cholesterol levels over 2 years (p < 0.05; Fig, A). Also, people with greater increases in L-carnitine (median change: 3.2 μM) showed 2-year increases in cholesterol in VLDL with apo CIII or in LDL with apo CIII (p < 0.05 for both) (Fig, B). Conclusions: Diet-induced decreases in gut-microbiota-related metabolite L-carnitine may have significant influences on long-term improvements in atherogenic lipid profiles among obese patients in a dietary intervention.