|Lustgarten, Michael -|
|Price, Lori Lyn -|
|Phillips, Edward -|
|Fielding, Roger -|
Submitted to: PLoS One
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: November 11, 2013
Publication Date: December 31, 2013
Citation: Lustgarten, M.S., Price, L., Phillips, E.M., Fielding, R.A. 2013. Serum Glycine Is Associated with Regional Body Fat and Insulin Resistance in Functionally-Limited Older Adults. PLoS One. 8(12):e84034. DOI: 10.1371/journal.pone.0084034. Interpretive Summary: Identification of metabolites in blood that are associated with regional fat mass, and with insulin sensitivity may lead to targeted interventions designed to reduce fat mass and to reduce insulin resistance in older adults. Fasting levels of 181 total metabolites, including amino acids, fatty acids and acylcarnitines were measured and, statistical analysis identified the amino acid glycine to be negatively associated with thigh intermuscular and abdominal fat mass. In contrast, glycine was positively associated with insulin sensitivity, and, collectively these data suggest that future studies aimed at glycine repletion in older adults may be a viable strategy for reducing fat mass and for improving insulin sensitivity, in older adults.
Technical Abstract: Metabolic profiling may provide insight into biologic mechanisms related to age-related increases in regional adiposity and insulin resistance. The objectives of the current study were to characterize the association between mid-thigh intermuscular and subcutaneous adipose tissue (IMAT, SCAT, respectively) and, abdominal adiposity with the serum metabolite profile, to identify significant metabolites as further associated with the homeostasis model assessment of insulin resistance (HOMA-IR), and, to develop a HOMA-IR associated metabolite predictor set representative of regional adiposity, in 73 functionally-limited (short physical performance battery less than or equal to 10; SPPB) older adults (age range, 70-85 y).Fasting levels of 181 total metabolites, including amino acids, fatty acids and acylcarnitines were measured with use of an untargeted mass spectrometry-based metabolomic approach. Multivariable-adjusted linear regression was used in all analyses. Thirty-two, seven and one metabolite(s) were found to be associated with IMAT, abdominal adiposity and, SCAT, respectively, including the amino acid glycine, which was positively associated with SCAT and, negatively associated with both IMAT and abdominal adiposity. Glycine and four metabolites found to be significantly associated with regional adiposity were additionally associated with HOMA-IR. Separate stepwise regression models identified glycine as a HOMA-IR associated marker of both IMAT (model R**2'='0.51, p<0.0001) and abdominal adiposity (model R**2'='0.41, p<0.0001).Our findings for a positive association between glycine with SCAT but, a negative association between glycine with IMAT and abdominal adiposity supports the hypothesis that SCAT metabolic processes are different from that found in other fat depots. In addition, because of the significant associations found between glycine with HOMA-IR, IMAT, SCAT and abdominal adiposity, our results suggest glycine as a serum biomarker of both insulin sensitivity and regional fat mass in functionally-limited older adults.