Use of Metabolomic Profiling to Understand Variability in Adiposity Changes Following an Intentional Weight Loss Intervention in Older Adults

Abstract

Inter-individual response to dietary interventions remains a major challenge to successful weight loss among older adults. This study applied metabolomics technology to identify small molecule signatures associated with a loss of fat mass and overall weight in a cohort of older adults on a nutritionally complete, high-protein diet. A total of 102 unique metabolites were measured using liquid chromatography-mass spectrometry (LC-MS) for 38 adults aged 65-80 years randomized to dietary intervention and 36 controls. Metabolite values were analyzed in both baseline plasma samples and samples collected following the six-month dietary intervention to consider both metabolites that could predict the response to diet and those that changed in response to diet or weight loss.Eight metabolites changed over the intervention at a nominally significant level: D-pantothenic acid, L-methionine, nicotinate, aniline, melatonin, deoxycarnitine, 6-deoxy-L-galactose, and 10-hydroxydecanoate. Within the intervention group, there was broad variation in the achieved weight-loss and dual-energy x-ray absorptiometry (DXA)-defined changes in total fat and visceral adipose tissue (VAT) mass. Change in the VAT mass was significantly associated with the baseline abundance of α-aminoadipate (p = 0.0007) and an additional mass spectrometry peak that may represent D-fructose, myo-inositol, mannose, α-D-glucose, allose, D-galactose, D-tagatose, or L-sorbose (p = 0.0001). This hypothesis-generating study reflects the potential of metabolomic biomarkers for the development of personalized dietary interventions.

Keywords: aging; body composition; heterogeneity; metabolomics; weight loss.

Figure 1

Change in the weight and body composition. From baseline to six months, the percent change in total body weight, lean mass, fat mass, and visceral adipose tissue (VAT) mass in individuals randomized to the weight loss (orange; n = 38) and weight stable (teal; n = 36) groups.

Figure 2

Change in mean metabolite abundance in weight loss group. The distribution with mean and inter-quartile ranges are shown for eight metabolites with nominally significant p-values in Welch’s t-tests between baseline and the end of the six-month weight loss intervention.

Figure 3

Heatmap of differentially expressed metabolites between weight loss (WL) and weight stable (WS) groups at the end of the intervention. Based on metabolites with nominally significant (p < 0.05) Welch’s t-test results comparing the groups at the six month time point, this heatmap shows clustering of highly expressed (green) and lowly expressed (red) metabolites. The dendrogram at the top clusters individuals based on the similarity of their metabolite profiles with individuals in the WL group in orange and the WS group in teal.

Figure 4

Scatter plot of baseline metabolite abundance vs. change in visceral adipose tissue (VAT). (a) Abundance of α-aminoadipate at baseline in all individuals randomized to weight loss (WL) vs. VAT mass change in grams following the intervention. (b) Abundance of the indeterminate metabolite at baseline vs. VAT mass change for females in the WL group only.