Acquired obesity is associated with changes in the serum lipidomic profile independent of genetic effects--a monozygotic twin study

Abstract

Both genetic and environmental factors are involved in the etiology of obesity and the associated lipid disturbances. We determined whether acquired obesity is associated with changes in global serum lipid profiles independent of genetic factors in young adult monozygotic (MZ) twins. 14 healthy MZ pairs discordant for obesity (10 to 25 kg weight difference) and ten weight concordant control pairs aged 24-27 years were identified from a large population-based study. Insulin sensitivity was assessed by the euglycemic clamp technique, and body composition by DEXA (% body fat) and by MRI (subcutaneous and intra-abdominal fat). Global characterization of lipid molecular species in serum was performed by a lipidomics strategy using liquid chromatography coupled to mass spectrometry. Obesity, independent of genetic influences, was primarily related to increases in lysophosphatidylcholines, lipids found in proinflammatory and proatherogenic conditions and to decreases in ether phospholipids, which are known to have antioxidant properties. These lipid changes were associated with insulin resistance, a pathogonomic characteristic of acquired obesity in these young adult twins. Our results show that obesity, already in its early stages and independent of genetic influences, is associated with deleterious alterations in the lipid metabolism known to facilitate atherogenesis, inflammation and insulin resistance.

Figure 1

Two-dimensional representation of the lipid spectra for a selected illustrative sample obtained by reversed phase Ultra Performance Liquid Chromatography coupled to high resolution Mass Spectrometry (positive ion mode). Major lipid groups found in different parts of the spectra are marked. MZmine software , was utilized for visualization and spectral data processing.

Figure 2

Correlation maps for clinical variables. (A) Each individual considered separately (N = 48). (B) Twin pair normalized (N = 24).

Figure 3

Partial least squares discriminant analysis (PLS/DA) of lipidomics profiles for obesity discordant co-twins, utilizing only the 133 identified peaks and two classes (obese and non-obese co-twins) to build the model. Three latent variables were used (Q² = 47%). (A) PLS/DA score plot. Genders and twin-pair identifiers are marked for each sample, although this information was not used to build the model. (B) Fold changes for most important variables based on VIP analysis contributing to the PLS/DA model.

Figure 4

Twin-normalized Spearman rank correlations of (A) two most abundant lysophosphatidylcholine and (B) ether phospholipid species with clinical variables. ^* p<0.05, ^** p<0.01.

Figure 5

Correlation plots for selected sphingomyelin species and clinical variables in (A) individual twins, and (B) twin pairs.

Figure 6

Twin-normalized Spearman rank correlations of lipids with different fat depots: (A) BMI, (B) total body fat, (C) subcutaneous fat, and (D) intra-abdominal fat. ^* p<0.05, ^** p<0.01.

Figure 7

Twin-normalized Spearman rank correlations of lipids with (A) M-value and (B) insulin. ^* p<0.05, ^** p<0.01.

Figure 8

Correlations with classical lipid parameters using Spearman rank correlations across all individuals (N = 48). Only lipids with p<0.1 are reported for triglyceride and total cholesterol correlations. ^* p<0.05, ^** p<0.01, ***p<0.001.

Figure 9

Correlation of serum triglyceride measure with different triacylglycerol species as a function of (A) the amount, and (B) the number of fatty acid carbons.