Research Article: Family history and obesity in youth, their effect on acylcarnitine/aminoacids metabolomics and non-alcoholic fatty liver disease (NAFLD). Structural equation modeling approach

Date Published: February 21, 2018

Publisher: Public Library of Science

Author(s): Maria Elena Romero-Ibarguengoitia, Felipe Vadillo-Ortega, Augusto Enrique Caballero, Isabel Ibarra-González, Arturo Herrera-Rosas, María Fabiola Serratos-Canales, Mireya León-Hernández, Antonio González-Chávez, Srinivas Mummidi, Ravindranath Duggirala, Juan Carlos López-Alvarenga, Clemens Fürnsinn.


Structural equation modeling (SEM) can help understanding complex functional relationships among obesity, non-alcoholic fatty liver disease (NAFLD), family history of obesity, targeted metabolomics and pro-inflammatory markers. We tested two hypotheses: 1) If obesity precedes an excess of free fatty acids that increase oxidative stress and mitochondrial dysfunction, there would be an increase of serum acylcarnitines, amino acids and cytokines in obese subjects. Acylcarnitines would be related to non-alcoholic fatty disease that will induce insulin resistance. 2) If a positive family history of obesity and type 2 diabetes are the major determinants of the metabolomic profile, there would be higher concentration of amino acids and acylcarnitines in patients with this background that will induce obesity and NAFLD which in turn will induce insulin resistance.

137 normoglycemic subjects, mean age (SD) of 30.61 (8.6) years divided in three groups: BMI<25 with absence of NAFLD (G1), n = 82; BMI>30 with absence of NAFLD (G2), n = 24; and BMI>30 with NAFLD (G3), n = 31. Family history of obesity (any) was present in 53%. Both models were adjusted in SEM. Family history of obesity predicted obesity but could not predict acylcarnitines and amino acid concentrations (effect size <0.2), but did predict obesity phenotype. Family history of obesity is the major predictor of obesity, and the metabolic abnormalities on amino acids, acylcarnitines, inflammation, insulin resistance, and NAFLD.

Partial Text

Nearly a third of the world’s population is either obese or overweight [1,2]. Mexico ranks second worldwide in prevalence of combined overweight and obesity in adults at 71.3% [3–5]. Long-term weight loss maintenance is still a great challenge despite advances in the modalities to treat obesity [6].

We included 137 normoglycemic subjects, with a mean age of 30.61 (SD 8.6) years (Table 1), seventy percent were women. Group 1 (BMI<25) had 82 subjects; Group 2 (BMI >30) and Group 3 (BMI>30 and NAFLD) group had 24 and 31 subjects, respectively. Family history of obesity (any) was present in 53% of the total population, while family history of diabetes was present in 66%. Table 1 shows mean values of clinical, inflammatory and metabolomic parameters of the 3 groups and Table 2 shows the different degrees of family history of obesity and diabetes.

The presented SEM analysis evaluated hypothetical causal relationships of phenotypic, metabolomics, inflammatory markers and family history of obesity in an integrated model and found that the family history strongly correlates with a subject’s obesity.

Our study provides SEM that support that family History of obesity, correlates with patients obesity which results in several disruption in the regulation of key metabolic enzymes and pathways that predicts metabolomics (acylcarnitines and amino acids) and this predicts inflammation, insulin resistance, obesity and NAFLD.




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