Background: Obesity is a heterogeneous disease with different phenotypes based on physiological and biological differences in energy intake and expenditure. A recent study determined that guided therapy based on the classification of obesity phenotypes achieved better outcomes with respect to body weight loss (Acosta et al 2021). We aimed to identify potential circulating biomarkers to predict phenotypes and susceptibility to comorbidities.
Methods: In a randomized placebo-controlled study which enrolled overweight and obese participants with T2DM, 18 subjects was subphenotype into 3 groups: hungry brain (HB) N=5, hungry gut (HG) N=5 and slow burn (SB) N=5 and unclassified N=3. Global plasma metabolomics and proteomics analysis were performed at baseline to identify the molecular signatures associated with each phenotype.
Results: In the metabolomics analysis with p<0.05 cutoff, SB had lower homocysteine by 46% vs. HB. In contrast, SB had higher levels of proline, Lauroyl-L-carnitine and DL-2-Aminocaprylic acid (by 43%, 385% and 476% respectively) vs. HB. Consistently, SB had also increased levels of proline by 43% p<0.43 vs. HG. In the proteomics analysis with p<0.05 cutoff, Apolipoprotein M (APOM) decreased in SB by 39% with concomitant lipid oxidation protein (PCYNOX1) decreased by 40% vs. HB. Lower CV risks biomarkers of homocysteine and PCYNOX1 have been observed in SB. In contrast, SB had higher levels of liver collagen synthesis, and liver fat accumulation biomarkers (proline, Lauroyl-L-carnitine, and DL-2-Aminocaprylic acid.
Conclusions: These results suggest there may be some differential circulating biomarkers in different phenotypes that are susceptible to comorbidity differences such as CV and NASH-related risks. Further exploration of these differences may help better
understand metabolic mechanisms in these groups and permit more targeted therapy in the future. Larger studies are required to substantiate these findings.
W. Qi: Employee; AstraZeneca. X. Tu: Employee; AstraZeneca. D. Robertson: Employee; AstraZeneca. Stock/Shareholder; AstraZeneca. A. Acosta: Consultant; Amgen Inc., Regeneron Pharmaceuticals Inc., Nestlé Health Science, Structure Therapeutics, Inc., Boehringer-Ingelheim. Research Support; Vivus. Consultant; Currax. Other Relationship; Gila Therapeutics, Phenomix Sciences. Speaker's Bureau; Eli Lilly and Company. V.E. Parker: Employee; AstraZeneca. Stock/Shareholder; AstraZeneca.
