Metabolic Phenotype of Obesity in a Saudi Population

Abstract

Metabolic phenotyping of obese populations can shed light on understanding environmental interactions underpinning obesogenesis. Obesity and its comorbidities are a major health and socioeconomic concern globally and are highly prevalent in the Middle East. We employed nuclear magnetic resonance spectroscopy to characterize the metabolic signature of urine and blood plasma for a cohort of obese (n = 50) compared to non-obese (n = 48) Saudi participants. The urinary metabolic phenotype of obesity was characterized by higher concentrations of N-acetyl glycoprotein fragments, bile acids, lysine, and methylamines and lower concentrations of tricarboxylic acid cycle intermediates, glycine, and gut microbial metabolites. The plasma metabolic phenotype of obesity was dominated by sugars, branched chain amino acids, and lipids, particularly unsaturated lipids, with lower levels of plasma phosphorylcholine and HDL. Serum hepatic enzymes, triglycerides, and cholesterol mapped to specific metabolic phenotypes, potentially indicating the dysregulation of multiple distinct obesity-related pathways. Differences between urine and plasma phenotypes of obesity for this Saudi population and that reported for Caucasian individuals indicate population disparities in pathways relating to ketogenesis (more apparent in the Saudi obese population), dysregulated liver function, and the gut microbiome. Mapping population-specific metabolic perturbations may hold promise in establishing population differences relevant to disease risk and stratification of individuals with respect to discovery of new therapeutic targets.

Gut microbiota-derived metabolites in obesity: a systematic review

“… - Positive correlations between CLA trans-9,trans-11-18:2 and E. ventriosum . - Ahmad et al (2016) [ 28 ] 50 participants with normal BMI (18.5 to <25 kg/m 2 ) and 50 obese (BMI > 30 kg/m 2 ) Fasting plasma and serum samples and urine specimens Untargeted: NMR-based metabolic profiling _ - ↑urinary excretion of hippurate, phenylacetylglutamine, 4-cresyl sulfate and formate in the lean group ↑urinary excretion of metabolites associated with bacterial degradation of choline such as TMA and DMA in the obese group ↓urinary excretion of indoxyl sulfate in the obese group Liu et al (2017) [ 9 ] 257 young Chinese obese individuals and lean controls Serum Untargeted: high performance liquid chromatograph (HPLC)-MS Targeted: ultra-high performance liquid chromatog­raphy (UHPLC) coupled to a Shimadzu 8050 Triple Quad mass spectrometry for amino acids shotgun sequencing - Negative correlations between phenylalanine, tyrosine, leucine, isoleucine and valine and Bacteroides species including B. thetaiotaomicron , B. intestina­lis , B. ovatus and B. uniformis - Negative correlations between glutamate and B. thetaiotaomicron - Positive correlations between glutamate and Ruminococcus sp., D. longicatena , C. comes ↑Phenylalanine, tyrosine, leucine, isoleucine, valine and glutamate in obese Org et al (2017) [ 20 ] 531 middle-aged Finnish men Serum and plasma Targeted: nuclear magnetic resonance (NMR) spectroscopy platform for lipids, lipoproteins, fatty acids, amino acids, ketone bodies and glycolysis precursor molecules and liquid chromatography with on-line tandem mass spectrometry (LC-MS/MS) for TMAO, choline, betaine, and carnitine 16S ribosomal RNA gene sequencing - correlation between acetate and microbial diversity - Po...…”

“…Most of the included studies compared metabolites in overweight or obese individuals with normal weight controls in different populations, including Chinese [ 9 ], Finnish [ 19 , 20 , 21 , 22 ], Swiss [ 23 ], American [ 24 ], Italian [ 25 ], Canadian [ 26 ], Mexican [ 27 ], and Arabian [ 28 ] populations. The age range varied from school-age children [ 23 , 27 ] to young and middle age adults [ 9 , 19 , 20 , 21 , 24 , 25 , 26 , 28 , 29 ]. One study investigated obese women in early pregnancy [ 22 ].…”

“…The analytical platforms applied for targeted metabolic profiling consisted of ultra-high-performance liquid chromatography (UHPLC) coupled to triple quadrupole mass spectrometry (UPLC-QqQMS) [ 9 , 19 ], gas-liquid chromatography [ 21 , 29 ], high-pressure liquid chromatography (HPLC) [ 21 , 23 ], nuclear magnetic resonance (NMR) spectroscopy [ 20 ], liquid chromatography with on-line tandem mass spectrometry (LC-MS/MS) [ 20 ], gas chromatography-mass spectrometry (GC-MS) [ 21 , 26 , 27 ], and a pulsed electrochemical detector [ 21 ]. The platforms for untargeted metabolic detection included gas chromatography coupled to time-of-flight mass spectrometry (GC_GC-TOFMS) [ 19 ], ultra-performance liquid chromatography coupled to quadrupole-TOFMS (UPLC-QTOFMS) [ 19 ], HPLC-MS [ 9 ], high-throughput proton NMR metabolomics [ 22 ], LC-MS [ 24 ], high-resolution proton NMR (1H NMR) spectroscopy [ 25 ], and NMR-based metabolic profiling [ 28 ]. The most used method for fecal microbiota analysis was 16S ribosomal RNA amplicon sequencing [ 20 , 22 , 24 , 27 ], and the other techniques included shotgun sequencing [ 9 , 24 ], quantitative real-time PCR [ 21 , 23 , 29 ], denaturing gradient gel electrophoresis (DGGE) [ 19 ], phylogenetic microarray [ 29 ], temperature gradient gel electrophoresis (TGGE) [ 23 ], and multi-tag pyro-sequencing [ 26 ].…”

“…The other AA-derived metabolite is indoxyl sulfate, a metabolite of dietary L-tryptophan, which is catalyzed by tryptophanase produced by gut microbiota [ 59 ]. Ahmad et al [ 28 ] reported decreased excretion of indoxyl sulfate in obese subjects. An inverse relationship of indoxyl sulfate with BMI has also been shown in other animal and human studies [ 60 , 61 ].…”

Quantitative In-Vitro Diagnostic NMR Spectroscopy for Lipoprotein and Metabolite Measurements in Plasma and Serum: Recommendations for Analytical Artifact Minimization with Special Reference to COVID-19/SARS-CoV-2 Samples

“… 1 − 3 1 H NMR-spectroscopy of biofluids including blood plasma and serum have been widely used to investigate systemic biochemistry in health and disease for decades. 1 , 4 − 6 Plasma NMR studies, in particular, have proved useful in diabetes, 5 , 7 obesity, 9 , 10 rheumatoid arthritis, 11 cancers 12 infectious diseases 13 rare diseases, 14 , 15 and neurological conditions. 16 , 17 Despite previous attempts at method and data harmonization, metabolic phenotyping still does not have uniformly applied standards as the analytical platforms and methods used are often locally optimized for each laboratory or research group.…”