Plasma amino acid profile is associated with visceral fat accumulation in obese Japanese subjects

Abstract

SummaryMetabolic complications associated with obesity are becoming more common among Japanese subjects. However, visceral fat accumulation is not always apparent by measuring body mass index (BMI) or waist circumference in Asian populations because of the physiological characteristics particular to those ethnicities. Excess visceral fat accumulation raises the odds ratio for developing cardiovascular disease. Thus, high-throughput determination of the amount of abdominal adipose tissue is necessary. We hypothesized that accumulating visceral fat alters the peripheral amino acid profile and that a multivariate logistic regression model of plasma free amino acids can distinguish visceral obesity. A total of 1449 Japanese subjects (985 males and 464 females) who had undergone a comprehensive health screening were enrolled in this study. The visceral fat area was determined using computed tomography imaging, and a plasma free amino acid index to identify high visceral fat areas (Ն100 cm 2 ) was developed. The sensitivity and specificity values of the generated amino acid index were 80% and 65%, respectively. In particular, the sensitivity of the generated index to identify subjects with non-apparent visceral obesity (BMI < 25 kg m -2 ; visceral fat area Ն 100 cm 2 ) was much greater than that of the waist circumference (73% vs. 46%, respectively). This index's high sensitivity and specificity may be the result of specific alterations in the patients' amino acid profiles, which were specifically correlated with the visceral fat areas and not with subcutaneous fat areas. This profile can be used as a predictor of elevated visceral obesity and a risk assessment tool for metabolic complications in Asian populations.Keywords: CT scan, high-throughput risk screening, non-apparent visceral obesity, plasma amino acid. What is already known about this subject• Asians with metabolic complications associated with obesity, a low body mass index and a low waist circumference have a greater proportion of visceral adipose tissue for a given amount of total body fat compared with Europeans.• Apparent obese humans and obese animal models show an elevation of branched-chain amino acid levels in plasma.• A multivariate logistic regression model of plasma free amino acids has been used to screen for several types of cancers in clinical settings. What this study adds• A specific formula incorporating six amino acid values (Ala, Gly, Glu, Trp, Tyr and branched-chain amino acid) was developed for discrimination of subjects with high visceral fat area by multivariate logistic regression analyses.• The generated amino acid formula was strongly correlated with visceral fat area in both apparent and non-apparent obese subjects.• Measuring plasma free amino acids can be used to distinguish the non-apparent visceral obesity in clinical settings in Asian populations.clinical obesity

Alterations of plasma metabolite profiles related to adipose tissue distribution and cardiometabolic risk

“…While many studies have focused on plasma metabolite alterations in obesity, insulin resistance, and type 2 diabetes, only a few studies have considered body fat distribution, other markers of cardiometabolic risk (13,44,55), and possible depot-specific alterations in BCAA-catabolizing enzymes (15,19). In addition, only one study has performed metabolomicsbased AA analysis including human visceral and subcutaneous adipose tissue from nonobese and obese individuals (13).…”

The influence of a 3-week body mass reduction program on the metabolic parameters and free amino acid profiles in adult Polish people with obesity

“…22 An elevation of the BCAA levels has been reported in humans with obesity and in animal models of obesity, and many studies have described a decrease in the levels of BCAAs after weight loss. 12,[22][23][24] Some studies demonstrated a decrease in concentrations of BCAA and metabolites derived from BCAA oxidation after bariatric surgery. 25,26 The increased plasma BCAA concentration may be the result of the impaired BCAA-catabolizing capacity of the adipose tissue, an improper high-fat and highprotein diet (dietary protein comprised of >20% BCAA) and increased catabolic pathways of BCAAs.…”

“…12 Moreover, Yamakado et al hypothesized that the amount of visceral fat changes AA profile, and that the multivariate logistic regression model of free AAs in plasma can discern non-apparent visceral obesity in adult Asian individuals. 12 The associations between the BCAA levels and tyrosine with visceral adiposity -irrespective of ethnicity, lifestyle or environmental conditions -were also studied by Marti et al 13 Despite the great interest in and development of the state of knowledge about metabolic profiles in people with obesity, the perturbations in AA concentrations in the serum of adult patients suffering from obesity after weight loss are not fully understood. The previous studies in this area focused on describing the changes in metabolic profile after weight loss achieved by bariatric surgery or longterm body mass reduction programs based on lifestyle intervention.…”

The Omics of Obesity

“…First, certain types of gut microbiota may be more efficient in extracting energy out of food that passes through the gut and therefore make available more energy for the host in which they reside. Bomb calorimetry analysis measuring the energy content of faeces revealed that ob/ob mice have significantly less energy remaining in their faeces relative to their lean littermates suggestive that the microbiota within ob/ob mice are better at harvesting and extracting energy from the food within their digestive tract [60]. Other possibilities include the role of inflammation.…”

“…Germ-free mice receiving microbiota transplants by oral gavage with microbiota either sourced from genetically obese ob/ob mice or lean mice have demonstrated that recipients of the ob/ob microbiota put on more body fat in the weeks after being inoculated as compared to those who received the "lean" microbiota transplant [60]. 16S-rRNA-gene-sequence-based analysis of samples obtained in this study demonstrated that the ob/ob donor microbiota samples had a greater abundance of firmicutes bacteria compared with that of the lean donor microbiota samples [60] indicating the possibility that enriching the gut with firmicutes may drive the body weight phenotype. Indeed a number of rodent studies have raised the possibility that the ratio of the phyla bacteroidetes to that of the phyla firmicutes is associated with obesity.…”