Central adiposity-induced plasma-free amino acid alterations are associated with increased insulin resistance in healthy Singaporean adults

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BACKGROUND/OBJECTIVES:Recent metabolomics technique reveals a plasma-free amino acid (PFAA)-based metabolite signature that is suggestive of altered PFAAs being an early manifestation of obesity-related insulin resistance. However, the PFAA profiles within non-obese, but more insulin-resistant Asians are not well researched. Compared with Caucasians, Asian populations have more central adiposity, which is generally regarded as metabolically more adverse, but the underlying mechanisms remain unclear. In the present study, we examined whether PFAA profiling was at least one important factor mediating central adiposity and insulin resistance, and aid in cardiovascular risk assessment in healthy Asians with normal body weight.SUBJECT/METHODS:This was a cross-sectional study. A total of 190 healthy men (n = 87 with a mean ± s.d. body mass index (BMI) of 23.5 ± 3.5 kg/m2) and women (n = 103 with a mean ± s.d. BMI of 21.4 ± 3.7 kg/m2) residing in Singapore took part in this study. PFAA levels were measured by using an amino acid analyzer. Basic anthropometric measurements, fasting blood glucose, fasting serum insulin and lipid profiles were obtained using standard protocols.RESULTS:Seven out of 18 amino acids were significantly correlated with measures of obesity (for example, waist circumference; waist-to-hip ratio and BMI) in current participants. Among them, the plasma concentrations of five amino acids, including Phe, Tyr, Met, Ala and His were positively associated with waist-to-hip ratio. With the exception of His, which had no association with insulin resistance, Phe, Tyr, Met and Ala were significantly associated with hyperinsulinemia and insulin resistance (P<0.05). In contrast, no associations were observed between circulating BCAAs (that is, Val, Leu, Ile), measures of obesity and insulin resistance. However, significant inverse associations were observed between BCAAs and total cholesterol and high-density lipoprotein.CONCLUSIONS:We found that central adiposity was associated with alterations of specific amino acids. As a result, PFAAs may serve as metabolite predictors of hyperglycemia, hyperinsulinemia and dyslipidemia in healthy participants.

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