The positive association of branched-chain amino acids and metabolic dyslipidemia in Chinese Han population

Abstract

BackgroundIt has been suggested that serum branched-chain amino acids (BCAAs) are associated with the incident, progression and prognostic of type 2 diabetes. However, the role of BCAAs in metabolic dyslipidemia (raised triglycerides (TG) and reduced high-density lipoprotein cholesterol (HDL-C)) remains poorly understood. This study aims to investigate 1) the association of serum BCAAs with total cholesterol (TC), TG, HDL-C and low-density lipoprotein cholesterol (LDL-C) and 2) the association between serum BCAAs levels and risk of metabolic dyslipidemia in a community population with different glucose homeostasis.MethodsDemographics data and blood samples were collected from 2251 Chinese subjects from the Huaian Diabetes Protective Program (HADPP) study. After exclusion for cardiovascular disease (CVD), serious hepatic or nephritic diseases and others, 1320 subjects remained for analysis (789 subjects with hemoglobin A1c (HbA1c) > 5.7, 521 with HbA1c ≤ 5.7). Serum BCAAs level was measured by liquid chromatography-tandem mass spectrometry (LC MS/MS). The association of BCAAs with lipids or with the risk of metabolic dyslipidemia was analyzed.ResultsElevated serum BCAAs (both total and individual BCAA) were positively associated with TG and inversely associated with HDL-C in the whole population. These correlations were still significant even after adjustment for confounding factors (r = 0.165, p < 0.001 for TG; and r = -0.126, p < 0.001 for HDL-C). For reduced HDL-C, we found higher odds risk (OR) of Valine (Val) in high HbA1c group than in the low one (OR = 1.055, p < 0.001 vs OR = 1.032, p = 0.059). Compared with that in the first quartile, the multivariable-adjusted OR (95 % CI) of the 4th quartile of serum total BCAAs level for reduced HDL-C was 3.689 (2.325, 5.854) in high HbA1c group and 2.329 (1.284, 4.227) in low group, for raised TG was 3.305 (2.120, 5.152) and 2.972 (1.706, 5.176), and for metabolic dyslipidemia was 3.703 (2.261, 6.065) and 3.702 (1.877, 7.304), respectively (all p < 0.01).ConclusionElevated serum BCAAs level are positively associated with incident metabolic dyslipidemia. In addition, glucose homeostasis could play a certain role in BCAAs-related dyslipidemia.

High dietary intake of branched‐chain amino acids is associated with an increased risk of insulin resistance in adults

“…1 Insulin resistance, as well as β-cell dysfunction, not only contribute to the progression of type 2 diabetes, 2 but are also important precursors of some chronic diseases, including hypertension, metabolic syndrome, dyslipidemia, and cardiovascular disease (CVD). [3][4][5] Insulin resistance has recently received considerable attention, and data reveal that nutritional factors, including food patterns, macronutrients, dietary fiber, and some micronutrients, may be associated with the development of IR. [6][7][8] Branched-chain amino acids (BCAAs), including leucine, isoleucine, and valine, are essential amino acids 9 frequently found in dietary protein, accounting for up to 15%-20% of protein intake, that have direct and indirect metabolic effects (e.g.…”

Association between dyslipidemia and plasma levels of branched-chain amino acids in the Japanese population without diabetes mellitus

“…5,6 A cross-sectional study by Yang et al revealed that increased total BCAA (T-BCAA) levels were associated with not only elevated TG levels but also reduced HDL-C levels and MD. 7 However, the relationship between individual BCAAs and reduced HDL-C levels was only reported in individuals with impaired glucose tolerance, and thus it remains unclear whether such an association exists in individuals without diabetes or impaired glucose tolerance. Regarding the relationship between BCAAs and LDL-C, Halama et al 8 reported that the by-products of leucine (Leu) degradation could serve as a substrate for cholesterol biosynthesis in vitro.…”

“…However, some studies found no correlation between serum BCAA and LDL-C levels. 7,9 To date, there is no consensus regarding the potential association between BCAAs and elevated LDL-C levels. Hence, further research is warranted to clarify the connection between BCAAs and dyslipidemia.…”

Linking of metabolomic biomarkers with cardiometabolic health in Chinese population

“…Some case‐control studies in Chinese populations also found correlations between certain metabolite signatures (including amino acids, acylcarnitines, lipids, organic acids and sugar metabolites) and obesity, prediabetes, T2D, diabetic complications, and CVD . In addition, in some cross‐sectional studies, circulating BCAAs were observed to be correlated with the risk of dyslipidemia, metabolic syndrome (MetS), and coronary artery disease (CAD) in Chinese subjects . However, these studies usually had a small sample size, and only a few studies investigated longitudinal associations of these biomarkers.…”

“…[14][15][16][17][18][19][20][21][22][23][24][25][26][27] In addition, in some cross-sectional studies, circulating BCAAs were observed to be correlated with the risk of dyslipidemia, metabolic syndrome (MetS), and coronary artery disease (CAD) in Chinese subjects. [28][29][30][31] However, these studies usually had a small sample size, and only a few studies investigated longitudinal associations of these biomarkers. In a recent prospective cohort study, a positive association was reported in 213 Chinese subjects among BCAAs and AAAs with future risk of T2D.…”