Associations between branched chain amino acid levels, obesity and cardiometabolic complications

Aim/hypothesis: Leucine, isoleucine and valine are branched chain amino acids (BCAA). BCAAs areamong the 9 essential amino acids and are associated with beneficial health effects. However, previous studies have reported strong associations between increased BCAA levels, obesity and metabolic diseases such as type 2 diabetes. The objective of this study is to investigate the association between plasma BCAA levels, cardiometabolic risk factors and Metabolic Syndrome (MetS) in normal versus overweight/obese subjects. Methods: Mass spectrometry-based metabolite profiling of 200 samples using the Absolute ID p180 Kit was used to compare plasma BCAA levels between overweight/obese subjects with or without MetS and normal weight subjects without MetS. Results: Overweight/obese participants irrespective of their MetS status have higher plasma BCAA levels than normal weight participants (P<0.0001). Obesity-associated MetS appears to worsen the difference with normal weight subjects. Leucine (P=0.005) and isoleucine (P=0.02) levels are correlated with HOMA-IR among obese individuals without MetS. Among obese subjects with MetSleucine levels (P=0.04) are correlated to HOMA-IR whereas leucine and isoleucine are correlated with plasma glucose levels. Conclusions/interpretation: BCAAs are associated with obesity and MetS. Also, these results suggest that analyzing BCAAs separately may help for a better understanding of the association between BCAAs obesity and Mets. Abbreviations: BCAA: Branched Chain Amino Acid; CVD: Cardio Vascular Disease; DBP: Diastolic Blood Pressure; IR: Insulin Resistance; MetS: Metabolic Syndrome; SBP: Systolic Blood Pressure; Total-C: Total Cholesterol; Tg: Triglycerides; T2D: Type 2 Diabetes; WC: Waist Circumference Introduction In recent years, the prevalence of metabolic syndrome (MetS) paralleled the increase in the prevalence of obesity. The MetS is characterized by the clustering of abdominal obesity, dyslipidemia, insulin resistance (IR) and hypertension [1]. These conditions are associated with chronic diseases including cardiovascular disease (CVD), type 2 diabetes (T2DM) and hypertension [2,3]. Several studies reported differences in plasma metabolite composition between obese and non-obese individuals.Specific metabolite signatures including amino acids, acylcarnitines or glycerophospholipids have been associated with obesity [4,5]. Leucine, isoleucine and valine are collectively referred as BCAAs due to their shared structural features in side-chain and a common catabolic pathway [6]. They are 3 of the 9 essential amino acids and are abundant in the diet representing up to 15-25% of total protein intake [7]. BCAA-rich diets are often associated with beneficial health effects [8,9]. Isoleucine have hypoglycemic effects in muscles and plays a role in the depression of gluconeogenesis rat liver [7]. BCAAs also promote protein synthesis, cellular metabolism and cell growth [10,11]. However, despite these effects on metabolic health, several studies have indicated that increased fasting levels of circulating BCAAs are associated with poor metabolic health. For instance, Yang et al. showed a positive and significant association between plasma BCAA levels and CVD risk factors [12]. Newgard et al. reported that increased BCAA levels are associated with high risk of T2DM and IR in humans and animals [5]. Therefore, the aim of the present study was to investigate the relationship between plasma BCAA levels, obesity and MetS status. Methods Subjects Men (n=101) and women (n=99) enrolled in the present study were aged between 18 and 55 years as previously described [13]. This study was divided into two recruitment phases: from May 2004 to December 2004 and from March 2006 to April 2007. Participants were recruited in the Quebec City metropolitan area using advertisements in Correspondence to: Marie-Claude Vohl, Institute of Nutrition and Functional Foods (INAF), Laval University 2440 Hochelaga Blvd, Quebec, Canada, Tel: 418656-2131, Extn: 4676; E-mail: [email protected]