Alloisoleucine Differentiates the Branched-chain Aminoacidemia of Zucker and Dietary Obese Rats

Objective: Circulating branched-chain amino acids (BCAAs) are elevated in obesity and this has been linked to obesity comorbidities. However it is unclear how obesity affects alloisoleucine, a BCAA and pathognomonic marker of branched-chain keto acid dehydrogenase complex (BCKDC) disorders. It has been previously established that obese Zucker rats exhibit BCKDC impairments in fat and other tissues, whereas BCKDC impairments in adipose tissue of DIO rats are compensated by increased hepatic BCKDC activity. Therefore, alloisoleucine was investigated in these two obesity models. Methods: Amino acids were extracted from plasma and measured using ultra performance liquid chromatography mass spectrometry. Results: Plasma alloisoleucine was 238% higher in obese compared to lean Zucker rats. This elevation was greater than that of other BCAAs (107-124%). DIO rats had no significant change in alloisoleucine, despite elevations in other BCAAs (15-66%). Conclusions: Alloisoleucine was elevated in obese Zucker but not DIO rats consistent with known global impairments of BCKDC in Zucker but not DIO rats. Cytotoxic branched-chain ketoacids (BCKAs) accumulate in genetic disorders affecting BCKDC. BCKAs increase reactive oxygen species, stress kinase activation, and mitochondrial dysfunction. Inasmuch as these factors underlie obesity comorbidities, it may important to identify obese individuals with elevated alloisoleucine.