Branched-Chain Amino Acid Levels Are Related with Surrogates of Disturbed Lipid Metabolism among Older Men

Abstract

Aims/hypothesisExisting studies suggest that decreased branched-chain amino acid (BCAA) catabolism and thus elevated levels in blood are associated with metabolic disturbances. Based on such information, we have developed a hypothesis how BCAA degradation mechanistically connects to tricarboxylic acid cycle, intramyocellular lipid storage, and oxidation, thus allowing more efficient mitochondrial energy production from lipids as well as providing better metabolic health. We analyzed whether data from aged Finnish men are in line with our mechanistic hypothesis linking BCAA catabolism and metabolic disturbances.MethodsOlder Finnish men enriched with individuals having been athletes in young adulthood (n = 593; mean age 72.6 ± 5.9 years) responded to questionnaires, participated in a clinical examination including assessment of body composition with bioimpedance and gave fasting blood samples for various analytes as well as participated in a 2-h 75 g oral glucose tolerance test. Metabolomics measurements from serum included BCAAs (isoleucine, leucine, and valine).ResultsOut of the 593 participants, 59 had previously known type 2 diabetes, further 67 had screen-detected type 2 diabetes, 127 impaired glucose tolerance, and 125 impaired fasting glucose, while 214 had normal glucose regulation and one had missing glucose tolerance information. There were group differences in all of the BCAA concentrations (p ≤ 0.005 for all BCAAs), such that those with normal glucose tolerance had the lowest and those with diabetes mellitus had the highest BCAA concentrations. All BCAA levels correlated positively with body fat percentage (r = 0.29–0.34, p < 0.0001 for all). Expected associations with high BCAA concentrations and unfavorable metabolic profile indicators from metabolomics analysis were found. Except for glucose concentrations, the associations were stronger with isoleucine and leucine than with valine.Conclusion/interpretationThe findings provided further support for our hypothesis by strengthening the idea that the efficiency of BCAA catabolism may be mechanistically involved in the regulation of fat oxidation, thus affecting the levels of metabolic disease risk factors.

Branched-Chain Amino Acid Catabolism Impacts Triacylglycerol Homeostasis in Chlamydomonas reinhardtii

“…In mammalian cells, since fatty acid b-oxidation occurs essentially in mitochondria (Eaton et al, 1996), the metabolic link between storage lipid degradation and mitochondrial activity has been well established (Kujala et al, 2016). Based on our analysis and also based on the literature, BCAA degradation generally occurs in mitochondria, whereas the major steps for b-oxidation of fatty acids occur in peroxisomes of Chlamydomonas (Kong et al, 2017(Kong et al, , 2018a(Kong et al, , 2018b.…”

Plasma branched chain/aromatic amino acids, enriched Mediterranean diet and risk of type 2 diabetes: case-cohort study within the PREDIMED Trial

“…Randomised dietary interventions (in weight-loss trials) showed that decreases in plasma tyrosine were associated with improvements in insulin resistance independent of weight loss [32]. This evidence, together with parallel results in obese children [33] and evidence on BCAA-associated metabolic disorders in elderly participants [34], supports a causal role for BCAAs in the development of insulin resistance and type 2 diabetes, independently of weight change.…”

Metabolite biomarkers of type 2 diabetes mellitus and pre-diabetes: a systematic review and meta-analysis

“…As shown in Table 2 , there were 14 studies of pre-diabetes included in the meta-analysis, which contained a total of 2139 prediabetic patients and 4844 healthy controls [ 22 , 24 , 25 , 29 , 44 – 53 ]. Among these studies, one was a cross-sectional study [ 22 ], two were follow-up studies [ 29 , 39 ], one was a longitudinal study [ 53 ], one was a cohort study [ 50 ], and the remaining nine were case-control studies.…”