title: Branched-Chain Amino Acid Levels Are Related with Surrogates of Disturbed Lipid Metabolism among Older Men.
abstract: OBJECTIVE
  Existing 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.
  
  
  METHODS
  Older 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).
  
  
  RESULTS
  Out 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.
  
  
  CONCLUSIONS
  The 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.
authors.affiliation: Department of Health Sciences, University of Jyväskylä , Jyväskylä , Finland.
authors.forename: Urho M
authors.initials: UM
authors.lastname: Kujala
authors.affiliation: Diabetes Prevention Unit, Department of Chronic Disease Prevention, Division of Welfare and Health Promotion, National Institute for Health and Welfare , Helsinki , Finland.
authors.forename: Markku
authors.initials: M
authors.lastname: Peltonen
authors.affiliation: Department of General Practice and Primary Health Care, Helsinki University Hospital, University of Helsinki, Helsinki, Finland; Vantaa Health Center, Vantaa, Finland.
authors.forename: Merja K
authors.initials: MK
authors.lastname: Laine
authors.affiliation: Department of Public Health, University of Helsinki, Helsinki, Finland; Department of Health, National Institute for Health and Welfare, Helsinki, Finland; Institute for Molecular Medicine, University of Helsinki, Helsinki, Finland.
authors.forename: Jaakko
authors.initials: J
authors.lastname: Kaprio
authors.affiliation: Department of Health and Physical Activity, Paavo Nurmi Centre, University of Turku , Turku , Finland.
authors.forename: Olli J
authors.initials: OJ
authors.lastname: Heinonen
authors.affiliation: Genomics and Biomarkers Unit, Department of Health, National Institute for Health and Welfare , Helsinki , Finland.
authors.forename: Jouko
authors.initials: J
authors.lastname: Sundvall
authors.affiliation: Diabetes Prevention Unit, Department of Chronic Disease Prevention, Division of Welfare and Health Promotion, National Institute for Health and Welfare, Helsinki, Finland; Department of General Practice and Primary Health Care, Helsinki University Hospital, University of Helsinki, Helsinki, Finland; Folkhälsan Research Center, Helsinki, Finland.
authors.forename: Johan G
authors.initials: JG
authors.lastname: Eriksson
authors.affiliation: Population Research Unit, Department of Chronic Disease Prevention, National Institute for Health and Welfare , Turku , Finland.
authors.forename: Antti
authors.initials: A
authors.lastname: Jula
authors.affiliation: Department of Public Health, University of Helsinki , Helsinki , Finland.
authors.forename: Seppo
authors.initials: S
authors.lastname: Sarna
authors.affiliation: Department of Biology of Physical Activity, University of Jyväskylä , Jyväskylä , Finland.
authors.forename: Heikki
authors.initials: H
authors.lastname: Kainulainen
keywords: branched-chain amino acids; energy metabolism; lipid oxidation; metabolic disease; mitochondria; tricarboxylic acid cycle