Adipose transplant for inborn errors of branched chain amino acid metabolism in mice

Mol Genet Metab. 2013 Aug;109(4):345-53. doi: 10.1016/j.ymgme.2013.05.010. Epub 2013 May 30.


Liver transplantation appears to be quite beneficial for treatment of maple syrup urine disease (MSUD, an inherited disorder of branched chain amino acid metabolism); however, there is a limited availability of donor livers worldwide and the first year costs of liver transplants are quite high. Recent studies have suggested that intact adipose tissue, already widely used in reconstructive surgery, may have an underappreciated high capacity for branched chain amino acid (BCAA) metabolism. Here we examined the potential for adipose tissue transplant to lower circulating BCAAs in two models of defective BCAA metabolism, BCATm and PP2Cm [branched chain keto acid dehydrogenase complex (BCKDC) phosphatase] knockout (KO) mice. After 1-2g fat transplant, BCATm and PP2Cm KO mice gained or maintained body weight 3weeks after surgery and consumed similar or more food/BCAAs the week before phlebotomy. Transplant of fat into the abdominal cavity led to a sterile inflammatory response and nonviable transplanted tissue. However when 1-2g of fat was transplanted subcutaneously into the back, either as small (0.1-0.3g) or finely minced pieces introduced with an 18-ga. needle, plasma BCAAs decreased compared to Sham operated mice. In two studies on BCATm KO mice and one study on PP2Cm KO mice, fat transplant led to 52-81% reductions in plasma BCAAs compared to baseline plasma BCAA concentrations of untreated WT type siblings. In PP2Cm KO mice, individual BCAAs in plasma were also significantly reduced by fat transplant, as were the alloisoleucine/Phe ratios. Therefore, subcutaneous fat transplantation may have merit as an adjunct to dietary treatment of MSUD. Additional studies are needed to further refine this approach.

Keywords: Adipose tissue; Alloisoleucine; BCAA; BCATc or BCATm; BCKA; BCKD; Branched chain amino acids; Exp; KO; MSUD; Maple syrup urine disease; Mice; PP2Cm; Transplantation; WT; branched chain keto acids; branched-chain amino acids; branched-chain keto acid dehydrogenase complex; branched-chain keto acid dehydrogenase phosphatase (gene name: PPM1K); experiment; knock out mouse; maple syrup urine disease; the cytosolic or mitochondrial isoform of branched-chain amino acid transaminase respectively (gene names: BCAT1 for BCATc, BCAT2 for BCATm); wildtype sibling mice homozygous for wild type allele.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • 3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide) / blood
  • 3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide) / genetics
  • 3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide) / metabolism
  • 3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide) / therapeutic use
  • Adipose Tissue / metabolism
  • Adipose Tissue / transplantation*
  • Amino Acid Metabolism, Inborn Errors / blood
  • Amino Acid Metabolism, Inborn Errors / genetics
  • Amino Acid Metabolism, Inborn Errors / therapy
  • Animals
  • Maple Syrup Urine Disease / blood
  • Maple Syrup Urine Disease / genetics
  • Maple Syrup Urine Disease / metabolism*
  • Maple Syrup Urine Disease / therapy*
  • Mice
  • Mice, Knockout
  • Transaminases / blood
  • Transaminases / genetics
  • Transaminases / metabolism*
  • Transaminases / therapeutic use


  • 3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide)
  • Transaminases
  • branched-chain-amino-acid transaminase