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AMPK activation increases uncoupling protein‐3 expression and mitochondrial enzyme activities in rat muscle without fibre type transitions
Author(s) -
Putman Charles T.,
Kiricsi Mónika,
Pearcey Jean,
MacLean Ian M.,
Bamford Jeremy A.,
Murdoch Gordon K.,
Dixon Walter T.,
Pette Dirk
Publication year - 2003
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1111/j.1469-7793.2003.00169.x
Subject(s) - ampk , microbiology and biotechnology , enzyme , uncoupling protein , protein expression , mitochondrion , chemistry , medicine , endocrinology , biophysics , biology , biochemistry , protein kinase a , gene , adipose tissue , brown adipose tissue
The present study examined the effect of chronic activation of 5′‐AMP‐activated protein kinase (AMPK) on the metabolic profile, including uncoupling protein‐3 (UCP‐3) and myosin heavy chain (MHC)‐based fibre phenotype of rodent fast‐twitch tibialis anterior muscle. Sprague‐Dawley rats were given daily injections of 5‐aminoimidazole‐4‐carboxamide‐1‐β‐D‐ribofuranoside (AICAR), a known activator of AMPK, or vehicle (control) for 28 days. After AICAR treatment, UCP‐3 expression at the mRNA level was elevated 1.6 ± 0.1‐fold ( P < 0.006) and corresponded to a 3.3 ± 0.2‐fold increase in UCP‐3 protein content ( P < 0.0001). In addition, the activities of the mitochondrial reference enzymes citrate synthase (EC 4.1.3.7) and 3‐hydroxyacyl‐CoA‐dehydrogenase (EC 1.1.1.35), which are known to increase in proportion to mitochondrial volume density, were elevated 1.6‐fold ( P < 0.006), while the activity of lactate dehydrogenase (EC 1.1.1.27) was reduced to 80 % of control ( P < 0.02). No differences were detected after AICAR treatment in the activities of the glycolytic reference enzymes glyceraldehydephosphate dehydrogenase (EC 1.2.1.12) or phosphofructokinase (EC 2.7.1.11), nor were MHC‐based fibre‐type transitions observed, using immunohistochemical or electrophoretic analytical methods. These changes could not be attributed to variations in inter‐organ signalling by metabolic substrates or insulin. We conclude that an AMPK‐dependent pathway of signal transduction does mimic some of the metabolic changes associated with chronic exercise training, but does not affect expression of the MHC‐based structural phenotype. Thus, the metabolic and MHC‐based fibre types do not appear to be regulated in a co‐ordinated way, but may be independently modified by different signalling pathways.