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ACC2 is expressed at high levels in human white adipose and has an isoform with a novel N-terminus [corrected].

Castle JC, Hara Y, Raymond CK, Garrett-Engele P, Ohwaki K, Kan Z, Kusunoki J, Johnson JM - PLoS ONE (2009)

Bottom Line: We find, however, that human adipose tissue, unlike rodent adipose, expresses more ACC2 mRNA relative to the oxidative tissues muscle and heart.Both ACC2 isoforms are capable of de novo lipogenesis, suggesting that ACC2, in addition to ACC1, may play a role in lipogenesis.The results demonstrate a significant difference in ACC expression between human and rodents, which may introduce difficulties for the use of rodent models for development of ACC inhibitors.

View Article: PubMed Central - PubMed

Affiliation: Rosetta Inpharmatics LLC, Seattle, Washington, United States of America. john_castle@merck.com

ABSTRACT
Acetyl-CoA carboxylases ACC1 and ACC2 catalyze the carboxylation of acetyl-CoA to malonyl-CoA, regulating fatty-acid synthesis and oxidation, and are potential targets for treatment of metabolic syndrome. Expression of ACC1 in rodent lipogenic tissues and ACC2 in rodent oxidative tissues, coupled with the predicted localization of ACC2 to the mitochondrial membrane, have suggested separate functional roles for ACC1 in lipogenesis and ACC2 in fatty acid oxidation. We find, however, that human adipose tissue, unlike rodent adipose, expresses more ACC2 mRNA relative to the oxidative tissues muscle and heart. Human adipose, along with human liver, expresses more ACC2 than ACC1. Using RT-PCR, real-time PCR, and immunoprecipitation we report a novel isoform of ACC2 (ACC2.v2) that is expressed at significant levels in human adipose. The protein generated by this isoform has enzymatic activity, is endogenously expressed in adipose, and lacks the N-terminal sequence. Both ACC2 isoforms are capable of de novo lipogenesis, suggesting that ACC2, in addition to ACC1, may play a role in lipogenesis. The results demonstrate a significant difference in ACC expression between human and rodents, which may introduce difficulties for the use of rodent models for development of ACC inhibitors.

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Expression of ACC1 and ACC2 mRNA isoforms in human, mouse, and rat tissues.TaqMan probes were designed to specifically monitor each transcript and were calibrated using standard curves (see Methods). Expression levels were scaled for each species such that the maximum ACC1 or total ACC2 expression (ACC2.v1 plus ACC2.v2) is 100.
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pone-0004369-g003: Expression of ACC1 and ACC2 mRNA isoforms in human, mouse, and rat tissues.TaqMan probes were designed to specifically monitor each transcript and were calibrated using standard curves (see Methods). Expression levels were scaled for each species such that the maximum ACC1 or total ACC2 expression (ACC2.v1 plus ACC2.v2) is 100.

Mentions: The relative abundances of ACC1, ACC2.v1 and ACC2.v2 transcripts were measured in five human tissues using calibrated real-time RT-PCR. As shown in Figure 3 (top), the human ACC2.v2 transcript is less abundant than the known isoform but is significantly expressed in all five tissues tested. The highest absolute expression level of ACC2.v2 is observed in adipose tissue, where the splice variant accounts for over 20% of ACC2 expression, at levels comparable to ACC1 expression. We also measured the levels of ACC1, ACC2.v1, and ACC2.v2 in corresponding mouse and rat tissues (Figures 3, middle and lower). The ratio of ACC1 and ACC2 expression is dramatically different between rodent tissues and human tissues, particularly in the lipogenic tissues adipose and liver. Unlike human tissues, both rat and mouse adipose express ACC2 at low levels, significantly lower than ACC1, and rodent liver contains more ACC1 than ACC2. Furthermore, rodent muscle expresses ACC2 at levels much higher than seen in rodent adipose, different from the pattern in humans. Finally, the ratio of ACC2.v1 to ACC2.v2 transcript expression is similar in rodent and human tissues, further suggesting that the novel ACC2.v2 product is regulated and may be functional.


ACC2 is expressed at high levels in human white adipose and has an isoform with a novel N-terminus [corrected].

Castle JC, Hara Y, Raymond CK, Garrett-Engele P, Ohwaki K, Kan Z, Kusunoki J, Johnson JM - PLoS ONE (2009)

Expression of ACC1 and ACC2 mRNA isoforms in human, mouse, and rat tissues.TaqMan probes were designed to specifically monitor each transcript and were calibrated using standard curves (see Methods). Expression levels were scaled for each species such that the maximum ACC1 or total ACC2 expression (ACC2.v1 plus ACC2.v2) is 100.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2629817&req=5

pone-0004369-g003: Expression of ACC1 and ACC2 mRNA isoforms in human, mouse, and rat tissues.TaqMan probes were designed to specifically monitor each transcript and were calibrated using standard curves (see Methods). Expression levels were scaled for each species such that the maximum ACC1 or total ACC2 expression (ACC2.v1 plus ACC2.v2) is 100.
Mentions: The relative abundances of ACC1, ACC2.v1 and ACC2.v2 transcripts were measured in five human tissues using calibrated real-time RT-PCR. As shown in Figure 3 (top), the human ACC2.v2 transcript is less abundant than the known isoform but is significantly expressed in all five tissues tested. The highest absolute expression level of ACC2.v2 is observed in adipose tissue, where the splice variant accounts for over 20% of ACC2 expression, at levels comparable to ACC1 expression. We also measured the levels of ACC1, ACC2.v1, and ACC2.v2 in corresponding mouse and rat tissues (Figures 3, middle and lower). The ratio of ACC1 and ACC2 expression is dramatically different between rodent tissues and human tissues, particularly in the lipogenic tissues adipose and liver. Unlike human tissues, both rat and mouse adipose express ACC2 at low levels, significantly lower than ACC1, and rodent liver contains more ACC1 than ACC2. Furthermore, rodent muscle expresses ACC2 at levels much higher than seen in rodent adipose, different from the pattern in humans. Finally, the ratio of ACC2.v1 to ACC2.v2 transcript expression is similar in rodent and human tissues, further suggesting that the novel ACC2.v2 product is regulated and may be functional.

Bottom Line: We find, however, that human adipose tissue, unlike rodent adipose, expresses more ACC2 mRNA relative to the oxidative tissues muscle and heart.Both ACC2 isoforms are capable of de novo lipogenesis, suggesting that ACC2, in addition to ACC1, may play a role in lipogenesis.The results demonstrate a significant difference in ACC expression between human and rodents, which may introduce difficulties for the use of rodent models for development of ACC inhibitors.

View Article: PubMed Central - PubMed

Affiliation: Rosetta Inpharmatics LLC, Seattle, Washington, United States of America. john_castle@merck.com

ABSTRACT
Acetyl-CoA carboxylases ACC1 and ACC2 catalyze the carboxylation of acetyl-CoA to malonyl-CoA, regulating fatty-acid synthesis and oxidation, and are potential targets for treatment of metabolic syndrome. Expression of ACC1 in rodent lipogenic tissues and ACC2 in rodent oxidative tissues, coupled with the predicted localization of ACC2 to the mitochondrial membrane, have suggested separate functional roles for ACC1 in lipogenesis and ACC2 in fatty acid oxidation. We find, however, that human adipose tissue, unlike rodent adipose, expresses more ACC2 mRNA relative to the oxidative tissues muscle and heart. Human adipose, along with human liver, expresses more ACC2 than ACC1. Using RT-PCR, real-time PCR, and immunoprecipitation we report a novel isoform of ACC2 (ACC2.v2) that is expressed at significant levels in human adipose. The protein generated by this isoform has enzymatic activity, is endogenously expressed in adipose, and lacks the N-terminal sequence. Both ACC2 isoforms are capable of de novo lipogenesis, suggesting that ACC2, in addition to ACC1, may play a role in lipogenesis. The results demonstrate a significant difference in ACC expression between human and rodents, which may introduce difficulties for the use of rodent models for development of ACC inhibitors.

Show MeSH
Related in: MedlinePlus