Biochem. J. (2005) 387
(343–353) (Printed in Great Britain)
Identification of adipocyte adhesion molecule (ACAM), a novel CTX gene family, implicated in adipocyte maturation and development of obesity
Jun EGUCHI*, Jun WADA*1, Kazuyuki HIDA*, Hong ZHANG*†, Takashi MATSUOKA*, Masako BABA*, Izumi HASHIMOTO*, Kenichi SHIKATA*, Norio OGAWA‡ and Hirofumi MAKINO*
*Department of Medicine and Clinical Science, Okayama University Graduate School of Medicine and Dentistry, 2-5-1 Shikata-cho, Okayama 700-8558, Japan, †Institute of Nephrology, the First Teaching Hospital, Beijing Medical University, 8 Xi Shi Ku Street, Beijing 100034, People's Republic of China, and ‡Department of Brain Science, Okayama University Graduate School of Medicine and Dentistry, 2-5-1 Shikata-cho, Okayama 700-8558, Japan
Few cell adhesion molecules have been reported to be expressed in mature adipocytes, and the significance of cell adhesion process in adipocyte biology is also unknown. In the present study, we identified ACAM (adipocyte adhesion molecule), a novel homologue of the CTX (cortical thymocyte marker in Xenopus) gene family. ACAM cDNA was isolated during PCR-based cDNA subtraction, and its mRNA was shown to be up-regulated in WATs (white adipose tissues) of OLETF (Otsuka Long–Evans Tokushima fatty) rats, an animal model for Type II diabetes and obesity. ACAM, 372 amino acids in total, has a signal peptide, V-type (variable) and C2-type (constant) Ig domains, a single transmembrane segment and a cytoplasmic tail. The amino acid sequence in rat is highly homologous to mouse (94%) and human (87%). ACAM mRNA was predominantly expressed in WATs in OLETF rats, and increased with the development of obesity until 30 weeks of age, which is when the peak of body mass is reached. Western blot analysis revealed that ACAM protein, approx. 45 kDa, was associated with plasma membrane fractions of mature adipocytes isolated from mesenteric and subdermal adipose deposits of OLETF rats. Up-regulation of ACAM mRNAs in obesity was also shown in WATs of genetically obese db/db mice, diet-induced obese ICR mice and human obese subjects. In primary cultured mouse and human adipocytes, ACAM mRNA expression was progressively up-regulated during differentiation. Several stably transfected Chinese-hamster ovary K1 cell lines were established, and the quantification of ACAM mRNA and cell aggregation assay revealed that the degree of homophilic aggregation correlated well with ACAM mRNA expression. In summary, ACAM may be the critical adhesion molecule in adipocyte differentiation and development of obesity.
Key words: adipose tissue, adhesion molecule, cell aggregation, CTX gene family, obesity.
Abbreviations used: ACAM, adipocyte adhesion molecule; BMI, body mass index; BT-IgSF, brain- and testis-specific Ig superfamily; CAR, coxsackievirus and adenovirus receptor; CHO, Chinese-hamster ovary; CLMP, CAR-like membrane protein; CTX, cortical thymocyte marker in Xenopus; CTXL, CTX-like; C-type domain, constant domain; DIO, diet-induced obesity; DMEM, Dulbecco's modified Eagle's medium; ESAM, endothelial cell-selective adhesion molecule; GPA33, glycoprotein A33; HBSS, Hanks balanced salt solution; HDM, high-density microsome; JAM, junctional adhesion molecule; LDM, low-density microsome; LETO, Long–Evans Tokushima Otsuka; OLETF, Otsuka Long–Evans Tokushima fatty; PPARg, peroxisome-proliferator-activated receptor-g; RACE, rapid amplification of cDNA ends; TZD, thiazolidinedione; V-type domain, variable domain; WAT, white adipose tissue.
1To whom correspondence should be addressed (email junwada@md.okayama-u.ac.jp).
The nucleotide sequence data reported will appear in DDBJ, EMBL, GenBank® and GSDB Nucleotide Sequence Databases under the accession numbers AF302047 (rat ACAM), AY326421 (mouse ACAM) and AF326422 (human ACAM).
Received 8 October 2004/22 November 2004; accepted 24 November 2004
Published as BJ Immediate Publication 24 November 2004, DOI 10.1042/BJ20041709
The Biochemical Society, London ©2005
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