Identification of adipocyte adhesion molecule (ACAM), a novel CTX gene family, implicated in adipocyte maturation and development of obesity

Abstract

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.

A novel role for neural cell adhesion molecule in modulating insulin signaling and adipocyte differentiation of mouse mesenchymal stem cells

“…The second one is terminal differentiation, in which the preadipocytes become mature adipocytes (Rosen and MacDougald, 2006). A previous study suggested that an adipocyte adhesion molecule (ACAM), a 45 kDa protein expressed on adipocytes is involved in adipocyte maturation (Eguchi et al, 2005). In our study, we showed that the adipocyte differentiation in Ncam -/-MSCs is impaired because there was reduced induction of the adipocyte differentiation markers PPARg and P2, and less lipid accumulation.…”

Temporal Dynamics of Tyrosine Phosphorylation in Insulin Signaling

“…These are three membrane-associated guanylate kinases (MPP1, MPP7, and SAP102), members of a family of proteins known to be involved in cell-to-cell adhesion (48), and the adipocyte adhesion protein, a transmembrane protein that has been shown to participate in cell aggregation (49). Thus, it is possible that insulin treatment may alter the adipocyte/adipocyte interactions.…”

Thymosin beta‐4 directs cell fate determination of human mesenchymal stem cells through biophysical effects

“…Also, it is detectable on the plasma membrane of mature adipocytes and facilitates their cell-cell adhesion. 13 In this study, during early adipogenic differentiation of MSCs, ACAM was initially invisible and then gradually detectable on cell membrane (Fig. 6A-D).…”

“…11 Antibodies raised in rabbits against the ACAM were kindly donated for the study by Dr. Jun Wada from Okayama University, Japan. 13 Effects of Tb 4 on In Vitro Differentiation of BM-MSCs Osteogenic, chondrogenic, and adipogenic differentiation of MSCs was induced, as previously described. 14 For all these differentiation studies, 1 mg/mL Tb 4 was added to induction medium once every 3 days along with each medium change.…”