Nck2, an unexpected regulator of adipogenesis.

The regulation of adipose tissue expansion by adipocyte hypertrophy and/or hyperplasia is the topic of extensive investigations given the potential differential contribution of the 2 processes to the development of numerous chronic diseases associated with obesity. We recently discovered that the loss-of-function of the Src homology domain-containing protein Nck2 in mice promotes adiposity accompanied with adipocyte hypertrophy and impaired function, and enhanced adipocyte differentiation in vitro. Moreover, in severely-obese human's adipose tissue, we found that Nck2 expression is markedly downregulated. In this commentary, our goal is to expand upon additional findings providing further evidence for a unique Nck2-dependent mechanism regulating adipogenesis. We propose that Nck2 should be further investigated as a regulator of the reliance of white adipose tissue on hyperplasia versus hypertrophy during adipose tissue expansion, and hence, as a potential novel molecular target in obesity.

Co-encapsulation of bioengineered IGF-II-producing cells and pancreatic islets: effect on beta-cell survival.

Insulin-like growth factor-II (IGF-II) has been shown to promote pancreatic ß-cell survival. We evaluated the effect of co-encapsulating islets and bioengineered IGF-II-producing cells on islet cell survival. IGF-II or green fast protein (GFP) genes were transferred into TM4 cells, and purified using a neomycin resistance gene, leading to pure cell cultures (TM4-IGF-II or TM4-GFP) with a stable overexpression of the transferred gene. Islets were co-encapsulated with TM4-IGF-II or TM4-GFP, or encapsulated alone in alginate microcapsules. Rat and mouse islet cell survival was studied in vitro and in vivo, respectively. After 12 days in culture, islet viability (dual staining, acridine orange/propidium iodide) was 83% with TM4-IGF-II, compared with 51% (P<0.05) and 41% (P<0.001) with TM4-GFP and islets alone, respectively. The study of islet necrotic centers and the evaluation of islet function, using the MTS (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt) assay, yielded similar results. From 125 days after transplantation, more diabetic mice maintained normoglycemia when they were transplanted with islets co-encapsulated with TM4-IGF-II (4/7). A significant difference for the maintenance of normoglycemia was observed between recipients of islets co-encapsulated with TM4-IGF-II versus islets alone (P=0.023), or with TM4-GFP (P=0.048). In conclusion, the co-encapsulation of islets with bioengineered IGF-II-producing cells promotes islet cell survival.

Biocompatibility and physicochemical characteristics of alginate-polycation microcapsules.

There is a need for better understanding of the biocompatibility of alginate-polycation microcapsules based on their physicochemical characteristics. Microcapsules composed of alginate with 44% (IntG) or 71% (HiG) guluronate, gelled with calcium (Ca) or barium (Ba) and coated with poly-L-lysine (PLL) or poly-l-ornithine (PLO), followed by IntG alginate were compared. For microcapsules with an IntG(Ca) gel core, using PLO instead of PLL resulted in less immune cell adhesion after 2 days in C57BL/6J mice. The PLO microcapsules were also characterized by greater hydrophilicity and superior resistance to swelling and damage under osmotic stress. For microcapsules with a PLL membrane, replacing the IntG(Ca) gel core with IntG(Ba) or HiG(Ca) gel resulted in stronger immune responses (p<0.05). This was explained by poor penetration of PLL into the gel, as demonstrated by Fourier transform infrared spectroscopy analyses and membrane rupturing during osmotic swelling. X-ray photoelectron spectroscopy analyses show that all microcapsules had the same amount of polycation at their surface. Moreover, alginate coatings had non-significant effects on the biocompatibility and physicochemical properties of the microcapsules. Thus, alginate-polycation interactions for membrane formation are more important for biocompatibility than either the quantity of polycation at the surface or the alginate coating.