PKA regulatory subunit R2B is required for murine and human adipocyte differentiation

ADIPOGENESIS IS A COMPLEX PROCESS MODULATED BY SEVERAL FACTORS, INCLUDING CAMP SIGNALING. THE MAIN CAMP TARGET IS PROTEIN KINASE A (PKA), A TETRAMERIC ENZYME WITH FOUR REGULATORY SUBUNITS SHOWING TISSUE-SPECIFIC EXPRESSION AND FUNCTION: PRKAR2B is the main regulatory subunit in adipose tissue in mice and in adult humans. This study aimed to evaluate the expression of PKA regulatory subunits in human adipose tissue during fetal development and to investigate their role in the differentiation of 3T3-L1 and primary human preadipocytes. The expression of PKA regulatory subunits was evaluated in fetal adipose tissue (immunohistochemistry) and in cultured 3T3-L1 and primary human preadipocytes (western blot analysis). Cultured cells were transiently transfected with siRNA against PRKAR2B and induced to differentiate. Differentiation was evaluated by intracellular triglyceride staining (Oil Red O) and expression of molecular markers of adipocyte differentiation. In this study, we found that PRKAR2B is the main regulatory subunit in human adipose tissue during fetal development, from 12 weeks of gestation to the end of gestation, as well as in 3T3-L1 and primary human preadipocytes. The expression of PRKAR2B increases progressively during in vitro differentiation. The silencing of PRKAR2B abolishes the increase in the expression of peroxisome proliferator-activated receptor gamma (PPAR\u3b3 (PPARG)), fatty acid synthase, aP2 (FABP4), and lipoprotein lipase, as well as intracellular triglyceride accumulation, resulting in impaired adipocyte differentiation in both mouse and human cell systems. In conclusion, PRKAR2B is the key PKA regulatory subunit involved in mouse and human adipose tissue development. The physiological increase in the expression of PRKAR2B is an essential event in adipogenesis in both mice and humans, and it might represent a possible target for future strategies for obesity treatment

Obesit\ue0: epidemiologia ed impatto sociale

L\u2019obesit\ue0 ha attualmente raggiunto proporzioni epidemiche in tutti i continenti (globesity), i tassi di incidenza sono in rapida crescita e i soggetti affetti da sovrappeso ed obesit\ue0 raggiungono in alcuni paesi oltre il 60% della popolazione adulta. Si pu\uf2 stimare con ragionevole approssimazione che in Italia vi siano 500.000 grandi obesi (BMI > 40) e 4.700.000 obesi con BMI compreso tra 30 e 40 kg/m2. Tutte le indagini epidemiologiche concordano nell\u2019indicare che il sovrappeso e l\u2019obesit\ue0 incrementano in modo significativo la morbilit\ue0 e la mortalit\ue0. Vi sono alcune malattie per le quali \ue8 stato ampiamente dimostrato uno stretto rapporto con l\u2019obesit\ue0 e tra queste le pi\uf9 importanti sono: diabete, dislipidemie, vasculopatie, ipertensione, cardiopatie, artropatie e pneumopatie. Gli autori valutano in termini economici l\u2019elevata spesa sociosanitaria connessa al trattamento dell\u2019obesit\ue0 e delle patologie ad essa correlate. Facendo riferimento a diversi studi, mostrano come l\u2019utilizzo della chirurgia bariatrica pu\uf2 soddisfare da un lato l\u2019esigenza medica di riportare il soggetto obeso a valori ponderali accettabili, migliorando quindi la sua qualit\ue0 di vita, dall\u2019altro a garantire nel tempo il miglioramento delle patologie obesit\ue0-correlate, determinando un contenimento della spesa sanitaria che esse producono. La valutazione dei dati relativi ai costi degli interventi chirurgici bariatrici spinge gli autori a richiedere una rivalutazione delle tariffe dei DRG ed una maggiore attenzione delle istituzioni nei confronti della chirurgia bariatrica, sino ad ora considerata una \u201cnicchia\u201d iperspecialistica

Incidence of venous thromboembolism in laparoscopic bariatric surgery : preliminary report

Background: Laparoscopic bariatric surgery, due to short operative duration and early ambulation of the patients, has reduced the incidence of postoperative venous thromboembolism (VTE) in morbidly obese patients.We evaluated the incidence of VTE in laparoscopic gastric banding for morbid obesity, and determined the optimal duration of heparin prophylaxis comparing two different regimens of low molecular weight heparin (LMWH). Methods: Since December 2002, two groups of patients, both males and females, underwent laparoscopic gastric banding for morbid obesity. Both groups were treated with LMWH 4,000 U/day, for different periods of time. Group A (49 patients, mean age: 38 years, mean BMI: 41.8) was treated until hospital discharge (3-4 days). Group B (38 patients, mean age: 37 years,, mean BMI 42.3) was treated for 10 days postoperatively. All patients wore elastic compression stockings and were early ambulant. The incidence of VTE was assessed by means of a standardized Color Doppler, performed before the operation, at the 3rd and 10th postoperative day, and a clinical check after 1 and 3 months. Results: Neither deep vein thrombosis nor pulmonary embolism were observed in either groups. In Group A, after suspension of LMWH, superficial thrombophlebitis occurred in 2 patients, who had saphenous reflux, which required readministration of LMWH. Conclusion: This preliminary report shows that the incidence of venous thromboembolism is low in laparoscopic gastric banding. The occurence of 2 superficial thromboses suggests, however, the need for a longer heparin prophylaxi