MILAN, GABRIELLA, MARNIE GRANZOTTO, ALESSANDRO SCARDA, ALESSANDRA CALCAGNO, CLAUDIO PAGANO, GIOVANNI FEDERSPIL, AND ROBERTO VETTOR. Resistin and adiponectin expression in visceral fat of obese rats: effect of weight loss. Obes Res. 2002;10:1095-1103. Objective: Obesity-related insulin resistance is closely associated with visceral fat accumulation. Several adipocytesecreted molecules have been implicated in the development of type 2 diabetes, among them, the recently discovered adiponectin and resistin proteins. Some of these adipocytokines are also present in the immune system, thus suggesting an intriguing functional connection. Research Methods and Procedures:We determined adiponectin and resistin expressions in visceral (VAT) and subcutaneous adipose tissue of lean and obese Zucker (fa/ fa) rats using reverse-transcription polymerase chain reaction. Moreover, we analyzed the variations after bodyweight reduction in food-restricted obese rats. Results: Resistin and adiponectin expression was significantly lower in VAT of genetically obese in comparison with lean rats; no differences were observed when subcutaneous adipose tissues of the same animals were compared. Weight loss resulted in an increase of adiponectin expression in VAT, whereas a further significant decrease in resistin mRNA level was observed. Resistin is also present and equally expressed in splenocytes of lean and obese rats. Discussion: Adiponectin and resistin are down-regulated in VAT of obese rats. Adiponectin expression is restored to normal levels after body-weight reduction, supporting its link with obesity-related insulin resistance. On the contrary, the further decrease of resistin mRNA after weight loss does not support the hypothesis that resistin may play a causative role in insulin resistance in obese rats. Moreover, we demonstrated the presence of resistin in immunocompetent cells in both humans and rats, thus adding another factor to the list of molecules that adipose tissue shares with the immune system.

Aims/hypothesis: Recent studies suggest that wingless-type MMTV integration site family, member 10B (WNT10B) may play a role in the negative regulation of adipocyte differentiation in vitro and in vivo. In order to determine whether mutations in WNT10B contribute to human obesity, we screened two independent populations of obese subjects for mutations in this gene. Subjects and methods: We studied 96 subjects with severe obesity of early onset (less than 10 years of age) from the UK Genetics of Obesity Study and 115 obese Italian subjects of European origin. Results: One proband with early-onset obesity was found to be heterozygous for a C256Y mutation, which abrogated the ability of WNT10B to activate canonical WNT signalling and block adipogenesis and was not found in 600 control alleles. All relatives of the proband who carried this allele were either overweight or obese. Three other rare missense variants were found in obese probands, but these did not clearly cosegregate with obesity in family studies and one (P301S), which was found in three unrelated subjects with early-onset obesity, had normal functional properties. Conclusions/interpretation: These mutations represent the first naturally occurring missense variants of WNT10B. While the pedigree analysis in the case of C256Y WNT10B does not provide definitive proof of a causal link of this variant with obesity, the finding of a nonfunctioning WNT10B allele in a human family affected by obesity should encourage further study of this gene in other obese populations.

A hypercoagulable state and an increased incidence of thromboembolic complications are reported in Cushing's syndrome. The hypercoagulable state is related to an increase in plasma clotting factors, especially Factor VIII and von Willebrand factor complex, and to an impairment of fibrinolytic capacity. Retrospective analysis of postoperative thromboembolic events in a large group of patients with Cushing's syndrome, including 75 patients (group 1) evaluated in the period from 1972-1981 not receiving anticoagulants, and 232 patients (group 2), evaluated in the period from 1982-2000. Patients of group 1 underwent routine hemostatic function, i.e. prothrombin time and activated partial thromboplastine time. Patients of group 2 underwent a thorough investigation as to hemostatic parameters and received prophylactic treatment with heparin and/or warfarin. Patients with Cushing's syndrome showed various abnormalities of hemostatic parameters. A significant correlation between activated partial thromboplastine time and urinary free cortisol was observed. During follow-up, 15 patients (20%; mean follow-up, 9.4 +/- 6.4 yr) of group 1 and 14 (6.0%; mean follow-up, 6.6 +/- 4.2 yr) of group 2 showed thromboembolic complications. Of these patients, eight of group 1 and one of group 2 died. Survival analysis demonstrated a significantly higher morbidity and mortality due to thromboembolic events in group 1, not receiving anticoagulant prevention, than in group 2, treated with anticoagulants in the perioperative period until cure of the disease and normalization of clotting parameters. Cushing's syndrome is associated with a hypercoagulable state. An adequate anticoagulant prophylaxis can reverse this prothrombotic state and avoid postoperative thromboembolic events.

Treatment with NAC 1200 mg/day improved biological markers and clinical outcomes in patients with COPD exacerbations. It is speculated that the effect of NAC on inflammatory markers may be due to both mucolytic and antioxidant properties.

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