Alterations in adipocytokines and cGMP homeostasis in morbid obesity patients reverse after bariatric surgery.

OBJECTIVE: Obesity-associated nonalcoholic fatty liver disease (NAFLD), covering from simple steatosis to nonalcoholic steatohepatitis (NASH), is a common cause of chronic liver disease. Aberrant production of adipocytokines seems to play a main role in most obesity-associated disorders. Changes in adipocytokines in obesity could be mediated by alterations in cyclic GMP (cGMP) homeostasis. The aims of this work were: (1) to study the role of altered cGMP homeostasis in altered adipocytokines in morbid obesity, (2) to assess whether these alterations are different in simple steatosis or NASH, and (3) to assess whether these changes reverse in obese patients after bariatric surgery. DESIGN AND METHODS: In 47 patients with morbid obesity and 45 control subjects, the levels in blood of adipocytokines, cGMP, nitric oxide (NO) metabolites, and atrial natriuretic peptide (ANP) were studied. Whether weight loss after a bariatric surgery reverses the changes in these parameters was evaluated. RESULTS: NO metabolites and leptin increase (and adiponectin decreases) similarly in patients with steatosis or NASH, suggesting that these changes are due to morbid obesity and not to liver disease. Inflammation and cGMP homeostasis are affected both by morbid obesity and by liver disease. The increases in interleukin 6 (IL-6), interleukin 18 (IL-18), plasma cGMP, ANP, and the decrease in cGMP in lymphocytes are stronger in patients with NASH than with steatosis. All these changes reverse completely after bariatric surgery and weight loss, except IL-18. CONCLUSION: Altered cGMP homeostasis seems to contribute more than inflammation to changes in leptin and adiponectin in morbid obesity.

Contribution of hyperammonemia and inflammatory factors to cognitive impairment in minimal hepatic encephalopathy.

To assess the contribution of hyperammonemia and inflammation to induction of mild cognitive impairment (or MHE). We analyzed the presence of mild cognitive impairment (CI) by using the PHES battery of psychometric tests and measured the levels of ammonia and of the inflammatory cytokines IL-6 and IL-18 in blood of patients with different types of liver or dermatological diseases resulting in different grades of hyperammonemia and/or inflammation. The study included patients with 1) liver cirrhosis, showing hyperammonemia and inflammation; 2) non-alcoholic fatty liver disease (NAFLD) showing inflammation but not hyperammonemia; 3) non-alcoholic steatohepatitis (NASH) showing inflammation and very mild hyperammonemia; 4) psoriasis, showing inflammation but not hyperammonemia; 5) keloids, showing both inflammation and hyperammonemia and 6) controls without inflammation or hyperammonemia. The data reported show that in patients with liver diseases, cognitive impairment may appear before progression to cirrhosis if hyperammonemia and inflammation are high enough. Five out of 11 patients with NASH, without liver cirrhosis, showed cognitive impairment associated with hyperammonemia and inflammation. Patients with keloids showed cognitive impairment associated with hyperammonemia and inflammation, in the absence of liver disease. Hyperammonemia or inflammation alone did not induce CI but the combination of certain levels of hyperammonemia and inflammation is enough to induce CI, even without liver disease.