Classically, the non-alcoholic fatty liver disease(NAFLD) physiopathology and progression has been summarized in the two hits hypothesis. The first hit is represented by the action of hyperinsulinemia and insulin resi...Classically, the non-alcoholic fatty liver disease(NAFLD) physiopathology and progression has been summarized in the two hits hypothesis. The first hit is represented by the action of hyperinsulinemia and insulin resistance, accompanying obesity, that leads to liver steatosis increasing the absolute non esterified fatty acids uptake in the liver and the esterification to form triacylglycerol. The oxidative stress is involved in the second hit leading to the progression to nonalcoholic steatohepatitis(NASH) because of its harmful action on steatosic hepatocytes. However, at the present time, the two hits hypothesis needs to be updated because of the discover of genetic polymorphisms involved both in the liver fat accumulation and progression to NASH that make more intriguing understanding the NAFLD pathophysiological mechanisms. In this editorial, we want to underline the role of PNPLA3 I148 M, GPR120 R270 H and TM6SF2 E167 K in the pediatric NAFLD development because they add new pieces to the comprehension of the NAFLD pathophysiological puzzle. The PNPLA3 I148 M polymorphism encodes for an abnormal protein which predisposes to intrahepatic triglycerides accumulation both for a loss-of-function of its triglyceride hydrolase activity and for a gain-of-function of its lipogenic activity.Therefore, it is involved in the first hit, such as TM6SF2 E167 K polymorphisms that lead to intrahepatic fat accumulation through a reduced very low density lipoprotein secretion. On the other hand, the GPR120 R270 H variant, reducing the anti-inflammatory action of the GPR120 receptor expressed by Kuppfer cells, is involved in the second hit leading to the liver injury.展开更多
AIM:To verify if subclinical hypothyroidism(SCH) could be associated to atopy in children.METHODS:Seven hundred and thirty-two Caucasian children from South Italy presenting symptoms of allergic disease were enrolled ...AIM:To verify if subclinical hypothyroidism(SCH) could be associated to atopy in children.METHODS:Seven hundred and thirty-two Caucasian children from South Italy presenting symptoms of allergic disease were enrolled and submitted to atopy,obesity,chronic low grade inflammation,and SCH work up.RESULTS:Four hundred and forty-five out of 705(63.12%) children affected by allergic disease were diagnosed as atopic and 260(36.88%) as not atopic.The SCH prevalence was 6.3%.Significant higher prevalence of SCH among atopic children with average(group 2) and high(group 3) low grade chronic inflammation compared to atopic children with mild(group 1)low grade chronic inflammation was present.Moreover,group 1 and group 2 presented an OR to show SCH of2.57(95%CI:1.55-6.26) and 2.96(95%CI:1.01-8.65),respectively.Both in atopic and not atopic children we found C3 serum levels significantly higher in group 3respect to group 2 and group 1.Noteworthy,among atopic patients,also total immunoglobulin E(IgE) serum levels,were significantly higher in group 3 compared to group 2 and group 1 children.In atopic children,C3 and total IgE serum values increased in parallel with the increase of C-reactive protein values,while in not atopic children this phenomenon was not evident.CONCLUSION:The possibility exists that an increasing atopic inflammation contributes to SCH occurrence.So far this is the first report in literature showing an association between SCH and atopy but further studies are needed to confirm our data.展开更多
文摘Classically, the non-alcoholic fatty liver disease(NAFLD) physiopathology and progression has been summarized in the two hits hypothesis. The first hit is represented by the action of hyperinsulinemia and insulin resistance, accompanying obesity, that leads to liver steatosis increasing the absolute non esterified fatty acids uptake in the liver and the esterification to form triacylglycerol. The oxidative stress is involved in the second hit leading to the progression to nonalcoholic steatohepatitis(NASH) because of its harmful action on steatosic hepatocytes. However, at the present time, the two hits hypothesis needs to be updated because of the discover of genetic polymorphisms involved both in the liver fat accumulation and progression to NASH that make more intriguing understanding the NAFLD pathophysiological mechanisms. In this editorial, we want to underline the role of PNPLA3 I148 M, GPR120 R270 H and TM6SF2 E167 K in the pediatric NAFLD development because they add new pieces to the comprehension of the NAFLD pathophysiological puzzle. The PNPLA3 I148 M polymorphism encodes for an abnormal protein which predisposes to intrahepatic triglycerides accumulation both for a loss-of-function of its triglyceride hydrolase activity and for a gain-of-function of its lipogenic activity.Therefore, it is involved in the first hit, such as TM6SF2 E167 K polymorphisms that lead to intrahepatic fat accumulation through a reduced very low density lipoprotein secretion. On the other hand, the GPR120 R270 H variant, reducing the anti-inflammatory action of the GPR120 receptor expressed by Kuppfer cells, is involved in the second hit leading to the liver injury.
文摘AIM:To verify if subclinical hypothyroidism(SCH) could be associated to atopy in children.METHODS:Seven hundred and thirty-two Caucasian children from South Italy presenting symptoms of allergic disease were enrolled and submitted to atopy,obesity,chronic low grade inflammation,and SCH work up.RESULTS:Four hundred and forty-five out of 705(63.12%) children affected by allergic disease were diagnosed as atopic and 260(36.88%) as not atopic.The SCH prevalence was 6.3%.Significant higher prevalence of SCH among atopic children with average(group 2) and high(group 3) low grade chronic inflammation compared to atopic children with mild(group 1)low grade chronic inflammation was present.Moreover,group 1 and group 2 presented an OR to show SCH of2.57(95%CI:1.55-6.26) and 2.96(95%CI:1.01-8.65),respectively.Both in atopic and not atopic children we found C3 serum levels significantly higher in group 3respect to group 2 and group 1.Noteworthy,among atopic patients,also total immunoglobulin E(IgE) serum levels,were significantly higher in group 3 compared to group 2 and group 1 children.In atopic children,C3 and total IgE serum values increased in parallel with the increase of C-reactive protein values,while in not atopic children this phenomenon was not evident.CONCLUSION:The possibility exists that an increasing atopic inflammation contributes to SCH occurrence.So far this is the first report in literature showing an association between SCH and atopy but further studies are needed to confirm our data.
