29. Grading and Staging of NAFLD Grading NAFLD 1.Macrovescicular steatosis Grade 0: None Grade 1: Up to 33% Grade 2: 33%-66% Grade 3: >66% 2. Necroinflammatory activity Mild, Mod, Severe Brunt et al Am J Gastro 1999
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32. FFA oxidation Lipogenesis Lipid Export Hepatic Steatosis High Fat/CHO Diet Lack of Exercise Pathogenesis of NASH Insulin Resistance White Adipose Tissue Adipokines- adiponectin Cytokines- TNF IL-6 Oxidative Stress Endotoxin Cytokines ROS Toxins NASH Peroxidation of hepatocyte membrane Cytokine release Stellate cell activation 2 nd Hit
33. FFA oxidation Lipogenesis Lipid Export Hepatic Steatosis High Fat/CHO Diet Lack of Exercise Pathogenesis of NASH CellularFFA Insulin Resistance I B and NF B activation IL6 &TNF α
34. FFA oxidation Lipogenesis Lipid Export Hepatic Steatosis High Fat/CHO Diet Lack of Exercise Pathogenesis of NASH CellularFFA Insulin Resistance GLUT 4 activity Reduced glucose entry into cells
35. FFA oxidation Lipogenesis Lipid Export Hepatic Steatosis High Fat/CHO Diet Lack of Exercise Treatment Strategies In NASH Insulin Resistance White Adipose Tissue Adipokines- adiponectin Cytokines- TNF IL-6 Oxidative Stress Endotoxin Cytokines ROS Toxins NASH Peroxidation of hepatocyte membrane Cytokine release Stellate cell activation 2 nd Hit Diet &Exercise Orlistat Sibutramine Rimonabant Statins Gemfibrozil Metformin Pioglitazone Rosiglitazone Diet &Exercise Probiotics Antioxidants Bariatric Surgery
The next several slides illustrate the histopathology of NAFLD. As mentioned earlier, nonalcoholic fatty liver disease (NAFLD) is a spectrum of hepatic pathology that ranges from fatty liver (steatosis) on the most clinically-benign end of the spectrum to cirrhosis on the opposite extreme where most liver related morbidity and mortality occur. Nonalcoholic steatohepatitis (NASH) is an intermediate form of liver damage that sometimes progresses to cirrhosis. Some individuals who become cirrhotic from NAFLD develop hepatocellular carcinoma.
Changes slowly in days to weeks
Hypothalamic obesity syndrome is incredibly rare. Later, fructose…
Adi Adipose tissue in obesity becomes refracdtory to insulins suppression of fat mobilization., Insulin resistance increases the release of FFA from the adipcyte. In the postprandial period there is an excess of FFA leading to fat deponsition in other tissues Hytperinsulinemiua stimulates fatty acid synthesi while inhibiting the oxidation of fatty acids.,sElevagted insulin may increase the degradation of apolipoprotein B100a component of VLDLcompromising triglyceride transport out of the liver causing anet accumulation of fat. ElevatedFFA and accumulagted triacylglycerol appear to inhibit insulin signalling leading to a reduction in insulin stimulated muscleglucose transporty,.The reduced muscle glucose transport leads to reduced glycogen syntethisisand glycolysis
Another interesting result of this study pertained to gender-related differences in hepatic steatosis. The latter was noted only in the Caucasian population, in which men were almost twice as likely as women to have fatty livers. In other ethnic subgroups, the prevalence of hepatic steatosis was similar in men and women.
