Nonalcoholic fatty liver disease (NAFLD) affects one fourth of the world’s population. It is the most common form of liver disease. NAFLD ranges from nonalcoholic fatty liver (NAFL) to nonalcoholic fatty hepatitis (non-alcoholic steatohepatitis NASH), which sometimes leads to cirrhosis and cancer of the liver (hepatocellular carcinoma (HCC). These diseases are a major cause of liver transplant and death from cirrhosis and they are rapidly increasing.
This post and the links will provide a great opportunity for you learn how extra abdominal fat leads to organ damage, organ inflammation. death of functional cells, growth of scar tissue, and ultimately cancer formation. This process is not limited to the liver, but also impacts the kidney, lung, and other organs. As usual, switching on the master metabolic switch mTOR and switching off AMPK is central in these processes. Medications that switch off mTOR and switch on AMPK are beneficial and protect cells and organs.
Calorie restriction, intermittent fasting, and exercise switch off mTOR and switch on AMPK. SGLT2 inhibitors like empagliflozin switch on AMPK directly. Metformin switches off mTOR and switches on AMPK. Diet, exercise, and metformin for prediabetes and diabetes should be beneficial. Empagliflozin can be added if sugar is not well controlled with those measures. Overeating and high insulin levels have the opposite effect because they switch on mTOR and switch off AMPK. In the management of prediabetes and type 2 diabetes we should focus on interventions that favor weight loss while switching off mTOR and switching on AMPK. All of the green box medications in the diagram push in that direction.
Clinical trials are short. Many of the trials looking at drug effects only last weeks. These diseases last for decades. Comparing impacts on liver disease in patients on optimal medical therapy vs usual care using big data should help us understand the impact of these treatments. Let’s get started.
Yes. Please add ketogenic eating and intermittent fasting to these green buttons. Thank you.