Arun Sanyal, MD, on Treatment Approaches to Targeting Metabolic Pathways in NAFLD

In this video, Arun Sanyal, MD, talks about how and why metabolic pathways are targeted when treating nonalcoholic fatty liver disease. He recently spoke about this topic at the 21st Annual Harvard Nutrition and Obesity Symposium on NAFLD.

Arun Sanyal, MD, is a professor of medicine at Virginia Commonwealth University in Richmond, Virginia.


Hello, my name is Arun Sanyal, and I'm a professor of medicine at Virginia Commonwealth University.

The obvious and the most-simple way is to attack it with lifestyle intervention with the goal of reducing excess adipose tissue and reducing body weight. It is important to remember that weight loss covers a lot of information. Weight loss is beneficial when you lose access adipose tissue while retaining your muscle mass.

Many of our patients not only have excess adipose tissue but also have sarcopenia, which is a bad combination because it exacerbates multiple other end-organ problems.

So, simple weight loss measures are the simplest way to target this. There's of course bariatric surgery, but that has its own set of problems.

Then there are other approaches that target the adipose tissue itself, such as the use of causality end ions that reduce lipolysis in adipose tissue and the release of fatty acids that then can be delivered to the liver and produce lipotoxic stress in the liver.

There are other approaches that are more liver-targeted, which attack the de novo lipogenesis pathway, which reduces the ability of the liver to synthesize fat. It is really interesting that in NASH, not only is there excess fat being delivered to the liver, but the liver’s intrinsic capacity to make fat is also enhanced.

So you get a double whammy—one from the excess fat log from the periphery and second big conversion of excess carbohydrates into fat in the liver. So, both approaches are currently being used.

Finally, one can reduce the metabolic load by increasing the utilization of fat within the liver. And some examples of that are the use of caroxin β receptors, etc, and [indecipherable] alphas in various combinations for that purpose.

Finally, there are integrated approaches. So, it's very interesting that the GLP-1 receptor agonists, which do not have receptors in the liver, are beneficial for weight loss and recently have been shown to also improve steatohepatitis.

And so, GLP-1 targets both the adipose tissue and muscle, and can improve insulin sensitivity. Some of its effects are central by reducing appetite and causing weight loss.

Another class of drugs that is increasingly being studied are the SGLP-2 inhibitors, which also break the metabolic inflexibility within the muscle and allow increased fat to be utilized for energy, because it drains glucose from the body and forces tissues to burn fat.

The GLP-1 and the SGLP-2 classes of drugs are of particular relevance also because they have been shown in type 2 diabetes with high-risk features for cardiovascular disease to produce all-cause mortality benefit as well as reduction in cardiovascular events and stabilization of kidney disease.

Thank you everyone for listening to me today. I hope you enjoyed my presentation.