Obesity, Type 2 Diabetes, NASH

Overweight and obesity have increased significantly during the last decades and, according to the WHO, have become a “global epidemic”. Worldwide, the number of overweight or obese adults almost tripled, in the age group of 5-19 years the prevalence has increased tenfold in the last 40 years. Today, almost every third person on earth is overweight and obesity is regarded as the main cause for lipometabolism disorders, fatty liver, diabetes, hypertension, stroke and certain cancers.

Disturbances in lipid metabolism can cause fat deposition in the liver. Almost every third adult in the industrial countries suffers from non-alcoholic fatty liver, associated with an increased risk for complications like liver cirrhosis, hepatic cancer, type 2 diabetes, heart attack or stroke. As a consequence of the continuous fat deposition, the liver can get inflamed, this is called non-alcoholic steatohepatitis or NASH.

The predisposition for type 2 diabetes is genetically determined, but for overweight and obese people the risk for getting the disease can increase by a factor up to 30, depending on the severity of the overweight. The oversupply of sugar (glucose) in the blood and the permanently elevated level of insulin lead to a decrease in the sensitivity and number of insulin receptors. The insulin released then is not sufficient to control the blood sugar level. Accordingly, the body then aims to compensate for this deficiency by producing more insulin in the beta cells of the pancreas, which in turn leads to overstress and exhaustion of the pancreas and finally to the formation of type 2 diabetes.

With more than 90% of cases diabetes type 2 is nowadays the most common form of diabetes. Whereas previously considered as “adult-onset diabetes”, in recent years it is becoming also more frequent in younger people and even children.

Several studies have shown that in the case of obesity the formation of a certain class of lipids, the so-called ceramides, is enhanced. In the body, ceramides are synthesized by ceramide synthases, which are also overexpressed in the case of obesity. In mice, it was shown that inhibiting ceramide production protected the animals from insulin resistance. However, blocking ceramide production completely led to severe side effects, for example in the development of the mice.

But, if only a certain ceramide synthase, ceramide synthase 6 (CerS), is blocked, a positive effect resulted: although the mice were continued on a high-fat diet, they lost weight. The inhibition of CerS also protected mice from developing insulin resistance and type 2 diabetes and the formation of a fatty liver and NASH.

As the lipid metabolism of mouse and human is comparable with regard to ceramides, an inhibition or downregulation of CerS6 should also lead to an improvement in humans concerning obesity, NASH, insulin resistance and type 2 diabetes.

With the help of UgimersTM, the amount of CerS6 can be downregulated to a normal, healthy level.