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NASH or “diabesity*”: which comes first?

Recent perspective on an “egg or chicken paradigm”

*Contraction of diabetes and obesity

It’s safe to say that the egg came first because if there had been no egg, there would have been no chicken. Let’s discover the scientific reality of NASH.

The liver plays a central role in MetS, a cluster of metabolic conditions that increase the risk of heart disease, stroke, type 2 diabetes, and other chronic diseases. The pathophysiology of NAFLD/NASH is linked to adipose tissue dysfunction and insulin resistance, but it also depends on liver vulnerability and repair mechanisms.

The affected population is by nature quite heterogeneous; some people are very obese but have little steatohepatitis and fibrosis, while others are only slightly overweight but develop significant hepatic lesions.

Early disease improves with amelioration of the metabolic drivers of disease. However, in more advanced disease stages, intrahepatic changes are more profound (e.g., vascular alterations, fibrosis). Recent data showed that metabolically active drugs without direct intrahepatic effects did not regress fibrosis.

Therefore, treatment of stages with more advanced intrahepatic lesions likely requires additional (intrahepatic) pathways to be tackled.
The substantial burden of liver disease in metabolic syndrome (MetS) is not tackled by simply improving body weight. The liver in NAFLD/MASLD* contributes to metabolic derangements, such as an increased risk of incident diabetes in people who are not yet diabetic and more difficult control of diabetes in people with NAFLD/MASLD*.

NAFLD/NASH also contributes to the development of cardiovascular diseases (CVD).

Therefore, the liver is a central organ in MetS and a driver of the progression of morbidities associated with MetS.
Drugs that impact NASH could potentially benefit MetS and CVD. This is because NASH is a major contributor to the metabolic and cardiovascular complications of MetS.

.*New definition for NAFLD.