Adipose tissue as a culprit: How obesity leads to diabetes

Researchers surprised: a single enzyme upsets the entire sugar metabolism in a high-fat diet

11-Apr-2023 - Switzerland

A research team at the University of Basel has discovered that a high-fat diet alters the function of adipose tissue, thus impairing its ability to regulate blood sugar. This explains why a high-fat diet poses a significant health risk, particularly for diabetes.

Diabetes is a medical condition in which the body is unable to keep blood sugar in a healthy range. Normally, the pancreas produces sufficient insulin to regulate the blood sugar level and maintain homeostasis. However, in diabetics, the body has lost this ability, leading to hyperglycemia.

Blood sugar levels that are persistently too high can cause long-term damage to blood vessels and lead to severe complications such as blindness or kidney failure. It has been known for some time that obese patients are particularly at risk of developing type 2 diabetes and that adipose tissue plays a critical role in the onset of the disease. In their recent study, researchers led by Professor Michael N. Hall at the Biozentrum, University of Basel, revealed how a high-fat diet triggers diabetes.

A high-fat diet not only leads to an excessive formation of adipose tissue but also impairs this tissue’s ability to regulate blood sugar levels. This is due to an insufficient production of the enzyme hexokinase 2, which normally plays a critical role in the disposal of sugar by adipose tissue. Consequently, the body develops insulin resistance, which means that it cannot efficiently use insulin for the uptake of sugar from the blood into the cells.

Diabetes as a result of enzyme loss

The high-fat diet induced loss of hexokinase 2 leads to reduced sugar disposal in adipose tissue and disturbed sugar metabolism in the liver. The liver produces more sugar than in normal-weight individuals on a healthy diet. The combined effect of these metabolic changes in the two tissues inevitably leads to permanently elevated blood sugar levels and ultimately to diabetes.

"It was absolutely surprising that the loss of a single enzyme specifically in adipose tissue, resulting from a high-fat diet, could have such a profound impact on glucose metabolism of the entire body," says Dr. Mitsugu Shimobayashi, first author of the paper published in eLife. “The far-reaching consequences of these connections never cease to amaze us.” Given the rising prevalence of obesity worldwide, it is important to better understand the mechanisms underlying the development of obesity-related diseases such as diabetes.