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Inspired by genetic-derived knowledge to design innovative therapeutic tools targeting the adipocyte

Designed stapled peptides targeting specific protein-protein interaction in the adipocyte to restore metabolic fitness

AdipoPharma targets type 2 diabetes, a metabolic disorder characterized by a high level of glucose in blood lasting over a long period known as hyperglycemia. This multifactorial disease combines both the inability of the pancreas β-cells to compensate insulin needs in the organism and insulin resistance in tissues. Hyperglycemia leads to devastating complications such as cardiovascular disease, liver disease, blindness and kidney disease.

About 537 million people worldwide are affected by diabetes according to IDF. The total number is predicted to rise to 643 million by 2030 and to 783 million by 2045. Approximately 6.7 million adults are estimated to have died as a result of diabetes, or its complications in 2021. This disease has entered the top ten causes of death, and is now one of the leading causes of death in the world.

The adipocyte

The (white) adipocyte is a fascinating cell in myriads of ways which has been scientifically neglected for decades usually considered as a mere storing tissue of excess caloric intake. But the adipocyte biology is one of kind with its transiently ciliated status during adipogenesis (Marion et al., PNAS 2009) which will ultimately define the insulin sensitivity of the mature adipose tissue (Marion et al., Cell Metabolism 2012); scientific discoveries made by the study of human rare genetic disorders.

 

Nowadays, the adipocyte and its resident tissue the adipose tissue is recognized as essential for overall metabolic fitness as characterized by its high metabolic and endocrine activities. Although the adipose tissue has garnered high level of scientific attention due to the spiraling out of the obesity pandemic, insulin resistance and type 2 diabetes, there is more than meets the eyes when it comes to the adipocyte best evidenced by the following observations:

  1. The adipose tissue absorbs only 10 % to 15 % of the overall circulating glucose so has traditionally been considered as a minor player in driving type 2 diabetes (See figure).
  2. Obesity considered the main driver of insulin resistance in humans, but on the opposite side of the spectrum, lipodytrophic patients and animal models, a condition where individuals lack adipose tissue, reproduce the exact insulin resistance, type 2 diabetes and related comorbidities clinical traits as the obese patients.


Hence, the adipocyte’s glucose absorption governs whole-body metabolic fitness, thus preventing insulin resistance, type 2 diabetes and the associated deadly complications. Therefore, it is not dependent on the quantity of glucose absorbed but rather on the quality of the downstream products synthesized from the 10 % glucose.

AdipoPharma is harnessing the deep knowledge of the adipocyte biology (Geberhiwot et al., Diabetes 2021) to design and develop a new class of therapeutic agents, termed the Adipeutics, for targeting the adipocyte (Schreyer et al., Diabetes 2022), thereby treating insulin resistance, type 2 diabetes, non-alcoholic fatty liver disease, cardiovascular disorders, fibrosis and other metabolic disorders.

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