What is GLP-1?
GLP-1 stands for glucagon-like peptide-1, a hormone that regulates glucose and its metabolism. It is produced and secreted from the endocrine cells in the intestine after food intake [1].
Among the key functions of this peptide are the regulation of insulin and glucagon secretion, appetite, and gastric emptying [2].
However, GLP-1 also influences lipid metabolism. It inhibits fat synthesis, increases cholesterol metabolism, and aids far differentiation and browning of adipocytes [3].
When secreted, GLP-1 has a strong glucose-level-lowering effect, which makes its synthetic version an alternative treatment for type 2 diabetes [4]. The natural version is not suited for therapeutic use as it undergoes rapid metabolism in the circulation [2].
How does GLP-1 affect the adipocytes?
GLP-1 affects adipocyte functions like lipid metabolism, glucose uptake, and adipogenesis.
It increases glucose uptake in adipocytes by increasing the translocation of glucose transporter type 4 to the plasma membrane, which improves the glucose resistance levels in adipocytes [5].
Additionally, GLP-1 enhances the effect of insulin on the adipocytes and promotes fatty synthesis in the adipocytes [6].
GLP1 regulates lipid metabolism on the genetic level. The hormone inhibits the expression of the adipose triglyceride lipase, an enzyme responsible for breaking down fat storage [5]. Also, GLP-1 increases the activity of genes responsible for fat production [7].
Moreover, GLP-1 promotes the creation of new fat cells at the preadipocyte differentiation level. It also lowers the fat tissue's inflammatory process and macrophage infiltration.
What happens to the adipocytes in the bone marrow?
GLP-1 influences all adipocytes, including the ones in the bone marrow. One of its effects is the promotion of the proliferation of human bone marrow-derived mesenchymal stem cells.
However, it suppresses the differentiation of these stem cells into adipocytes, leading to a reduction in the fat cell count in the marrow [10, 11].
It does so by lowering the expression of adipocyte markers like lipoprotein lipase, adipocyte protein 2, and peroxisome proliferator activated receptor gamma [12].
Furthermore, GLP-1 promotes the development of osteoblasts from adipose-derived stem cells, stopping their progression into fat cells [12].
GLP-1's promotion of bone-creating cells and inhibition of adipocyte differentiation make it an important regulator of bone marrow balance.
How does GLP-1 affect the bone?
Due to its influence on cell differentiation and the resulting promotion of bone formation, GLP-1 increases bone density and quality [13]. The positive effect can be observed in the rise of a key bone health indicator, the trabecular bone mass [14].
These effects theoretically should also occur when the bone is exposed to synthetic GLP-1-mimicking substances [15]. Among them are medications such as
- Exenatide and liraglutide [16],
- Dulaglutide [17],
- Semaglutide [18], like Ozempic or Rybelsus.
However, the positive effect of these drugs on the bones is not entirely confirmed. Some studies indicate that the synthetic GLP-1 mimicking medication does not significantly affect bone density and formation markers [19]. Also, clinically, the use of such medication does not lower the risk of fractures compared to other diabetic drugs [20].
More research is needed to understand why GLP-1-like drugs do not achieve the same effect as natural hormones.