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].
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.