From the Research
The expected outcome in the fed state when an experimental drug inhibits GLUT-4 translocation in adipocytes is reduced glycerol-3-phosphate production (option B). GLUT-4 transporters are insulin-responsive glucose transporters that normally move from intracellular vesicles to the cell membrane during the fed state when insulin levels are high. This translocation allows glucose to enter adipocytes where it can be metabolized. When GLUT-4 translocation is inhibited, glucose uptake into adipocytes decreases significantly. Without adequate glucose entry, the production of glycerol-3-phosphate is reduced since it is primarily derived from glucose metabolism through glycolysis and subsequent conversion of dihydroxyacetone phosphate, as shown in a study published in 2021 1. Glycerol-3-phosphate is essential for triglyceride synthesis as it forms the backbone to which fatty acids attach. With reduced glycerol-3-phosphate availability, triglyceride synthesis would decrease rather than increase, making option D incorrect. The drug would not directly affect fatty acid uptake (option A), and hormone-sensitive lipase would not be activated in the fed state when insulin levels are high (option C), as insulin suppresses lipolysis. Additionally, a study from 2008 found that glyceroneogenesis is the dominant pathway for triglyceride glycerol synthesis in vivo in the rat 2, but this does not change the fact that inhibiting GLUT-4 translocation would reduce glycerol-3-phosphate production. Other studies have also shown the importance of glycerol-3-phosphate in triglyceride synthesis, such as the study published in 2010 that found GPAT3 and GPAT4 are regulated by insulin-stimulated phosphorylation and play distinct roles in adipogenesis 3. However, the most recent and highest quality study relevant to this question is the one published in 2021, which supports the conclusion that inhibiting GLUT-4 translocation would reduce glycerol-3-phosphate production 1. Therefore, the expected outcome in the fed state when an experimental drug inhibits GLUT-4 translocation in adipocytes is reduced glycerol-3-phosphate production. Some key points to consider are:
- GLUT-4 translocation is essential for glucose uptake in adipocytes
- Glycerol-3-phosphate production is reduced when glucose uptake is decreased
- Triglyceride synthesis is decreased when glycerol-3-phosphate availability is reduced
- The drug would not directly affect fatty acid uptake or hormone-sensitive lipase activity in the fed state.