When mice don't have a certain protein called FGF21, their liver doesn't turn on some sugar-making genes as much and can't make as much glucose from raw materials after fasting — but their blood sugar still stays normal, probably because other systems step in to help.

What we've found so far is that in mice without the protein FGF21, the liver’s ability to produce glucose during fasting is reduced, but blood sugar levels still remain normal [1]. Our analysis of the available research suggests this happens because the liver doesn’t activate certain sugar-making genes as strongly in the absence of FGF21, which limits glucose production from raw materials like amino acids or glycerol [1]. Even though this metabolic pathway is impaired, the evidence shows that blood sugar stays within a normal range [1]. This suggests that other biological systems may compensate to maintain stable blood sugar levels. We don’t yet know which specific mechanisms are stepping in, but the body appears to have backup processes to help keep glucose regulation functioning even when FGF21 is missing. The evidence we’ve reviewed leans toward FGF21 playing a role in supporting the liver’s glucose production during fasting, but not being the only factor involved in maintaining blood sugar balance [1]. Since all 13.0 supporting assertions point to this same observation and no studies refute it, our current analysis highlights a consistent pattern: glucose output from the liver is reduced without FGF21, yet overall blood sugar control is preserved. Still, this is based on a single line of evidence from mouse studies, and we don’t know how this might apply to humans or what happens under different conditions. Our understanding may change as we review more research over time. Practical takeaway: In mice, missing the FGF21 protein weakens one way the liver makes sugar during fasting, but the body seems to use other methods to keep blood sugar steady.