When mice don't have enough of a protein called FGF21 during fasting, their livers store more fat because they burn less fat and take in more from the blood — but this doesn't affect how the body overall uses energy.

What we've found so far does not support the idea that FGF21 deficiency increases liver fat in fasting mice by altering fat burning and uptake. Our analysis of the available evidence shows that the claim is refuted by the data. We reviewed 13 assertions related to this question, and all of them contradict the idea that low levels of FGF21 during fasting lead to increased liver fat due to reduced fat burning or higher fat uptake from the blood [1]. While one assertion suggested this mechanism might occur, the body of evidence we analyzed does not support it. Importantly, the evidence indicates that even without sufficient FGF21, fasting mice do not show the expected changes in liver fat accumulation through these specific pathways. We also found no indication that overall energy use is affected, which aligns with some aspects of the proposed mechanism but not the main outcome [1]. Our current analysis shows the evidence leans against this explanation for increased liver fat in FGF21-deficient fasting mice. That doesn’t mean the protein isn’t involved in metabolism — only that, based on what we’ve reviewed so far, this particular link between FGF21 deficiency, fat burning, fat uptake, and liver fat doesn’t hold up. We’re still learning how FGF21 affects metabolism during fasting, and our understanding may change as more studies are published. Right now, the data we have point in a different direction. Practical takeaway: In mice, not having enough FGF21 during fasting doesn’t appear to increase liver fat through the mechanisms described — at least based on the evidence we’ve reviewed so far.