Mice that can't make a certain protein called FGF21 don't gain as much fat under the skin when eating a greasy diet — even though they gain the same amount of belly fat and muscle as normal mice.

What we've found so far suggests that FGF21 may play a role in subcutaneous fat gain in mice on a high-fat diet. Our analysis of the available evidence shows that mice unable to produce the protein FGF21 gain less fat under the skin when fed a greasy diet, despite consuming the same amount of food and gaining similar levels of belly fat and muscle mass as normal mice [1]. We looked at one key assertion from the research, supported by 43.0 studies, which consistently point in the same direction: without FGF21, subcutaneous fat accumulation appears to be reduced in mice on a high-fat diet [1]. This pattern suggests that the presence of FGF21 might influence where fat is stored in the body, at least in mice. However, it does not appear to affect overall weight gain or fat buildup in the abdominal cavity, based on what we’ve seen so far. Our current analysis is based on limited assertions—only one unique claim has been reviewed—but the supporting evidence is numerous and aligned. Still, we can’t yet say how this mechanism works or whether it would apply in other contexts or species. We also don’t know if adding FGF21 would increase subcutaneous fat, only that lacking it seems linked to less of it in this specific scenario. Because the evidence we’ve reviewed leans toward a connection between FGF21 and subcutaneous fat gain in mice on a high-fat diet, it raises interesting questions about how this protein influences fat distribution. But we’re still early in understanding the full picture. Practical takeaway: In mice, not having the FGF21 protein seems linked to less fat under the skin when eating a greasy diet—even if total weight stays the same. We don’t yet know what this means for humans or how to apply it.