Inulin Increases Lean Mass and Improves HOMA-IR in Mice Fed Standard AIN93 Diet but Not in High Fat Diets

adiponectin and improve insulin action in energy-deficient ruminants facing metabolically demanding states such as early lactation.The study tested the hypothesis that FGF21 is unable to improve insulin action in energy-deficient ruminants as a consequence of its failure to increase plasma adiponectin.Methods: Non-pregnant, non-lactating ewes were treated for 12 days with FGF21 (provided by Eli Lilly) or excipient solution when well-fed (2-fold of maintenance energy requirement) or underfed (0.5-fold of maintenance energy requirement).Indices of insulin action measured include plasma glucose, insulin and adiponectin and glucose disposal during glucose and insulin tolerance tests.Expression of genes mediating FGF21 effects was measured in adipose tissue using quantitative RT-PCR.Results: Underfed ewes lost weight and had reduced plasma glucose and insulin, confirming negative energy balance.In underfed ewes, FGF21 retained the ability to reduce plasma glucose but not plasma insulin.FGF21 improved insulin action in both well-fed and underfed ewes during glucose and insulin tolerance tests and did so in the absence of increased plasma adiponectin in underfed ewes.Underfeeding reduced adipose tissue expression of the FGF21 co-receptor -Klotho and attenuated FGF21 stimulation of the FGF-responsive genes SPRY4 and DUSP4.FGF21 failed to increase adiponectin expression at both feeding levels.Conclusions: These data show that energy insufficiency alone does not prevent FGF21 improvement of insulin action in ruminants and that increased adiponectin production is not necessary for its insulin-sensitizing effects.