Extended Data Fig. 3: Metformin inhibits complex I to drive Lac-Phe production in Caco-2 cells.
From: Lac-Phe mediates the effects of metformin on food intake and body weight
(a-b) Cellular respiration of Caco-2 cells following treatment with the indicated concentrations of metformin (a, n = 5/concentration) or biguanide (b, n = 6/concentration) overnight. (c-d) Percent inhibition of basal respiration (c, n = 5/concentration for metformin; n = 6/concentration for buformin and phenformin) and Lac-Phe concentration in media (d, n = 3/concentration) following overnight treatment of Caco-2 cells with the indicated biguanide at the indicated concentrations. (e) Fold-change in media Lac-Phe levels in Caco-2 cells following overnight treatment with the indicated oxidative phosphorylation inhibitor at the indicated concentration (n = 3/concentration) (f-g) Fold-change in media Lac-Phe levels or 13C-labeled Lac-Phe levels in Caco-2 cells (n = 3/condition) using either 13C-labeled glucose (f) or 13C-labeled lactate (g). (h) Cell viability after treated with Lac-Phe at indicated concentrations overnight as revealed by CCK-8 assay (n = 5/concentration). P values in (e) were calculated using two-sided one sample t test. *p < 0.05, **p < 0.01, *** p < 0.001. The exact p values in (e) are: 0.0050, 0.0144, 0.3965, 0.9973, 0.0232, 0.0004, 0.0064, 0.0007. N numbers in (a-h) represent biological independent samples. All error bars are SEM.
