Fig. 7. Overexpression or knockin of PNPLA3-I148M in mice impairs hepatic TG secretion.
a TG secretion from primary hepatocytes isolated from WT mice, infected with control, PNPLA3 WT or PNPLA3 I148M expressing adenovirus, and treated with 250 μM 1:1 OA:LA and 25 μM glycerol containing 3H-glycerol (n = 3/group). b–h 10-week-old WT mice fed a chow diet were injected with either Ad-null or Ad-PNPLA3-I148M. Tissues were collected following a 12-h fast for lipid (n = 8/group) and lipidomic analysis (n = 3/group). b Total liver TG content. Individual FA species composition of TG presented as absolute FA abundance (c) and as percentage of the total FA pool (d). e Abundance of total PLs. f Abundance of major PL classes. Individual FA species composition of PE presented as absolute FA abundance (g) and as percentage of the total FA pool (h). Individual FA species composition of PC presented as absolute FA abundance (i) and as percentage of the total FA pool (j). k TG secretion from primary hepatocytes isolated from WT or PNPLA3-I148M-KI mice following treatment with 250 μM 1:1 OA:LA and 25 μM glycerol containing 3H-glycerol (n = 6/group). l–o 9-12-wk-old WT (n = 10) and I148M-KI (n = 7) mice were fed COWD and given access to fructose/glucose in drinking water for 3 weeks. l Total liver TG content. m Total plasma TG content. n Representative time course of hepatic TG secretion in WT (n = 10) and PNPLA3-I148M-KI (n = 7) mice upon administration of Poloxomer-407 (o) Data from (n) represented as secretion rate per hour. All error bars represent mean ± SD. *p < 0.05, **p < 0.01, ***p < 0.001 ****p < 0.0001, two-sided t test. Specific p values: a p = 0.0445. b p = 2.16E-04. c 14:0, p = 8.65E-04; 16:0, p = 5.10E-04; 16:1, p = .00215; 18:0, p = 1.75E-04; 18:1, p = 2.91E-04; 18:2, p = 2.36E-05; 18:3, p = 1.89E-04; 20:4, p = 0.434. d 14:0, p = 0.00386; 16:0, p = 0.6.23E-04; 18:1, p = 0.573; 18:2, p = 0.611; 18:3, p = 0.0700; 20:4, p = 0.00793. e p = 0.0406. f PE, p = 0.0487; PC, p = 0.0258. g 16:0, p = 0.0801; 18:2, p = 0.00376; 20:4, p = 0.00670. h 18:2, p = 0.0277; 20:3, p = 0.0618; 20:4, p = 0.114; 22:5, p = 0.0110. i 16:0, p = 0.00707; 18:1, p = 0.126; 18:2, p = 0.00415; 20:4, p = 0.021. j 18:0, p = 0.00761; 18:2, p = 3.43E-06; 20:4, p = 0.0429; 22:5, p = 0.00981. k p = 2.96E-04. l p = 1.60E-04. m p = 0.0223. n 1 h, p = 0.731; 2 h, p = 0.0269; 3 h, p = 4.19E-04. o p = 0.000522.