Establishment of a new nonalcoholic steatohepatitis model; Ovariectomy exacerbates nonalcoholic steatohepatitis-like pathology in diabetic rats

Loss of Carnitine Palmitoyltransferase 1a Reduces Docosahexaenoic Acid-Containing Phospholipids and Drives Sexually Dimorphic Liver Disease in Mice

“…A reduction in PEMT has been shown to deplete hepatic and plasma DHA-containing PC (65), promote steatosis, inflammation, and fibrosis in mouse models of SLD (66)(67)(68), and associate with an increased risk of worsened liver dysfunction in humans (69, 70). Notably, PEMT is responsive to estrogen due to three evolutionarily conserved estrogen regulatory motifs within the promoter (71), and loss of ovarian sex hormones by ovariectomy promotes SLD and reduces Pemt gene expression in the liver (72). These publications largely support our findings where we show female LKO lose their protection from diet-induced SLD, which associates with lower PEMT protein and PC:PE ratios compared to female control mice.…”

Potential therapeutic implications of histidine catabolism by the gut microbiota in NAFLD patients with morbid obesity

“…Therefore, to further validate our findings, we performed additional experiments in two additional murine models of NAFLD: (1) the genetic leptin-deficient ob/ob mouse 22 and (2) the surgical ovariectomy (OVX) rat. 23 In the ob/ob model, HAA supplementation induced apparent macroscopic ( Figure 4 A) and microscopic improvements ( Figure 4 B) with a similar number of lipid droplets ( Figure 4 C) but with a reduced lipid surface (p = 0.0045; Figure 4 D). These features were accompanied by a tendency of reduced total hepatic lipid content (although the results did not reach statistical significance, p = 0.09; Figure 4 E) and a reduction in the expression of genes involved in de novo lipogenesis ( Acc1 , p = 0.0081; Fasn , p = 0.030; Scd1 , p = 0.017; Figure 4 F).…”

Loss of carnitine palmitoyltransferase 1a reduces docosahexaenoic acid-containing phospholipids and drives sexually dimorphic liver disease in mice

“…A reduction in PEMT has been shown to deplete hepatic and plasma DHA-containing PC [ 64 ], promote steatosis, inflammation, and fibrosis in mouse models of SLD [ [65] , [66] , [67] ], and associate with an increased risk of worsened liver dysfunction in humans [ 68 , 69 ]. Notably, PEMT is responsive to estrogen due to three evolutionarily conserved estrogen regulatory motifs within the promoter [ 70 ], and loss of ovarian sex hormones by ovariectomy promotes SLD and reduces Pemt gene expression in the liver [ 71 ]. These publications largely support our findings where we show female LKO lose their protection from diet-induced SLD, which associates with lower PEMT protein and PC:PE ratios compared to female control mice.…”