Liver as a metabolic sensor in gestational diabetes: Implications for offspring’s liver and diabetes risk

Figure 1 Maternal hepatic adaptations in healthy pregnancy vs disruptions in gestational diabetes mellitus. ↑: Increased; ↓: Decreased; FXR: Farnesoid X receptor (a nuclear receptor regulating bile acid and lipid metabolism); VLDL: Very low-density lipoprotein; FGF21: Fibroblast growth factor 21; ANGPTL8: Angiopoietin-like protein 5; Hepatokines: Liver-secreted hormones that influence systemic metabolic homeostasis; Redox: Reduction-oxidation (balance between pro-oxidant and antioxidant processes in cells).

Figure 2 Mechanistic pathways linking maternal hepatic dysfunction in gestational diabetes mellitus to fetal programming and long-term offspring outcomes. GDM: Gestational diabetes mellitus; IR: Insulin resistance; UPR: Unfolded protein response; ER: Endoplasmic reticulum; TNF-α: Tumor necrosis factor-alpha; IL-6: Interleukin-6; CRP: C-reactive protein; ANGPTL8: Angiopoietin-like protein 8; FGF21: Fibroblast growth factor 21; FGF19: Fibroblast growth factor 19; FXR: Farnesoid X receptor;TGR5: Takeda G-protein receptor 5; SCFAs: Short-chain fatty acids; HPA: Hypothalamus-pituitary-adrenal; VLDLs: Very-low-density lipoproteins; FFAs: Free fatty acids; mTOR: Mechanistic target of rapamycin; SREBP-1c: Sterol regulatory element-binding protein 1c; FASN: Fatty acid synthase; IRS-1: Insulin receptor substrate-1; AKT: Protein kinase B; PPARGC1A: Peroxisome proliferator-activated receptor gamma coactivator 1-alpha; NAFLD: Non-alcoholic fatty liver disease; T2DM: Type 2 diabetes mellitus.