Dayarathne LA, et al. J Vet Sci. 2021 Jul;22(4):e55. https://doi.org/10.4142/jvs.2021.22.e55

Dayarathne LA, et al. J Vet Sci. 2021 Oct;22(6):e92. https://doi.org/10.4142/jvs.2021.22.e92

Rajan P, et al. J Vet Sci. 2021 Nov;23:e4. https://doi.org/10.4142/jvs.21256

The present study aims to explore the probable anti-adipogenesis effect of Dictyopteris divaricata (D. divaricata) in 3T3-L1 preadipocytes by regulating heme oxygenase-1 (HO-1). The extract of D. divaricata retarded lipid accretion and decreased triglyceride (TG) content in 3T3-L1 adipocytes but increased free glycerol levels. Treatment with the extract inhibited lipogenesis by inhibiting protein expressions of fatty acid synthase (FAS) and lipoprotein lipase (LPL), whereas lipolysis increased by activating phosphorylation of hormone-sensitive lipase (p-HSL) and AMP-activated protein kinase (p-AMPK). The extract inhibited adipocyte differentiation of 3T3-L1 preadipocytes through down-regulating adipogenic transcription factors, including peroxisome proliferator-activated receptor gamma (PPARγ) and CCAAT/enhancer-binding protein α (C/EBPα), and sterol regulatory element-binding protein 1 (SREBP1). This is attributed to the triggering of Wnt/β-catenin signaling. In addition, this study found that treatment with the extract activated HO-1 expression. Pharmacological approaches revealed that treatment with Zinc Protoporphyrin (ZnPP), an HO-1 inhibitor, resulted in an increase in lipid accumulation and a decrease in free glycerol levels. Finally, three adipogenic transcription factors, such as PPARγ, C/EBPα, and SREBP1, restored their expression in the presence of ZnPP. Analysis of chemical constituents revealed that the extract of D. divaricata is rich in 1,4-benzenediol, 7-tetradecenal, fucosterol, and n-hexadecanoic acid, which are known to have multiple pharmacological properties.

Nonalcoholic fatty liver disease (NAFLD) is a progressive metabolic disorder with limited therapeutic options. This study investigates the hepatoprotective potential of two novel Oligopeptides, LLRLTDL (Bu1) and GYALPCDCL (Bu2), against hepatic steatosis in oleic acid (OA) induced HepG2 cells and in diet-induced obese mice. In vitro, Bu1 and Bu2 suppressed fatty acid synthesis and ameliorated lipid accumulation by downregulating the expression of key lipogenic transcription factors, including PPAR-γ, SREBP-1c, C/EBP-α, and FAS. Peptide treatment also enhanced phosphorylation of AMPK and HSL, indicating suppression of lipogenesis and promoting fatty acid oxidation. In vivo, Bu1 and Bu2 administration attenuated body weight gain, relative liver weight, hepatic lipid accumulation, and improved hepatic lipid profiles, including TG, FFA, free glycerol release, HDL, and LDL, independent of food intake. Liver histology further confirmed reversal of hepatic steatosis following peptide administration. Of note, these ameliorative effects of Bu1 and Bu2 were further substantiated at the molecular level, as evidenced by Western blot analysis. Moreover, two peptides exerted anti-inflammatory effects by reducing pro-inflammatory cytokine levels and alleviating hepatocellular injury, indicated by lower serum AST and ALT levels. Collectively, these findings suggest the potential of Bu1 and Bu2 as bioactive peptide-based interventions for NAFLD, offering a strong rationale for their further investigation in the treatment of metabolic liver disease.