Peptide Fraction pOh2 Exerts Antiadipogenic Activity through Inhibition of C/EBP-αand PPAR-γExpression in 3T3-L1 Adipocytes

Abstract

Many studies have comprehensively examined the venom of Ophiophagus hannah snake. Its venom comprises different compounds exhibiting a wide range of pharmacological activities. In this investigation, four peptide fractions (PFs), ranging from 3 kDa to 10 kDa, isolated from the Vietnamese snake venom of O. hannah were separated by HPLC and investigated for their inhibitory activity on adipogenesis in 3T3-L1 adipocytes. The most effective PF was then further purified, generating two peptides, pOh1 and pOh2. Upon investigation of these two peptides on 3T3-L1 adipocytes, it was revealed that, at 10 μg/mL, pOh2 was able to inhibit the lipid accumulation in 3T3-L1 adipocytes by up to 56%, without affecting cell viability. Furthermore, the pOh2 downregulated the gene expression of important transcription factors C/EBP-α and PPAR-γ. In addition, aP2 and GPDH adipocyte-specific markers were also significantly reduced compared to untreated differentiated cells. Taken together, pOh2 inhibited the expression of key transcription factors C/EBP-α and PPAR-γ and their target genes, aP2 and GPDH, thereby blocking the adipocyte differentiation. In conclusion, this novel class of peptide might have potential for in vivo antiobesity effects.

<p>The Inhibitory Effects of Juglanin on Adipogenesis in 3T3-L1 Adipocytes</p>

“…Inhibiting the expression of these two important transcription factors has been shown to reduce adipocyte differentiation in 3T3-L1 preadipocytes. 33 While previous research found that walnut polyphenols increased PPARα expression, 34 we found that juglanin reduced the increase in the expression of both C/EBPα and C/EBPβ without affecting PPARα or PPARγ expression in 3T3-L1 cells, thereby indicating an alternate mechanism of action. The transcripts of PPARγ gene produce two protein isoforms, the shorter PPARγ1, and the longer PPARγ2.…”

Structurally Diverse Bisbenzylisoquinoline Alkaloids with Antiadipogenic Activity through PPARγ Downregulation from the Embryo of Nelumbo nucifera Seeds

“…PPARγ is a crucial transcription factor in cellular differentiation and plays a key role in adipocyte production as well as glucose and lipid metabolism. Suppressing 3T3-L1 preadipocyte expression of PPARγ suppresses adipocyte differentiation, resulting in antiadipogenic activity . Lentivirus ( PPARγ luciferase reporter)-transfected 3T3-L1-Lenti- PPARγ -Luc cells were used for the preliminary verification of the inhibitory effect on PPARγ expression.…”

“…Suppressing 3T3-L1 preadipocyte expression of PPARγ suppresses adipocyte differentiation, resulting in antiadipogenic activity. 28 Lentivirus ( PPARγ luciferase reporter)-transfected 3T3-L1-Lenti- PPARγ -Luc cells 29 were used for the preliminary verification of the inhibitory effect on PPARγ expression. Neferine ( 7 ), a known compound isolated in this study, has been reported to have a PPARγ inhibitory effect, so it was also used as a positive control for the PPARγ inhibition assay.…”