Betulinic acid improves TNF-α-induced insulin resistance by inhibiting negative regulator of insulin signalling and inflammation-activated protein kinase in 3T3-L1 adipocytes

Abstract

Context

Obesity is related to insulin resistance, and adipose tissue-secreted TNF-α may play a role in inducing obesity. TNF-α activates inflammatory protein kinase and impairs insulin signalling.

Objectives

We investigated the effect of betulinic acid on insulin resistance caused by TNF-α treatment in 3T3-L1 adipocytes.

Material and methods

3T3-L1 was exposed to TNF-α in the presence and absence of betulinic acid. Various parameters such as glucose uptake assay, cell viability, expression of proteins involved in insulin resistance were studied.

Results

Betulinic acid increased glucose uptake in TNF-α pre-treated cells and inhibited the activation of PTP1B and JNK and reduced IκBα degradation. Tyrosine phosphorylation was increased, and serine phosphorylation was decreased in IRS-1.

Discussion

Betulinic acid restored TNF-α impaired insulin signalling and increased PI3K activation and phosphorylation of Akt and increased plasma membrane expression of GLUT 4, which stimulated glucose uptake concentration-dependently.

Conclusion

These results suggest that betulinic acid is effective at improving TNF-α-induced insulin resistance in adipocytes via inhibiting the activation of negative regulator of insulin signalling and inflammation-activated protein kinase and may potentially improve insulin resistance.

Keywords:

• Betulinic acid
• insulin resistance
• PTP1B
• JNK
• IRS-1

Author contributions

HA Lee and JS Han designed the research; HA Lee and JK Lee performed the research; HA Lee and JS Han analysed the data; HA Lee wrote the paper; JS Han provided critical feedback and revised the manuscript. All authors read and approved the final manuscript.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

The data that support the findings of this study are available from the corresponding author, JS Han, upon reasonable request.

Additional information

Funding

This work was supported by a 2-year research grant of Pusan National University.