# Taraxasterol Acetate Attenuates TNF-α-Induced Insulin Resistance via Regulation of Insulin Signaling, Inflammation, and Lipid Metabolism in 3T3-L1 Cells

## TL;DR

Taraxasterol acetate reduces insulin resistance in fat cells by improving insulin signaling, reducing inflammation, and enhancing lipid metabolism.

## Contribution

Taraxasterol acetate is shown to mitigate TNF-α-induced insulin resistance through multiple metabolic pathways in 3T3-L1 adipocytes.

## Key findings

- TXA enhances glucose uptake via GLUT4 translocation and activates IRS-1/PI3K/Akt and AMPK signaling.
- TXA reduces inflammation and oxidative stress by inhibiting NF-κB, JNK, and lowering ROS levels.
- TXA improves lipid metabolism and mitochondrial function by upregulating fatty acid oxidation and PGC-1α/TFAM.

## Abstract

Insulin resistance,
obesity, and type 2 diabetes mellitus (T2DM)
are interrelated metabolic disorders with rising global prevalence.
Triterpenes, known for their diverse pharmacological properties, have
shown potential in improving insulin sensitivity and exerting antidiabetic
and antiobesity effects. This study evaluated the effects of taraxasterol
acetate (TXA), a pentacyclic triterpene isolated from Eupatorium ballotaefolium, on TNF-α-induced
insulin resistance and lipolysis in mature 3T3-L1 adipocytes. TXA
significantly enhanced glucose uptake in insulin-resistant adipocytes
by promoting GLUT4 translocation by activating the IRS-1/PI3K/Akt
signaling pathway and upregulating AMPK expression. TXA also inhibited
NF-κB and JNK signaling, reducing inflammation and mitigated
oxidative stress by decreasing intracellular reactive oxygen species
(ROS) levels and enhancing antioxidant enzyme activity, including
superoxide dismutase (SOD) and catalase (CAT). Moreover, TXA normalized
adipokine secretion by increasing leptin and adiponectin levels, and
promoted lipid accumulation through the modulation of PPARγ,
HSL, ATGL, and Perilipin expression. TXA further improved lipid metabolism
by upregulating fatty acid β-oxidation genes (ACOX1, CPT1b)
and supported mitochondrial function by enhancing PGC-1α and
TFAM expression. Collectively, these findings demonstrate that TXA
mitigates TNF-α-induced insulin resistance by improving insulin
signaling, suppressing inflammation and oxidative stress, and improving
lipid and mitochondrial metabolism. These results suggest that TXA
is a promising therapeutic candidate for the prevention and treatment
of insulin resistance and related metabolic disorders.