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Article

CTRP4 ameliorates dexamethasone‑induced insulin resistance through the IRS‑1/PI3K/AKT pathway in 3T3‑L1 adipocytes

  • Authors:
    • Maireyanmu Rouzi
    • Xi Sun
    • Luguang Sheng
    • Bilin Xu
    • Tao Lei
    • Jun Lu
    • Jie Gao
  • View Affiliations / Copyright

    Affiliations: Department of Endocrinology, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200062, P.R. China
  • Article Number: 101
    |
    Published online on: January 27, 2026
       https://doi.org/10.3892/mmr.2026.13811
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Abstract

In 2022, the World Health Organization estimated that globally, ~2.5 billion adults were overweight, including 890 million individuals with obesity. Adipose tissue dysfunction in obese individuals is a key contributor to the pathogenesis of insulin resistance. Within the present study, the association between serum levels of C1q/TNF‑related protein 4 (CTRP4) and insulin resistance (IR) in overweight/obese patients was investigated and the effects and mechanisms of CTRP4 on IR in dexamethasone‑induced 3T3‑L1 adipocytes were evaluated. A total of 98 overweight/obese patients were enrolled in the present study. Serum CTRP4 concentration levels were measured with ELISA kits. Correlations between CTRP4 and the homeostatic model assessment of IR (HOMA‑IR) were evaluated using Spearman's correlation analysis. Recombinant CTRP4 protein was administered to fully differentiated 3T3‑L1 adipocytes to explore the impact of CTRP4 on lipid accumulation. In addition, the effects of CTRP4 on restoring impaired glucose uptake were examined through the glucose oxidase‑peroxidase method. Molecular marker expression levels in the insulin signaling pathway, in 3T3‑L1 adipocytes with IR induced by 1 µM dexamethasone, were also examined, through western blotting. The expression levels of CTRP4 exhibited a negative association with body mass index (r=‑0.35; P<0.001), HOMA‑IR (r=‑0.24; P=0.048), waist circumference (r=‑0.38; P<0.001) and abdomen circumference (r=‑0.39; P<0.001). Following treatment of cells with recombinant CTRP4, a significant reduction in lipid accumulation was observed in 3T3‑L1 adipocytes, alongside with an increase in the glucose uptake rate in dexamethasone‑induced 3T3‑L1 adipocytes (all, P<0.05). Furthermore, a marked elevation in the expression levels of insulin receptor substrate 1 (IRS‑1), PI3K and AKT phosphorylation and GLUT4 was observed in the IR model of 3T3‑L1 adipocytes. Serum CTRP4 concentration levels were negatively correlated with IR in overweight/obese patients. CTRP4 suppressed lipid accumulation and promoted glucose uptake through the IRS‑1/PI3K/AKT signaling pathway and caused increased GLUT4 expression in 3T3‑L1 adipocytes.8

View Figures

Figure 1

Effects of CTRP4 on cell viability
and lipid accumulation of adipocytes. (A) Effect of CTRP4 (10, 100,
500, 1,000 and 2,000 ng/ml) on preadipocyte cell viability after
treatment for 24, 48 and 72 h. (B) Effect of CTRP4 (10, 100, 500,
1,000 and 2,000 ng/ml) on adipocyte cell viability after treatment
for 24, 48 and 72 h. (C) Representative Oil red O staining image of
CTRP4-treated (20, 200 and 1,000 ng/ml) 3T3-L1 adipocytes as well
as control, (magnification, ×200). *P<0.05, **P<0.01 and
***P<0.001 vs. con group. CTRP4, C1q/TNF-related protein 4; con,
control; con-, undifferentiated control group; con+, fully
differentiated control group.

Figure 2

Effects of CTRP4 on glucose uptake
and insulin resistance-related pathways in adipocytes. (A) Glucose
concentration in cell culture supernatants over time after
dexamethasone treatment (**P<0.01 and ***P<0.001 IR group vs.
CON group). (B) Glucose consumption was measured in 3T3-L1
adipocytes with insulin resistance upon stimulation with CTRP4 of
increasing concentrations (10, 100 and 1,000 ng/ml;
###P<0.001 IR group vs. CON group; **P<0.01 and
***P<0.001 CTRP4 group vs. IR group). 3T3-L1 adipocytes with
insulin resistance were treated with CTRP4 of increasing
concentration (10, 100 and 1,000 ng/ml) for 48 h. (C)
Representative western blotting images. (D-G) Semi-quantification
of western blotting results for (D) p-IRS-1, (E) p-PI3K, (F) p-AKT
and (G) GLUT4. (10, 100 and 1,000 ng/ml; #P<0.05,
##P<0.01, ###P<0.001 and
####P<0.0001 IR group vs. CON group; *P<0.05,
**P<0.01 and ***P<0.001 CTRP4 group vs. IR group). CTRP4,
C1q/TNF-related protein 4; CON, control; IR, insulin resistance;
p-, phosphorylated.
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Copy and paste a formatted citation
Spandidos Publications style
Rouzi M, Sun X, Sheng L, Xu B, Lei T, Lu J and Gao J: <p>CTRP4 ameliorates dexamethasone‑induced insulin resistance through the IRS‑1/PI3K/AKT pathway in 3T3‑L1 adipocytes</p>. Mol Med Rep 33: 101, 2026.
APA
Rouzi, M., Sun, X., Sheng, L., Xu, B., Lei, T., Lu, J., & Gao, J. (2026). <p>CTRP4 ameliorates dexamethasone‑induced insulin resistance through the IRS‑1/PI3K/AKT pathway in 3T3‑L1 adipocytes</p>. Molecular Medicine Reports, 33, 101. https://doi.org/10.3892/mmr.2026.13811
MLA
Rouzi, M., Sun, X., Sheng, L., Xu, B., Lei, T., Lu, J., Gao, J."<p>CTRP4 ameliorates dexamethasone‑induced insulin resistance through the IRS‑1/PI3K/AKT pathway in 3T3‑L1 adipocytes</p>". Molecular Medicine Reports 33.3 (2026): 101.
Chicago
Rouzi, M., Sun, X., Sheng, L., Xu, B., Lei, T., Lu, J., Gao, J."<p>CTRP4 ameliorates dexamethasone‑induced insulin resistance through the IRS‑1/PI3K/AKT pathway in 3T3‑L1 adipocytes</p>". Molecular Medicine Reports 33, no. 3 (2026): 101. https://doi.org/10.3892/mmr.2026.13811
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Spandidos Publications style
Rouzi M, Sun X, Sheng L, Xu B, Lei T, Lu J and Gao J: <p>CTRP4 ameliorates dexamethasone‑induced insulin resistance through the IRS‑1/PI3K/AKT pathway in 3T3‑L1 adipocytes</p>. Mol Med Rep 33: 101, 2026.
APA
Rouzi, M., Sun, X., Sheng, L., Xu, B., Lei, T., Lu, J., & Gao, J. (2026). <p>CTRP4 ameliorates dexamethasone‑induced insulin resistance through the IRS‑1/PI3K/AKT pathway in 3T3‑L1 adipocytes</p>. Molecular Medicine Reports, 33, 101. https://doi.org/10.3892/mmr.2026.13811
MLA
Rouzi, M., Sun, X., Sheng, L., Xu, B., Lei, T., Lu, J., Gao, J."<p>CTRP4 ameliorates dexamethasone‑induced insulin resistance through the IRS‑1/PI3K/AKT pathway in 3T3‑L1 adipocytes</p>". Molecular Medicine Reports 33.3 (2026): 101.
Chicago
Rouzi, M., Sun, X., Sheng, L., Xu, B., Lei, T., Lu, J., Gao, J."<p>CTRP4 ameliorates dexamethasone‑induced insulin resistance through the IRS‑1/PI3K/AKT pathway in 3T3‑L1 adipocytes</p>". Molecular Medicine Reports 33, no. 3 (2026): 101. https://doi.org/10.3892/mmr.2026.13811
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