Open Access

Shp2 suppresses fat accumulation in white adipose tissue by activating Wnt/β‑catenin signaling following vertical sleeve gastrectomy in obese rats with type‑2 diabetes

  • Authors:
    • Xiaoyang Qi
    • Ziying Sun
    • Xugang Li
    • Yuwen Jiao
    • Shuai Chen
    • Peng Song
    • Zhifen Qian
    • Jun Qian
    • Xusheng Qiu
    • Liming Tang
  • View Affiliations

  • Published online on: February 22, 2022     https://doi.org/10.3892/etm.2022.11231
  • Article Number: 302
  • Copyright: © Qi et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Adipogenesis and fat accumulation are closely associated with the development of obesity. Sleeve gastrectomy (SG) is an effective treatment for obesity and associated metabolic disorders. Leptin is downregulated after SG and Src homology phosphatase 2 (Shp2) has an important role in leptin signaling. The role of Shp2 in SG and the mechanisms of fat reduction following SG were further investigated in the current study. Sham and SG operations were performed on obese type‑2 diabetes model Sprague‑Dawley rats. Primary pre‑adipocytes were isolated from the inguinal white adipose tissue (ingWAT) of the rats. Shp2 expression in ingWAT pre‑adipocytes was silenced using small interfering RNA transfection. Shp2 function was inhibited using the specific inhibitor, SHP099. In addition, Shp2 was overexpressed using lentivirus. Gene and protein expression analysis was performed after adipocyte differentiation. Furthermore, Shp2‑overexpressing ingWAT pre‑adipocytes treated with the β‑catenin inhibitor, PNU‑74654, were also used for gene and protein expression analysis. Adipogenic markers, including triglycerides, peroxisome proliferator‑activated receptor γ (PPARγ), CCAAT/enhancer‑binding protein α (Cebpα), adiponectin, fatty acid‑binding protein 4 and leptin, were examined. Compared with the sham, triglyceride, leptin, PPARγ and Cebpα levels were significantly reduced in the ingWAT from the SG group. Shp2 expression levels were reduced following leptin treatment. Moreover, genetic analysis demonstrated depot‑specific adipogenesis following Shp2 silencing or inhibition in ingWAT pre‑adipocytes. Conversely, Shp2 overexpression decreased the expression of adipogenic markers by enhancing β‑catenin expression. PNU‑74654 treatment abolished the downregulation of adipogenic markers caused by Shp2 overexpression. SG decreased leptin levels in ingWAT, which in turn upregulated Shp2, and Shp2 suppressed fat accumulation and adipogenic differentiation by activating the Wnt/β‑catenin signaling pathway. Overall, this may represent a potential mechanism of fat reduction in SG, and Shp2 may serve as a potential therapeutic target for the treatment of obesity and type-2 diabetes.
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April-2022
Volume 23 Issue 4

Print ISSN: 1792-0981
Online ISSN:1792-1015

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Spandidos Publications style
Qi X, Sun Z, Li X, Jiao Y, Chen S, Song P, Qian Z, Qian J, Qiu X, Tang L, Tang L, et al: Shp2 suppresses fat accumulation in white adipose tissue by activating Wnt/β‑catenin signaling following vertical sleeve gastrectomy in obese rats with type‑2 diabetes. Exp Ther Med 23: 302, 2022
APA
Qi, X., Sun, Z., Li, X., Jiao, Y., Chen, S., Song, P. ... Tang, L. (2022). Shp2 suppresses fat accumulation in white adipose tissue by activating Wnt/β‑catenin signaling following vertical sleeve gastrectomy in obese rats with type‑2 diabetes. Experimental and Therapeutic Medicine, 23, 302. https://doi.org/10.3892/etm.2022.11231
MLA
Qi, X., Sun, Z., Li, X., Jiao, Y., Chen, S., Song, P., Qian, Z., Qian, J., Qiu, X., Tang, L."Shp2 suppresses fat accumulation in white adipose tissue by activating Wnt/β‑catenin signaling following vertical sleeve gastrectomy in obese rats with type‑2 diabetes". Experimental and Therapeutic Medicine 23.4 (2022): 302.
Chicago
Qi, X., Sun, Z., Li, X., Jiao, Y., Chen, S., Song, P., Qian, Z., Qian, J., Qiu, X., Tang, L."Shp2 suppresses fat accumulation in white adipose tissue by activating Wnt/β‑catenin signaling following vertical sleeve gastrectomy in obese rats with type‑2 diabetes". Experimental and Therapeutic Medicine 23, no. 4 (2022): 302. https://doi.org/10.3892/etm.2022.11231