Related Experiment Video

Updated: Sep 29, 2025

Differentiated Mouse Adipocytes in Primary Culture: A Model of Insulin Resistance
09:48

Differentiated Mouse Adipocytes in Primary Culture: A Model of Insulin Resistance

Published on: February 17, 2023

3.0K

Thyroid-Stimulating Hormone Inhibits Insulin Receptor Substrate-1 Expression and Tyrosyl Phosphorylation in 3T3-L1

Yajing Zhang1, Ling Feng2

  • 1NHC Key Laboratory of Hormones and Development, Tianjin Key Laboratory of Metabolic Diseases, Chu Hsien-I Memorial Hospital & Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin 300134, China.

Disease Markers
|March 24, 2022
PubMed
Abstract

Insights

Thyroid-stimulating hormone (TSH) may cause insulin resistance by reducing insulin receptor substrate-1 (IRS-1) expression and phosphorylation. This occurs through TSH-induced TNF-α secretion, which activates NF-κB signaling in adipocytes.

Area of Science:

  • Endocrinology
  • Molecular Biology
  • Cell Biology

Background:

  • Thyroid-stimulating hormone (TSH) is linked to insulin resistance in adipocytes.
  • The precise mechanism underlying this association remains unclear.
  • This study investigates TSH's role in suppressing insulin receptor substrate-1 (IRS-1) and its tyrosyl phosphorylation.

Purpose of the Study:

  • To elucidate the mechanism by which TSH may contribute to insulin resistance.
  • To examine the effect of TSH on IRS-1 expression and phosphorylation in adipocytes.
  • To determine the role of TNF-α and NF-κB signaling in TSH-mediated effects.

Main Methods:

  • 3T3-L1 preadipocytes were differentiated into adipocytes.
  • TSH treatment was administered at varying concentrations (0.01–1.0 mIU/ml).
  • Measurements included TNF-α secretion (ELISA), NF-κB DNA-binding activity (EMSA), and IRS-1 levels/phosphorylation (Western blotting, immunoprecipitation).

Main Results:

  • TSH dose-dependently increased TNF-α secretion, correlating with NF-κB activation.
  • TSH inhibited insulin-stimulated IRS-1 tyrosyl phosphorylation.
  • Inhibitors of NF-κB (BAY 11-7082) and PKA (H89), and a TNF-α antagonist (WP9QY) blocked TSH's effects.

Conclusions:

  • TSH suppresses IRS-1 expression and tyrosyl phosphorylation in adipocytes.
  • This suppression is mediated by TSH-induced TNF-α production via NF-κB activation.
  • TSH may play a significant role in the development of insulin resistance.

More Related Videos

An Adipocyte Cell Culture Model to Study the Impact of Protein and Micro-RNA Modulation on Adipocyte Function09:20

An Adipocyte Cell Culture Model to Study the Impact of Protein and Micro-RNA Modulation on Adipocyte Function

Published on: May 4, 2021

3.8K
Measuring the Rate of Lipolysis in Ex Vivo Murine Adipose Tissue and Primary Preadipocytes Differentiated In Vitro09:41

Measuring the Rate of Lipolysis in Ex Vivo Murine Adipose Tissue and Primary Preadipocytes Differentiated In Vitro

Published on: March 17, 2023

3.1K

Related Concept Videos

Insulin: The Receptor and Signaling Pathways01:28

Insulin: The Receptor and Signaling Pathways

Insulin action is mediated through a receptor tyrosine kinase, akin to the IGF-1 receptor. The number of receptors per cell varies significantly, from 40 on erythrocytes to 300,000 on adipocytes and hepatocytes. The insulin receptor consists of linked α/β subunit dimers, forming a heterotetramer glycoprotein with two extracellular α subunits and two β subunits spanning the membrane. The α subunits inhibit the inherent tyrosine kinase activity of the β subunits, but...
1.6K
Synthesis and Regulation of Thyroid Hormones01:20

Synthesis and Regulation of Thyroid Hormones

Low blood levels of the thyroid hormones — triiodothyronine (T3) and thyroxine (T4) — signal the hypothalamus to release the thyrotropin-releasing hormone (TRH). TRH then reaches the pituitary gland and stimulates the release of thyroid-stimulating hormone(TSH) into the bloodstream.
Upon reaching the thyroid gland, TSH stimulates the follicular cells' active uptake of iodide ions from the blood. The ions diffuse to the apical surface of the cells and are oxidized to iodine. The...
5.3K
Functions of Thyroid Hormones01:18

Functions of Thyroid Hormones

The thyroid hormone (TH) plays a pivotal role in the intricate orchestration of physiological processes, exerting profound effects on development, metabolism, and homeostasis throughout different life stages.
TH is indispensable for the normal development and maturation of the skeletal, muscular, and nervous systems during fetal and childhood growth. It facilitates bone mineral turnover and regulates protein synthesis in developing tissues, contributing significantly to overall growth and...
3.3K
TGF - β Signaling Pathway01:16

TGF - β Signaling Pathway

The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors...
7.9K
PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a...
4.1K
Cell Specific Gene Expression01:58

Cell Specific Gene Expression

Multicellular organisms contain a variety of structurally and functionally distinct cell types, but the DNA in all the cells originated from the same parent cells. The differences in the cells can be attributed to the differential gene expression. Liver cells, whose functions include detoxification of blood, production of bile to metabolize fats, and synthesis of proteins essential for metabolism, must express a specific set of genes to perform their functions. Gene expression also varies with...
14.1K