Homocysteine upregulates resistin production from adipocytes in vivo and in vitro

  1. Yin Li, MD, PhD,
  2. Changtao Jiang, MD,
  3. Guoheng Xu, MD, PhD,
  4. Nanping Wang, MD, PhD,
  5. Yi Zhu, MD, PhD,
  6. Chaoshu Tang, MD, PhD and
  7. Xian Wang, MD, PhD (xwang{at}bjmu.edu.cn)
  1. Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University; Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Beijing 100083, P. R. China

    Abstract

    Objective: Homocysteine (Hcy) is epidemiologically related to insulin resistance, which has been speculated as a low-grade systemic inflammatory condition. Resistin acts as a critical mediator of insulin resistance associated with inflammatory conditions. We aimed to determine whether Hcy can induce insulin resistance by directly regulating the expression and secretion of resistin from adipose tissue.

    Research Design and Methods: The effect of Hcy on the expression and secretion of resistin and insulin resistance was investigated using primary rat adipocytes and mice with hyperhomocysteinemia (HHcy).

    Results: Hcy impaired glucose transport and particularly the insulin signaling pathway as shown by decreased insulin-stimulated tyrosine phosphorylation of IR and IRS-1, increased serine phosphorylation of IRS-1, and inhibited Akt phosphorylation both in vitro and in vivo, and these impairments were accompanied by an increase in resistin expression. Compared with normal mice, HHcy mice with a clinically relevant level of plasma Hcy (19 μM) showed significantly increased resistin production from adipose tissue (33.38±3.08 vs 19.27±1.71 ng/ml, P<0.01). Hcy (300-1000 μM) also increased the mRNA expression of resistin in primary rat adipocytes in a time- and concentration-dependent manner, with maximal induction at 24 h of approximately 4-fold with 1000 μM. In addition, Hcy-induced resistin expression attenuated by treatment with reactive oxygen species (ROS) scavengers, protein kinase C (PKC) and nuclear factor (NF)-κB inhibitors implies a role in the process for ROS, PKC, and NF-κB.

    Conclusions: HHcy may promote insulin resistance through the induction of resistin expression and secretion from adipocytes via the activation of the ROS-PKC-NF-κB pathway.

    Footnotes

      • Received May 8, 2007.
      • Accepted January 8, 2008.

    This Article

    1. Diabetes
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