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. Author manuscript; available in PMC: 2012 Dec 1.
Published in final edited form as: Clin Exp Pharmacol Physiol. 2011 Dec;38(12):897–904. doi: 10.1111/j.1440-1681.2011.05606.x

Figure 1. Relationships and mechanisms underlying obesity and hypoadiponectinemia, and the consequences of hypoadiponectinemia.

Figure 1

Many transcription factors positively and negatively regulate adiponectin (APN) gene expression. Positive transcription factors, such as PPARγ, SREBP-1c, C/EBPα, and Foxol1/SIRT1, increase APN gene transcription. Negative transcription factors, such as IGFBP-3, CREB, ATF3, and NFAT, suppress APN gene transcription. Several molecular chaperones regulate the post-translation of APN, including Ero1-Lα, DsbA-L and ERp44. ERp44 retains APN intracellularly, while Ero1-Lα and DsbA-L facilitate APN multimerisation and secretion. In obesity, increased fat mass results in adipose tissue hypoxia, increasing endoplasmic reticular stress. Obesity is a low-grade chronic inflammatory state. ER stress and increased pro-inflammatory cytokines, such as TNF-α, IL-6, and IL-18 can inhibit the effect of positive transcription and post-translation factors, inducing production of inhibitory transcription factors, resulting in hypoadiponectinemia. Insulin resistance, type 2 diabetes, atherosclerosis formation, and increased myocardial ischaemia/reperfusion injury are all consequences of hypoadiponectinemia, and may all share a common etiological mechanism.