Elsevier

Vitamins & Hormones

Volume 90, 2012, Pages 143-162
Vitamins & Hormones

Chapter Six - Adiponectin and PPARγ: Cooperative and Interdependent Actions of Two Key Regulators of Metabolism

https://doi.org/10.1016/B978-0-12-398313-8.00006-3Get rights and content

Abstract

The recent advances in the understanding of adiponectin and other adipokines have highlighted the role of adipose tissue as an active endocrine organ. One of the central regulators of adipocyte biology is peroxisome proliferator-activated receptor gamma (PPARγ), a transcription factor that induces the adipogenic gene expression program during development, promotes adipose remodeling, and regulates the functions of adipocytes in lipid storage, adipokine secretion, and energy homeostasis. Activation of PPARγ results in increased insulin sensitivity in skeletal muscle and liver and improves the secretory profile of adipose tissue, favoring release of insulin-sensitizing adipokines, such as adiponectin, and reducing inflammatory cytokines. Increased adiponectin production is likely a significant mediator of the systemic effects of PPARγ activation. This chapter will review the interplay between PPARγ and adiponectin in regulating metabolism, presenting evidence that PPARγ regulates adiponectin gene expression, processing, and secretion and that the two proteins have overlapping effects on downstream metabolic pathways.

Section snippets

PPARγ Activity Correlates with Adiponectin Hormone Levels

The idea that there is a physiologically important link between peroxisome proliferator-activated receptor gamma (PPARγ) and adiponectin is based mainly on the observations that under many circumstances changes in PPARγ activity correlate with altered adiponectin hormone levels. This correlative linkage has been observed in patients, animal models, and cell culture and is apparent whether PPARγ activity has been altered by pharmacological or genetic means. In addition, on a more mechanistic

PPARγ Regulates Adiponectin Gene Transcription

If PPARγ regulates the level of adiponectin, as the genetic and pharmacological data described above suggest, then either the adiponectin gene itself or genes encoding proteins involved in the processing and secretion of the hormone are likely to be direct transcriptional targets of PPARγ. The following section is a review of the evidence that this is indeed the case. This will be preceded by a brief overview of the basic molecular biology of PPARγ.

PPARγ is a member of the nuclear receptor

PPARγ Regulates Adiponectin Hormone Secretion

Following transcription and translation, the nascent adiponectin peptide undergoes a series of posttranslational modifications before it becomes biologically active, including hydroxylation, glycosylation, oligomerization, secretion, and proteolysis (Wang, Lam, Yau, & Xu, 2008). The primary role of PPARγ in the regulation of this complex process is a point of some debate. While there is evidence of direct transcriptional activation of the adiponectin gene by PPARγ, some groups suggest that this

PPARγ and Adiponectin Regulate Similar Physiological Pathways

In addition to the direct effects of PPARγ on adiponectin hormone production described above, there are other less direct, but not necessarily less important, sites of interaction between these two important metabolic regulators. In the most general sense, both proteins are responsible for inducing similar physiological effects, which can generally be described as improving various aspects of insulin sensitivity in multiple tissues. In part, this is due to the obvious fact that one of the

Conclusion

Given the strong similarity in the general physiological roles of the PPARγ and adiponectin, it might not be surprising that there are numerous functional links between the two proteins. On the one hand, it may be accurate to think of adiponectin and its signaling pathway as simply downstream targets of PPARγ and that PPARγ is the “master regulator” of this process. On the other hand, it may be more correct to consider the two proteins as different components of the same complex physiological

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