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