Peroxisome Proliferator-Activated Gamma (PPAR-γ)

Authors

Affiliations

Nate Yomogida, B.S., SPT

Doctor of Physical Therapy

B.S. in Kinesiology

Chloë Kerstein, B.S., SPT

Doctor of Physical Therapy

B.A. in Neuroscience

type II nuclear receptor, initially recognized in adipose tissue for its role in fatty acid storage and glucose metabolism

It promotes lipid uptake and adipogenesis by increasing insulin sensitivity and adiponectin release.

Function

PPAR-γ has 3 primary functions

1. Regulate anabolism of the adipose tissue¹
2. Important role in glucose metabolism¹
3. Important role in cardiac development¹

Relationship to TGF-β

another superfamily, the transforming growth factor beta (TGF-β), and its receptors, all of which play a major role in Pulmonary artierial hypertension and kidney failure

TGF-β is a multifunctional cytokine that drives inflammation, fibrosis, and cell differentiation while PPARγ activation reverses these adverse events in many models

Genes

In humans, the PPAR-γ gene contains nine exons spanning over 100 kilobases located on chromosome 3¹

Gene regulation

PPAR-γ can regulate target genes by forming a heterodimer with the retinoid X receptor (RXR)¹

Mutations

Mutations in PPAR-γ gene have been associated with:

1. Lipid homeostasis dysfunction¹
2. Glucose homeostasis dysfunction¹

Which lead to secondary pathologies of:

1. Obesity¹
2. Type 2 Diabetes Mellitus (T2DM)¹
3. Thyroid Cancer¹

Facilitators

• Heat-shock protein 90 (Hsp90)

Inhibitors

• TGF-β1¹

References

1.

Kökény G, Calvier L, Hansmann G. PPAR\(\gamma\) and TGF\(\beta\)-Major Regulators of Metabolism, Inflammation, and Fibrosis in the Lungs and Kidneys. International Journal of Molecular Sciences. 2021;22(19):10431. doi:10.3390/ijms221910431