We found that both acute and chronic OA treatments reduced serum levels of triglycerides, total cholesterol, and LDL cholesterol, and decreased hepatic expression levels of peroxisome proliferator-activated receptor-γ coactivator-1β (PGC-1β), which is an important regulator in maintaining hepatic lipid homeostasis, and its downstream target genes.
The results showed that THC treatment significantly decreased lipid accumulation in OA-treated HepG2 cells, possibly, by inhibiting the expression of the lipogenic proteins, sterol regulatory element-binding protein 1 (SREBP-1c), peroxisome proliferator-activated receptor gamma (PPARγ), fatty acid synthase (FAS), and fatty acid-binding protein 4 (FABP4).
The Pro12Ala polymorphism of peroxisome proliferator-activated receptor-gamma (PPARgamma) has been associated with decreased obesity, insulin resistance, type 2 diabetes and other age-associated diseases such as cognitive impairment, hypertension, cancer, osteoarthritis.
PPARalpha and PPARgamma messenger RNA (mRNA) expression and protein synthesis in OA HSFs were measured by reverse transcription-polymerase chain reaction and electrophoretic mobility shift assay, respectively.
Our findings indicate AGEs induce an inflammatory response in human articular chondrocytes via the PPARγ/AMPK/SIRT-1 pathway, which is therefore a potential target in OA therapy.
Genotype and allele frequencies for either polymorphism in the PPARgamma gene did not differ significantly between patients with osteoarthritis and controls.
Further, 5Aza-confered protections against the cartilage damage and the associated abnormalities of OA-susceptible factors were significantly abrogated in PPARγ knockout mice.