Ppara, also known as peroxisome proliferator-activated receptor alpha, is a ligand-activated transcription factor. It is a key mediator of lipid metabolism, regulating genes involved in fatty acid metabolism [4]. It is also associated with pathways like the hypoxia-inducible factor pathway [3]. Ppara has biological importance in multiple tissues, and genetic models such as mouse models are valuable for studying its functions.

In Alzheimer's disease (AD) murine models, activation of Ppara-mediated autophagy by agonists gemfibrozil and Wy14643 decreased amyloid pathology and reversed memory deficits, indicating Ppara's role in regulating autophagy for Aβ clearance [1]. In non-alcoholic fatty liver disease (NAFLD), MIR20B targets Ppara, and its overexpression increases hepatic lipid accumulation, while inhibition of Mir20b improves insulin sensitivity and reduces NAFLD progression [2]. In COPD patients, Ppara expression is downregulated, exacerbating disease progression [3]. In mouse liver, Ppara activation promotes Cbfa2t3 induction, and Cbfa2t3 -/- mice show increased insulin resistance and lipid accumulation [4]. In non-alcoholic steatohepatitis (NASH), intestinal Ppara promotes NASH progression through modulating fatty acid uptake via FABP1 [5].

In conclusion, Ppara is crucial for lipid metabolism and is involved in various disease conditions. Gene knockout mouse models have revealed its roles in AD, NAFLD, COPD, liver lipid metabolism, and NASH, enhancing our understanding of the biological processes and potentially leading to new therapeutic strategies for these diseases.

References:

1. Luo, Rongcan, Su, Ling-Yan, Li, Guiyu, Li, Jiali, Yao, Yong-Gang. 2019. Activation of PPARA-mediated autophagy reduces Alzheimer disease-like pathology and cognitive decline in a murine model. In Autophagy, 16, 52-69. doi:10.1080/15548627.2019.1596488. https://pubmed.ncbi.nlm.nih.gov/30898012/

2. Lee, Yo Han, Jang, Hyun-Jun, Kim, Sounkou, Nam, Dougu, Choi, Jang Hyun. 2021. Hepatic MIR20B promotes nonalcoholic fatty liver disease by suppressing PPARA. In eLife, 10, . doi:10.7554/eLife.70472. https://pubmed.ncbi.nlm.nih.gov/34964438/

3. Li, Honge, Pei, Wenhui, Wang, Yunchao, Yang, Zhen, Wang, Xinhua. . Mechanism of Action of the Plateau-Adapted Gene PPARA in COPD. In Frontiers in bioscience (Landmark edition), 29, 68. doi:10.31083/j.fbl2902068. https://pubmed.ncbi.nlm.nih.gov/38420801/

4. Kim, Donghwan, Ha, Sang Keun, Gonzalez, Frank J. 2024. CBFA2T3 Is PPARA Sensitive and Attenuates Fasting-Induced Lipid Accumulation in Mouse Liver. In Cells, 13, . doi:10.3390/cells13100831. https://pubmed.ncbi.nlm.nih.gov/38786053/

5. Yan, Tingting, Luo, Yuhong, Yan, Nana, Qu, Aijuan, Gonzalez, Frank J. 2022. Intestinal peroxisome proliferator-activated receptor α-fatty acid-binding protein 1 axis modulates nonalcoholic steatohepatitis. In Hepatology (Baltimore, Md.), 77, 239-255. doi:10.1002/hep.32538. https://pubmed.ncbi.nlm.nih.gov/35460276/