Role of peroxisome proliferator-activated receptor gamma (PPARγ) in the regulation of fatty acid metabolism related gene expressions in testis of men with impaired spermatogenesis

Alterations in glucose and fatty acid metabolism are believed to contribute to the development of heart failure. Peroxisome Proliferator Activated Receptor α (PPARα) is a transcription factor that regulates fatty acid metabolism and is frequently reported to be reduced in heart failure. However, it is controversial whether this decline in PPARα mediates the development of cardiac hypertrophy and heart failure. To improve our understanding of the role of cardiac PPARα we generated a tamoxifen inducible cardiac-specific PPARα knockout mouse (cPPAR -/- ). Control (Mer-Cre-Mer and Flox -/- ) mice and cPPAR -/- (Mer-Cre-Mer and Flox +/+ ) mice were treated with tamoxifen at ~2.5 months and were studied 5 weeks after treatment. We verified loss of cardiac PPARα using western blot. cPPAR -/- mice appear healthy with normal body weight gain and survival. To examine the impact of cardiac deletion of PPARα on cardiac function we performed echocardiography on control and cPPAR -/- . There was no reduction in systolic function between control and cPPAR -/- mice. Ejection fraction (Control, 56.3±0.9; cPPAR -/- , 59.7±0.1) and fractional shortening (Control, 29.1±0.5; cPPAR -/- , 31.5±0.1) were similar in cPPAR -/- compared to control hearts. Interestingly however, baseline heart rate was significantly lower in cPPAR -/- versus control mice (Control, 531.3±18.3; cPPAR -/- , 459.8±2.9 bpm). In addition to having normal cardiac function, heart weights were similar between control and cPPAR -/- mice. Overall, these data indicate that an acute reduction in myocardial PPARα per se does not cause cardiac dysfunction. However these data do not exclude the possibility that loss of PPARα could drive cardiac pathology in the context of other signals.

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SEMA3F-deficient colorectal cancer cells Promote lymphangiogenesis: fatty acid metabolism replace glycolysis for energy supply during lymphatic endothelial cells proliferation in tumor hypoxia microenvironment

10.1101/869644 ◽

2019 ◽

Author(s):

Xiaoyuan Fu ◽

Miaomiao Tao ◽

Hongbo Ma ◽

Cancan Wang ◽

Yanyan Li ◽

...

Keyword(s):

Colorectal Cancer ◽

Fatty Acids ◽

Endothelial Cells ◽

Fatty Acid ◽

Fatty Acid Metabolism ◽

Acid Metabolism ◽

Aerobic Glycolysis ◽

Peroxisome Proliferator ◽

Lymphatic Endothelial Cells ◽

Peroxisome Proliferator Activated Receptor

Abstractlymphangiogenesis as a process is colorectal cancer first metastasis via lymphatic vessels to proximal lymph nodes. The fuel metabolism in mitochondrial and support proliferation of lymphatic endothelial cells (LECs) remain elusive during lymphangiogenesis in tumor hypoxic microenvironment. Recent studies report that loss of SEMA3F critically contributes to lymphangiogenesis of the CRCs. Here, we silenced SEMA3F expression of CRCs and co-culture with hLECs, the tubulogenesis capacity and hLECs migration were escalated in the hypoxia, the hLECs mainly relied on fatty acid metabolism not aerobic glycolysis during lymphangiogenesis. SEMA3F-deficient CRCs up-regulated PMAKP expression and phosphorylation of hLECs, and activated its peroxisome proliferator-activated receptor (PPARs) and Peroxisome proliferator–activated receptor gamma coactivator-1 alpha (PGC-1a) facilitated their switched toward fatty acids (FA) catabolism. Furthermore, we observed that activation of the PGCI-PPAR lipid oxidation signaling pathway in hLECs was caused by the secretion of interleukin-6 by tumor cells.Taken together, this study indicates that CRCs with SEMA3F expression depletion significantly promotes lymphangiogenesis in hypoxia and faciliates the secretion of IL-6 in tumor cell, and activates mitochondria fatty acids oxidation (FAO) reaction in the hLECs by PGCI-PPAR signaling pathways to support its growth.

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