LPL/AQP7/GPD2 promotes glycerol metabolism under hypoxia and prevents cardiac dysfunction during ischemia

• DOI: 10.1096/fj.202100882r
• Publication Date: 2021-11-22T15:48:17Z
• Authors: Sohta Ishihama; Satoya Yoshida; Tatsuya Yoshida; Yu Mori; Noriyuki Ouchi; Shunsuke Eguchi; Teruhiro Sakaguchi; Takuma Tsuda; Katsuhiro Kato; Yuuki Shimizu; Koji Ohashi; Takahiro Okumura; Yasuko K. Bando; Hiroaki Yagyu; Nina Wettschureck; Naoto Kubota; Stefan Offermanns; Takashi Kadowaki; Toyoaki Murohara; Mikito Takefuji
• Keywords: Adenosine triphosphate; Hypoxia; Dihydroxyacetone phosphate

In the heart, fatty acid is a major energy substrate to fuel contraction under aerobic conditions. Ischemia downregulates metabolism adapt limited oxygen supply, making glucose preferred substrate. However, mechanism underlying myocardial metabolic shift during ischemia remains unknown. Here, we show that lipoprotein lipase (LPL) expression in cardiomyocytes, principal enzyme converts triglycerides free acids and glycerol, increases infarction (MI). Cardiomyocyte-specific LPL deficiency enhanced cardiac dysfunction apoptosis following MI. Deficiency of aquaporin 7 (AQP7), glycerol channel increased infarct size response ischemia. Ischemic conditions activated glycerol-3-phosphate dehydrogenase 2 (GPD2), which into dihydroxyacetone phosphate facilitate adenosine triphosphate (ATP) synthesis from glycerol. Conversely, GPD2 exacerbated after acute Moreover, cardiomyocyte-specific suppressed effectiveness peroxisome proliferator-activated receptor alpha (PPARα) agonist treatment for MI-induced dysfunction. These results suggest LPL/AQP7/GPD2-mediated plays an important role preventing ischemia-related damage.