Endurance exercise resistance to lipotoxic cardiomyopathy is associated with cardiac NAD+/dSIR2/PGC-1α pathway activation in old Drosophila

Deng-Tai Wen; Lan Zheng; Jin-xiu Li; Dan Cheng; Yang Liu; Kai Lu; Wen-qi Hou

doi:10.1242/bio.044719

Endurance exercise resistance to lipotoxic cardiomyopathy is associated with cardiac NAD+/dSIR2/PGC-1α pathway activation in old Drosophila

Biology Open ◽

10.1242/bio.044719 ◽

2019 ◽

Vol 8 (10) ◽

pp. bio044719

Author(s):

Deng-Tai Wen ◽

Lan Zheng ◽

Jin-xiu Li ◽

Dan Cheng ◽

Yang Liu ◽

...

Keyword(s):

Endurance Exercise ◽

Pathway Activation ◽

Lipotoxic Cardiomyopathy

Download Full-text

Activation of cardiac Nmnat/NAD+/SIR2 pathways mediates endurance exercise resistance to lipotoxic cardiomyopathy in aging Drosophila

Journal of Experimental Biology ◽

10.1242/jeb.242425 ◽

2021 ◽

Vol 224 (18) ◽

Author(s):

Deng-tai Wen ◽

Lan Zheng ◽

Kai Lu ◽

Wen-qi Hou

Keyword(s):

Endurance Exercise ◽

High Fat Diet ◽

Molecular Mechanisms ◽

Sod Activity ◽

Pathway Activation ◽

Locomotor Impairment ◽

Mda Content ◽

Exercise Induced ◽

Fractional Shortening ◽

Lipotoxic Cardiomyopathy

ABSTRACT Endurance exercise is an important way to resist and treat high-fat diet (HFD)-induced lipotoxic cardiomyopathy, but the underlying molecular mechanisms are poorly understood. Here, we used Drosophila to identify whether cardiac Nmnat/NAD+/SIR2 pathway activation mediates endurance exercise-induced resistance to lipotoxic cardiomyopathy. The results showed that endurance exercise activated the cardiac Nmnat/NAD+/SIR2/FOXO pathway and the Nmnat/NAD+/SIR2/PGC-1α pathway, including up-regulating cardiac Nmnat, SIR2, FOXO and PGC-1α expression, superoxide dismutase (SOD) activity and NAD+ levels, and it prevented HFD-induced or cardiac Nmnat knockdown-induced cardiac lipid accumulation, malondialdehyde (MDA) content and fibrillation increase, and fractional shortening decrease. Cardiac Nmnat overexpression also activated heart Nmnat/NAD+/SIR2 pathways and resisted HFD-induced cardiac malfunction, but it could not protect against HFD-induced lifespan reduction and locomotor impairment. Exercise improved lifespan and mobility in cardiac Nmnat knockdown flies. Therefore, the current results confirm that cardiac Nmnat/NAD+/SIR2 pathways are important antagonists of HFD-induced lipotoxic cardiomyopathy. Cardiac Nmnat/NAD+/SIR2 pathway activation is an important underlying molecular mechanism by which endurance exercise and cardiac Nmnat overexpression give protection against lipotoxic cardiomyopathy in Drosophila.

Download Full-text