Regular Exercise in Drosophila Prevents Age-Related Cardiac Dysfunction Caused by High Fat and Heart-Specific Knockdown of skd

Abstract

Skuld (skd) is a subunit of the Mediator complex subunit complex. In the heart, skd controls systemic obesity, is involved in systemic energy metabolism, and is closely linked to cardiac function and aging. However, it is unclear whether the effect of cardiac skd on cardiac energy metabolism affects cardiac function. We found that cardiac-specific knockdown of skd showed impaired cardiac function, metabolic impairment, and premature aging. Drosophila was subjected to an exercise and high-fat diet (HFD) intervention to explore the effects of exercise on cardiac skd expression and cardiac function in HFD Drosophila. We found that Hand-Gal4 > skd RNAi (KC) Drosophila had impaired cardiac function, metabolic impairment, and premature aging. Regular exercise significantly improved cardiac function and metabolism and delayed aging in HFD KC Drosophila. Thus, our study found that the effect of skd on cardiac energy metabolism in the heart affected cardiac function. Exercise may counteract age-related cardiac dysfunction and metabolic disturbances caused by HFD and heart-specific knockdown of skd. Skd may be a potential therapeutic target for heart disease.

Physical exercise ameliorates age‐related deterioration of skeletal muscle and mortality by activating Pten‐related pathways in Drosophila on a high‐salt diet

“…In Drosophila, a 5-day high-fat diet(30% coconut oil) can induce an obese phenotype, accompanied by reduced exercise capacity, weakened heart function, and shortened lifespan, which is associated with increased triglyceride levels, increased lipid oxidation toxicity, and abnormal changes in genes related to lipid metabolism pathways (such as bmm and foxo genes). 46,56,57 4 days of strict high-salt intake (4%NaCl) significantly shortened the lifespan of flies. 58 4 weeks of high-salt intake(2%NaCl) accelerates age-related defects of heart, and these defects included a marked increase in arrhythmia index and a decrease in fractional shortening and the number of mitochondria and myofibrils.…”

“…43 Exercise as a health promotion strategy can effectively improve aging and a HSD-induced sarcopenia, high blood pressure, and heart disease. 3,16,[44][45][46] In flies, a HSD induces the age-related decline in climbing ability, heart function, and skeletal muscle and heart structure damage, and it also reduces the lifespan of flies, and its molecular mechanism is related to FOXO pathway, salt gene expression, and oxidative stress. 16,27,28 However, the molecular mechanism of salt-induced age-related sarcopenia and the mechanism of exercise against salt-induced age-related sarcopenia remain unclear.…”

“…In addition, flies are also conservative in response to some dietary interventions. In Drosophila , a 5‐day high‐fat diet(30% coconut oil) can induce an obese phenotype, accompanied by reduced exercise capacity, weakened heart function, and shortened lifespan, which is associated with increased triglyceride levels, increased lipid oxidation toxicity, and abnormal changes in genes related to lipid metabolism pathways (such as bmm and foxo genes) 46,56,57 . 4 days of strict high‐salt intake (4%NaCl) significantly shortened the lifespan of flies 58 .…”

“…Aging of blood vessels is accompanied by an increase in blood pressure, and high salt intake can promote the age‐related increase in blood pressure 43 . Exercise as a health promotion strategy can effectively improve aging and a HSD‐induced sarcopenia, high blood pressure, and heart disease 3,16,44–46 . In flies, a HSD induces the age‐related decline in climbing ability, heart function, and skeletal muscle and heart structure damage, and it also reduces the lifespan of flies, and its molecular mechanism is related to FOXO pathway, salt gene expression, and oxidative stress 16,27,28 .…”

Effects of hypoxic compound exercise to promote HIF‐1α expression on cardiac pumping function, sleep activity behavior, and exercise capacity in Drosophila

“…qPCR amplification reactions were replicated, thermocycled, and fluoresced three times using an ABI7300 real‐time PCR instrument (Applied Biosystems, USA): (30 s at 95°C, 5 s at 95°C, and 30 s at 60°C) × 40. rp49/u6 standard SYBR Green (Takara) for real‐time PCR. The relative abundance of the measured genes was calculated by the 2 −ΔΔCt method and normalized with GAPDH 33 . The constitutive ribosomal gene rp49 is often used as an endogenous control in Drosophila gene expression experiments, so we used the rp49 gene as an internal reference gene.…”