Effects of intermittent ladder-climbing exercise training on mitochondrial biogenesis and endoplasmic reticulum stress of the cardiac muscle in obese middle-aged rats

ABSTRACT Ubiquitin conjugation typically requires three classes of enzyme: E1, E2, and E3. A fourth type of enzyme (E4), however, was recently shown to be required for the degradation of certain types of substrate in yeast. We previously identified UFD2a (also known as E4B) as an E4 in mammals. UFD2a is exclusively expressed in cardiac muscle during mouse embryonic development, but it is abundant in neurons of adult mice and is implicated in the pathogenesis of neurodegenerative disease. The precise physiological function of this enzyme has remained largely unknown, however. Here, we show that mice lacking UFD2a die in utero, manifesting marked apoptosis in the developing heart. Polyubiquitylation activity for an E4 substrate was greatly reduced in Ufd2a −/− mouse embryonic fibroblasts. Furthermore, Ufd2a +/− mice displayed axonal dystrophy in the nucleus gracilis, as well as degeneration of Purkinje cells accompanied by endoplasmic reticulum stress. These animals also developed a neurological disorder. UFD2a thus appears to be essential for the development of cardiac muscle, as well as for the protection of spinocerebellar neurons from degeneration induced by endoplasmic reticulum stress.

Download Full-text

Late-onset caloric restriction alters skeletal muscle metabolism by modulating pyruvate metabolism

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00508.2014 ◽

2015 ◽

Vol 308 (11) ◽

pp. E942-E949 ◽

Cited By ~ 11

Author(s):

Chiao-nan (Joyce) Chen ◽

Shang-Ying Lin ◽

Yi-Hung Liao ◽

Zhen-jie Li ◽

Alice May-Kuen Wong

Keyword(s):

Energy Metabolism ◽

Muscle Mass ◽

Mitochondrial Biogenesis ◽

Muscle Metabolism ◽

Muscle Loss ◽

Aged Rats ◽

Middle Aged ◽

Pyruvate Metabolism ◽

Age Related ◽

Age Dependent

Caloric restriction (CR) attenuates age-related muscle loss. However, the underlying mechanism responsible for this attenuation is not fully understood. This study evaluated the role of energy metabolism in the CR-induced attenuation of muscle loss. The aims of this study were twofold: 1) to evaluate the effect of CR on energy metabolism and determine its relationship with muscle mass, and 2) to determine whether the effects of CR are age dependent. Young and middle-aged rats were randomized into either 40% CR or ad libitum (AL) diet groups for 14 wk. Major energy-producing pathways in muscles, i.e., glycolysis and mitochondrial oxidative phosphorylation (OXPHOS), were examined. We found that the effects of CR were age dependent. CR improved muscle metabolism and normalized muscle mass in middle-aged animals but not young animals. CR decreased glycolysis and increased the cellular dependency for OXPHOS vs. glycolysis in muscles of middle-aged rats, which was associated with the improvement of normalized muscle mass. The metabolic reprogramming induced by CR was related to modulation of pyruvate metabolism and increased mitochondrial biogenesis. Compared with animals fed AL, middle-aged animals with CR had lower lactate dehydrogenase A content and greater mitochondrial pyruvate carrier content. Markers of mitochondrial biogenesis, including AMPK activation levels and SIRT1 and COX-IV content, also showed increased levels. In conclusion, 14 wk of CR improved muscle metabolism and preserved muscle mass in middle-aged animals but not in young developing animals. CR-attenuated age-related muscle loss is associated with reprogramming of the metabolic pathway from glycolysis to OXPHOS.

Download Full-text

Exercise Training Attenuates Non-Alcoholic Fatty Liver Disease in rats with Diabetes via Endoplasmic Reticulum Stress

Medicine & Science in Sports & Exercise ◽

10.1249/01.mss.0000535794.02833.22 ◽

2018 ◽

Vol 50 (5S) ◽

pp. 215

Author(s):

Junhan Li ◽

Derun Gao ◽

Junzhi Sun ◽

Kai Zou ◽

Quansheng Su

Keyword(s):

Endoplasmic Reticulum ◽

Liver Disease ◽

Exercise Training ◽

Endoplasmic Reticulum Stress ◽

Fatty Liver ◽

Fatty Liver Disease ◽

Alcoholic Fatty Liver ◽

Alcoholic Fatty Liver Disease

Download Full-text

Effects of Methionine Restriction and Exercise Training on Antioxidant Capacity of Cardiac Tissues in Ovariectomized Middle-Aged Rats

Medicine & Science in Sports & Exercise ◽

10.1249/01.mss.0000495689.42979.13 ◽

2014 ◽

Vol 46 ◽

pp. 733

Author(s):

Sian-Ren Yang ◽

Hsin-Yao Cheng ◽

Shiow-Chwen Tsai

Keyword(s):

Exercise Training ◽

Antioxidant Capacity ◽

Aged Rats ◽

Middle Aged ◽

Cardiac Tissues ◽

Methionine Restriction

Download Full-text

Muscle microvascular adaptation and angiogenic gene induction in response to exercise training are attenuated in middle-aged rats

Comparative Exercise Physiology ◽

10.3920/cep150007 ◽

2015 ◽

Vol 11 (1) ◽

pp. 23-33

Author(s):

J. Suzuki

Keyword(s):

Exercise Training ◽

Acute Exercise ◽

Young Group ◽

Treadmill Running ◽

Mrna Levels ◽

Aged Rats ◽

Middle Aged ◽

Vegf Mrna ◽

Aged Group ◽

Exercise Induced

This study was designed to investigate exercise-induced changes in muscle capillarisation, the mRNA expression of angiogenic genes, and microRNA levels in young and middle-aged rats. Rats in the training groups were subjected to treadmill running 5 days a week for 3 weeks. The exercise protocol for the young (12-week old) group was 20-25 m/min, 40-60 min/day with a gradient of 15%, and for the middle-aged (12-month old) group was 18-20 m/min, 40-60 min/day with a gradient of 5%. The enzyme histochemical identification of capillary profiles was performed on cross-sections of gastrocnemius muscle. Total RNA was isolated, reverse transcription was performed, and mRNA and microRNA levels were determined by real-time PCR. The capillary-to-fibre ratio was significantly increased by exercise training in the young group (by 10%), but only slightly in the middle-aged (by 5%) group. Vascular endothecial growth factor (VEGF) mRNA levels were at significantly higher values after acute exercise (1.6-fold) and the 3-week training protocol (1.9-fold) in the young group, but not in the middle-aged group. VEGF protein expression levels were significantly increased after training in the young group only. Endothelial nitric oxide synthase, VEGF-R2 and thrombospondin-1 mRNA levels were significantly lower in the middle-aged group than in the young group. Anti-angiogenic miR-195 levels were significantly enhanced by exercise training in the middle-aged group only. These results indicated that the exercise-induced adaptation of muscle capillarity was attenuated in middle-aged rats, possibly by the lower induction of VEGF and up-regulation of anti-angiogenic miRNA expression.

Download Full-text