Aging impairs insulin-stimulated glucose uptake in rat skeletal muscle via suppressing AMPKα

Wan, Qiang; Wei-qiang, Kang; Zhu, Qing; Zhang, Pengju; Liu, Yi

doi:10.1038/emm.2007.59

Cited by 107 publications

(101 citation statements)

References 37 publications

(50 reference statements)

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“…Glycemia was high at 9 months of age in all groups (Table 1) compared to 3-month-old mice [5]; this age-dependent increase in circulating glucose has been reported in rat [55], monkey [41], and human [3].…”

Section: Resultssupporting

confidence: 56%

Postnatal exposure to voluntary exercise but not the antioxidant catechin protects the vasculature after a switch to an atherogenic environment in middle-age mice

Leblond

Nguyen

Bolduc

et al. 2013

Pflugers Arch - Eur J Physiol

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We aimed to evaluate the lasting functional imprinting of exercise (EX) and catechin (CAT) on the vascular function of middle-age mice switched to a proatherogenic environment. C57BL/6J mice (n=10-15 in each group) fed a regular diet (RD) were exposed from the age of 1 to 9 months either to EX (voluntary running; 2.7± 0.2 km/day), to the polyphenol CAT (30 mg/kg/day in drinking water), or to physical inactivity (PI). At 9 months of age, EX and CAT were stopped and mice either remained on the RD or were fed a Western diet (WD) for an additional 3 months. At 12 months of age, mice from all groups fed a WD had similar body mass, systolic blood pressure, and plasma total cholesterol, glucose, insulin, and isoprostane. Compared to the RD, the WD induced an indomethacin-sensitive aortic endothelium-dependent and independent dysfunction in PI mice (p<0.05) that was prevented by both EX and CAT; this benefit was associated with a higher (p< 0.05) non-nitric oxide/non-prostacyclin endothelium-dependent relaxation. While EX, but not PI or CAT, prevented vascular dysfunction induced by the WD in cerebral arteries, it had no effect in femoral arteries. The profiles of activity of antioxidant enzymes and of proinflammatory gene expression in the aorta suggest a better adaptation of EX>CAT>PI mice to stress. In conclusion, our data suggest that a postnatal exposure to EX, but not to CAT, imprints an adaptive defense capacity in the vasculature against a deleterious change in lifestyle.Correspondence to: Eric Thorin.eric.thorin@umontreal.ca. Electronic supplementary material The online version of this article

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Section: Resultssupporting

confidence: 56%

Postnatal exposure to voluntary exercise but not the antioxidant catechin protects the vasculature after a switch to an atherogenic environment in middle-age mice

Leblond

Nguyen

Bolduc

et al. 2013

Pflugers Arch - Eur J Physiol

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“…Among the many activators of PGC-1, AMP-activated kinase (AMPK) seems to be the most crucial for regulating mitochondrial metabolism and biogenesis. Reduced AMPK activity has been reported in aged animals and is directly linked to age-related insulin resistance and impaired fatty-acid oxidation (Qiang et al, 2007;Reznick et al, 2007). Collectively, these studies indicate that alterations in mitochondrial dynamics are a key component of the mitochondrial adaptations that occur in response to mitochondrial biogenesis.…”

Section: Journal Of Cell Sciencementioning

confidence: 75%

New insights into the role of mitochondria in aging: mitochondrial dynamics and more

Seo

Joseph

Dutta

et al. 2010

Journal of Cell Science

460

366

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SummaryA decline in mitochondrial function plays a key role in the aging process and increases the incidence of age-related disorders. A deeper understanding of the intricate nature of mitochondrial dynamics, which is described as the balance between mitochondrial fusion and fission, has revealed that functional and structural alterations in mitochondrial morphology are important factors in several key pathologies associated with aging. Indeed, a recent wave of studies has demonstrated the pleiotropic role of fusion and fission proteins in numerous cellular processes, including mitochondrial metabolism, redox signaling, the maintenance of mitochondrial DNA and cell death. Additionally, mitochondrial fusion and fission, together with autophagy, have been proposed to form a quality-maintenance mechanism that facilitates the removal of damaged mitochondria from the cell, a process that is particularly important to forestall aging. Thus, dysfunctional regulation of mitochondrial dynamics might be one of the intrinsic causes of mitochondrial dysfunction, which contributes to oxidative stress and cell death during the aging process. In this Commentary, we discuss recent studies that have converged at a consensus regarding the involvement of mitochondrial dynamics in key cellular processes, and introduce a possible link between abnormal mitochondrial dynamics and aging. Journal of Cell Science (Chen and Chan, 2009). However, the relevance of mitochondrial fusion and fission to underlying mechanisms of aging has not been fully appreciated, in part because the molecular events that underlie the aging process have not yet been completely elucidated. In this Commentary, we discuss current knowledge of mitochondrial dynamics, structure and function in relation to key cellular events, including mitochondrial biogenesis, mtDNA homeostasis, autophagy and cell death. By providing a basic overview of mitochondrial fusion and fission events and their general function in these crucial biological processes during normal stable environmental conditions, we hope to portray how alterations in mitochondrial dynamics can contribute to the mitochondrial dysfunction that is commonly associated with aging. Mechanisms underlying mitochondrial dynamicsMitochondria are highly complex and dynamic organelles that can alter their organization, shape and size, depending on intracellular and extracellular signals (Bereiter-Hahn and Voth, 1994;Rube and van der Bliek, 2004). Mitochondria undergo a continuous cycle of fusion and fission, and the balance between these opposing events determines the morphology of the organelle (Chen and Chan, 2004) (Fig. 2). Whereas decreased fusion can result in mitochondrial fragmentation because of excessive fission, decreased fission can generate long and highly interconnected mitochondria (Sesaki and Jensen, 1999).During the past decade, various cellular components have been identified as key mediators of mitochondrial fusion and fission in yeast (Hoppins et al., 2007;Merz et al., 2007;Okamoto and Shaw, 2005). The...

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“…ing aging (44,46) and an involvement of AMPK in the regulation of aging processes (reviewed in Ref. 52).…”

Section: E499 Uncoupling-induced Longevity and Redox Signalingmentioning

confidence: 99%

Skeletal muscle uncoupling-induced longevity in mice is linked to increased substrate metabolism and induction of the endogenous antioxidant defense system

Keipert

Ost

Chadt

et al. 2013

American Journal of Physiology-Endocrinology and Metabolism

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Keipert S, Ost M, Chadt A, Voigt A, Ayala V, Portero-Otin M, Pamplona R, Al-Hasani H, Klaus S. Skeletal muscle uncouplinginduced longevity in mice is linked to increased substrate metabolism and induction of the endogenous antioxidant defense system. Am J Physiol Endocrinol Metab 304: E495-E506, 2013. First published December 31, 2012 doi:10.1152/ajpendo.00518.2012.-Ectopic expression of uncoupling protein 1 (UCP1) in skeletal muscle (SM) mitochondria increases lifespan considerably in high-fat diet-fed UCP1 Tg mice compared with wild types (WT). To clarify the underlying mechanisms, we investigated substrate metabolism as well as oxidative stress damage and antioxidant defense in SM of low-fatand high-fat-fed mice. Tg mice showed an increased protein expression of phosphorylated AMP-activated protein kinase, markers of lipid turnover (p-ACC, FAT/CD36), and an increased SM ex vivo fatty acid oxidation. Surprisingly, UCP1 Tg mice showed elevated lipid peroxidative protein modifications with no changes in glycoxidation or direct protein oxidation. This was paralleled by an induction of catalase and superoxide dismutase activity, an increased redox signaling (MAPK signaling pathway), and increased expression of stress-protective heat shock protein 25. We conclude that increased skeletal muscle mitochondrial uncoupling in vivo does not reduce the oxidative stress status in the muscle cell. Moreover, it increases lipid metabolism and reactive lipid-derived carbonyls. This stress induction in turn increases the endogenous antioxidant defense system and redox signaling. Altogether, our data argue for an adaptive role of reactive species as essential signaling molecules for health and longevity.uncoupling protein 1; AMP-activated protein kinase; oxidative stress; redox signaling; lipid metabolism AGING IS A VERY COMPLEX PROCESS driven by numerous molecular pathways and biochemical events. Regarding the relationship between energy metabolism and longevity, there is a hypothesis termed "uncoupling to survive," which suggests that increased mitochondrial uncoupling and thus increased energy expenditure might increase longevity by preventing the formation of reactive oxygen species (ROS) (6). Previously, we showed that transgenic (Tg) mice with an ectopic expression of the uncoupling protein 1 (UCP1) in skeletal muscle (UCP1 Tg mice) showed a delayed development of obesity, improved glucose tolerance, and a 42% increased median lifespan compared with their wild-type (WT) littermates when exposed to a high-fat diet (30). However, the molecular mechanisms for these beneficial health effects of skeletal muscle uncoupling are not yet clarified.One hallmark of UCP1 Tg mice is an increased insulin sensitivity independent of body weight. Insulin resistance plays a crucial part in the pathogenesis of the metabolic syndrome and is characterized by a reduced substrate metabolism and impaired defense against stress in skeletal muscle. Skeletal muscle (SM) uncoupling increases SM glucose uptake and activates the AMPactivated protein k...

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Aging impairs insulin-stimulated glucose uptake in rat skeletal muscle via suppressing AMPKα

Cited by 107 publications

References 37 publications

Postnatal exposure to voluntary exercise but not the antioxidant catechin protects the vasculature after a switch to an atherogenic environment in middle-age mice

Postnatal exposure to voluntary exercise but not the antioxidant catechin protects the vasculature after a switch to an atherogenic environment in middle-age mice

New insights into the role of mitochondria in aging: mitochondrial dynamics and more

Skeletal muscle uncoupling-induced longevity in mice is linked to increased substrate metabolism and induction of the endogenous antioxidant defense system

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