IKK/NF-κB regulates skeletal myogenesis via a signaling switch to inhibit differentiation and promote mitochondrial biogenesis

Bakkar, Nadine; Wang, Jingxin; Ladner, Katherine J.; Wang, Huating; Dahlman, Jason M.; Carathers, Micheal; Acharyya, Swarnali; Rudnicki, Michael A.; Hollenbach, Andrew D.; Guttridge, Denis C.

doi:10.1083/jcb.20070717908082013c

Cited by 76 publications

(42 citation statements)

References 64 publications

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“…) and promoters of mitochondria biogenesis (Bakkar et al . ). Although the mechanism remains unknown, expression of some of these inhibitors is activated by PPARGC1A overexpression (Liang et al .…”

Section: Resultsmentioning

confidence: 97%

Transcriptional analysis of intramuscular fatty acid composition in the longissimus thoracis muscle of Iberian × Landrace back‐crossed pigs

et al. 2013

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This study aimed at identifying differential gene expression conditional on the fatty acid profile of the longissimus thoracis (Lt) muscle, a prime cut of economic relevance for fresh and cured pork production. A population of 110 Iberian (25%) × Landrace (75%) back-crossed pigs was used, because these two breeds exhibit extreme profiles of intramuscular saturated fatty acid, monounsaturated fatty acid (MUFA) and polyunsaturated fatty acid (PUFA) contents. Total RNA from Lt muscle was individually hybridized to GeneChip Porcine Genome arrays (Affymetrix). A principal component analysis was performed with data from the 110 animals to select 40 extreme animals based on the total fatty acid profile and the MUFA composition (MAP). Comparison of global transcription levels between extreme fatty acid profile pigs (n = 40) resulted in 219 differentially expressed probes (false discovery rate <0.10). Gene ontology, pathway and network analysis indicated that animals with higher percentages of PUFA exhibit a shift toward a more oxidative muscular metabolism state, with a raise in mitochondria function (PPARGC1A, ATF2), fatty acid uptake and oxidation (FABP5, MGLL). On the other hand, 87 probes were differentially expressed between MUFA composition groups (n = 40; false discovery rate <0.10). In particular, muscles rich in n-7 MUFA expressed higher levels of genes involved in lipid metabolism (GLUL, CRAT, PLA2G15) and lower levels of fatty acid elongation genes (ELOVL5). Moreover, the chromosomal position of FABP5, PAQR3, MGLL, PPARGC1A, GLUL and ELOVL5 co-localized with very relevant QTL for fat deposition and composition described in the same resource population. This study represents a complementary approach to identifying genes underlying these QTL effects.

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Section: Resultsmentioning

confidence: 97%

Transcriptional analysis of intramuscular fatty acid composition in the longissimus thoracis muscle of Iberian × Landrace back‐crossed pigs

et al. 2013

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“…Although protein degradation was not directly analysed in this study, the observations point to a potentially important role for FOXO in the programming effect in skeletal muscle following early‐life nutrient stress. NF‐κB's signalling has also been shown to be involved in atrophy of skeletal muscle via protein degradation (reviewed in Jackman & Kandarian, ; Bakkar et al ., ), but also plays a role in early muscle cell survival where NF‐κB inhibition in the presence of an apoptotic dose of tumour necrosis factor‐α (TNF‐α) exacerbates cell death (Stewart et al ., ). Furthermore, as both NF‐κB and FOXO have been linked with cell survival instead of growth, that is, shifting cellular function towards oxidative stress resistance and DNA repair (Brunet et al ., ; Greer & Brunet, ; Wang et al ., ), and are associated with lifespan extension (Giannakou et al ., ; Alic et al ., ), these molecules could be fundamental in programming and perhaps memory, particularly impacting in later life where impaired DNA repair and oxidative stress are linked with the muscle loss and sarcopenia (reviewed in Jackson & McArdle, ).…”

Section: Emergence Of Evidence For Skeletal Muscle Memorymentioning

confidence: 99%

Does skeletal muscle have an ‘epi’‐memory? The role of epigenetics in nutritional programming, metabolic disease, aging and exercise

2016

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SummarySkeletal muscle mass, quality and adaptability are fundamental in promoting muscle performance, maintaining metabolic function and supporting longevity and healthspan. Skeletal muscle is programmable and can ‘remember’ early‐life metabolic stimuli affecting its function in adult life. In this review, the authors pose the question as to whether skeletal muscle has an ‘epi’‐memory? Following an initial encounter with an environmental stimulus, we discuss the underlying molecular and epigenetic mechanisms enabling skeletal muscle to adapt, should it re‐encounter the stimulus in later life. We also define skeletal muscle memory and outline the scientific literature contributing to this field. Furthermore, we review the evidence for early‐life nutrient stress and low birth weight in animals and human cohort studies, respectively, and discuss the underlying molecular mechanisms culminating in skeletal muscle dysfunction, metabolic disease and loss of skeletal muscle mass across the lifespan. We also summarize and discuss studies that isolate muscle stem cells from different environmental niches in vivo (physically active, diabetic, cachectic, aged) and how they reportedly remember this environment once isolated in vitro. Finally, we will outline the molecular and epigenetic mechanisms underlying skeletal muscle memory and review the epigenetic regulation of exercise‐induced skeletal muscle adaptation, highlighting exercise interventions as suitable models to investigate skeletal muscle memory in humans. We believe that understanding the ‘epi’‐memory of skeletal muscle will enable the next generation of targeted therapies to promote muscle growth and reduce muscle loss to enable healthy aging.

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“…This finding is consistent with the well-supported role for NF-kB as a negative regulator of myogenesis. 9,23,24 Further support that suppression of NF-kB activity promoted their myogenic fusion was noted when we were unable to identify GFP-positive HPPs in the d.n. IKKb condition following 96 h of pericyte/myotube co-culture.…”

Section: Nf-kb Affects the Myogenic Potential Of Hppsmentioning

confidence: 70%

NF‐KB activity functions in primary pericytes in a cell‐ and non‐cell‐autonomous manner to affect myotube formation

2013

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IKK/NF-κB regulates skeletal myogenesis via a signaling switch to inhibit differentiation and promote mitochondrial biogenesis

Abstract: Figure 3. (F) Primary or C2C12 myoblasts were transfected with siControl (siCont) or siRNA against p65 (sip65) along with Tn-luc reporter. Cells were switched to DM, and luciferase assays were performed. Error bars represent SEM.

Cited by 76 publications

References 64 publications

Transcriptional analysis of intramuscular fatty acid composition in the longissimus thoracis muscle of Iberian × Landrace back‐crossed pigs

Transcriptional analysis of intramuscular fatty acid composition in the longissimus thoracis muscle of Iberian × Landrace back‐crossed pigs

Does skeletal muscle have an ‘epi’‐memory? The role of epigenetics in nutritional programming, metabolic disease, aging and exercise

NF‐KB activity functions in primary pericytes in a cell‐ and non‐cell‐autonomous manner to affect myotube formation

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