Age-Related Changes in Intramyocellular Lipid in Humans by in vivo &lt;sup&gt;1&lt;/sup&gt;H-MR Spectroscopy

Nakagawa, Yoku; Hattori, Masa Aki; Harada, Kuniaki; Shirase, Ryuji; Bando, Michio; Okano, Goroh

doi:10.1159/000100869

Cited by 62 publications

(58 citation statements)

References 42 publications

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“…Studies that improved insulin sensitivity by low-calorie diets in patients with T2D were accompanied by a reduction in IMTG content (Jazet et al 2008, Lara-Castro et al 2008. Insulin resistance associated with ageing (Nakagawa et al 2007), growth hormone administration (Krag et al 2007) and post-burn trauma (Cree & Wolfe 2008) has been reported to be associated with increased IMTG content. Current opinion is reasonably clear on the fact that IMTG is a useful marker of the level of cytosolic lipid accumulation, but it is more likely that active lipid metabolites such as LCACoAs, DAGs and ceramides or intermediates of FA oxidation pathways interfere with insulin action via a variety of potential mechanisms (Fig.…”

Section: Linking Intramyocellular Triglyceride Content and Insulin Acmentioning

confidence: 99%

Fatty acid metabolism, energy expenditure and insulin resistance in muscle

Turner¹,

Cooney²,

Kraegen³

et al. 2013

Journal of Endocrinology

167

120

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Fatty acids (FAs) are essential elements of all cells and have significant roles as energy substrates, components of cellular structure and signalling molecules. The storage of excess energy intake as fat in adipose tissue is an evolutionary advantage aimed at protecting against starvation, but in much of today's world, humans are faced with an unlimited availability of food, and the excessive accumulation of fat is now a major risk for human health, especially the development of type 2 diabetes (T2D). Since the first recognition of the association between fat accumulation, reduced insulin action and increased risk of T2D, several mechanisms have been proposed to link excess FA availability to reduced insulin action, with some of them being competing or contradictory. This review summarises the evidence for these mechanisms in the context of excess dietary FAs generating insulin resistance in muscle, the major tissue involved in insulin-stimulated disposal of blood glucose. It also outlines potential problems with models and measurements that may hinder as well as help improve our understanding of the links between FAs and insulin action. (C:18:0), oleic acid (C18:1n-9), linoleic acid (C18:2n-6) and, particularly in smaller mammals, arachidonic acid (20:4n-6) and docosahexaenoic acid (22:6n-3). These FAs are the major components of storage triglycerides and cellular membranes, and although C16-C18 FAs are also components of some of the FA-derived signalling molecules (diacylglycerols (DAGs) and ceramides), many of the major lipid signalling molecules (prostaglandins and leukotrienes) are synthesised from very-long-chain, unsaturated FAs (e.g. arachidonic and docosahexaenoic acids) ( Kruger et al. 2010).In the context of the links between excessive lipid storage (obesity) and reduced insulin action (insulin Journal of EndocrinologyThematic Review N TURNER and others Fatty acids and insulin action 220:2 T61-T79

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Section: Linking Intramyocellular Triglyceride Content and Insulin Acmentioning

confidence: 99%

Fatty acid metabolism, energy expenditure and insulin resistance in muscle

Turner¹,

Cooney²,

Kraegen³

et al. 2013

Journal of Endocrinology

167

120

View full text Add to dashboard Cite

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“…However, it is important to realize that there are other abnormalities occurring in aged skeletal muscle. Other common phenotypical traits include, but are not limited to, increased intramuscular triglyceride (IMTG) accumulation, 55,56 insulin resistance, 57 and a reduced myofiber regenerative potential. 58 Although these factors were not measured in the present study, it is worth mentioning that several of the novel observations made in the present study may be relevant to these additional age-associated muscle alterations.…”

Section: Atrophy and Hypertrophy Signaling In Sarcopenia 171mentioning

confidence: 99%

Human Sarcopenia Reveals an Increase in SOCS-3 and Myostatin and a Reduced Efficiency of Akt Phosphorylation

Léger

Derave

Bock

et al. 2008

Rejuvenation Research

242

175

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Age-related skeletal muscle sarcopenia is linked with increases in falls, fractures, and death and therefore has important socioeconomic consequences. The molecular mechanisms controlling age-related muscle loss in humans are not well understood, but are likely to involve multiple signaling pathways. This study investigated the regulation of several genes and proteins involved in the activation of key signaling pathways promoting muscle hypertrophy, including GH/STAT5, IGF-1/Akt/GSK-3␤/4E-BP1, and muscle atrophy, including TNF␣/ SOCS-3 and Akt/FKHR/atrogene, in muscle biopsies from 13 young (20 ؎ 0.2 years) and 16 older (70 ؎ 0.3 years) males. In the older males compared to the young subjects, muscle fiber cross-sectional area was reduced by 40-45% in the type II muscle fibers. TNF␣ and SOCS-3 were increased by 2.8 and 1.5 fold, respectively. Growth hormone receptor protein (GHR) and IGF-1 mRNA were decreased by 45%. Total Akt, but not phosphorylated Akt, was increased by 2.5 fold, which corresponded to a 30% reduction in the efficiency of Akt phosphorylation in the older subjects. Phosphorylated and total GSK-3␤ were increased by 1.5 and 1.8 fold, respectively, while 4E-BP1 levels were not changed. Nuclear FKHR and FKHRL1 were decreased by 73 and 50%, respectively, with no changes in their atrophy target genes, atrogin-1 and MuRF1. Myostatin mRNA and protein levels were significantly elevated by 2 and 1.4 fold. Human sarcopenia may be linked to a reduction in the activity or sensitivity of anabolic signaling proteins such as GHR, IGF-1, and Akt. TNF␣, SOCS-3, and myostatin are potential candidates influencing this anabolic perturbation. 163

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“…16 Magnetic resonance images were acquired using a clinical 1.5-T whole-body scanner system (Signa Horizon LX, GE Medical Systems, Milwaukee, WI, USA), and a standard head coil (28 cm diameter) was used for detection. Transverse T 1 -weighed magnetic resonance images (echo time/repetition time¼8.5/400 ms) were acquired to determine the placement of the proton-MRS voxels.…”

Section: Imcl Content By Proton-mrsmentioning

confidence: 99%

“…IMCL and extramyocellular lipid were quantified relative to muscle water as described previously. 16 …”

Section: Imcl Content By Proton-mrsmentioning

confidence: 99%

Lower aerobic capacity was associated with abnormal intramuscular energetics in patients with metabolic syndrome

et al. 2011

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Lower aerobic capacity is a strong and independent predictor of cardiovascular morbidity and mortality in patients with metabolic syndrome (MetS). However, the mechanisms are not fully elucidated. We tested the hypothesis that skeletal muscle dysfunction could contribute to the lower aerobic capacity in MetS patients. The incremental exercise tests with cycle ergometer were performed in 12 male patients with MetS with no habitual exercise and 11 age-, sex-and activity-matched control subjects to assess the aerobic capacity. We performed 31 phosphorus-magnetic resonance spectroscopy (MRS) to assess the high-energy phosphate metabolism in skeletal muscle during aerobic exercise. Proton-MRS was also performed to measure intramyocellular lipid (IMCL) content. Peak oxygen uptake (peak VO 2 ; 34.1±6.2 vs. 41.4±8.4 ml kg À1 min À1 , Po0.05) and anaerobic threshold (AT; 18.0±2.4 vs. 23.1±3.7 ml kg À1 min À1 , Po0.01) adjusted by lean body mass were lower in MetS patients than control subjects. Phosphocreatine (PCr) loss during exercise was 1.5-fold greater in MetS, suggesting reduced intramuscular oxidative capacity. PCr loss was inversely correlated with peak VO 2 (r¼À0.64) and AT (r¼À0.60), respectively. IMCL content was threefold higher in MetS and was inversely correlated with peak VO 2 (r¼À0.47) and AT (r¼À0.52), respectively. Moreover, there was a positive correlation between IMCL content and PCr loss (r¼0.64). These results suggested that lean-body aerobic capacity in MetS patients was lower compared with activity-matched healthy subjects, which might be due to the reduced intramuscular fatty acid oxidative metabolism.

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Age-Related Changes in Intramyocellular Lipid in Humans by in vivo <sup>1</sup>H-MR Spectroscopy

Cited by 62 publications

References 42 publications

Fatty acid metabolism, energy expenditure and insulin resistance in muscle

Fatty acid metabolism, energy expenditure and insulin resistance in muscle

Human Sarcopenia Reveals an Increase in SOCS-3 and Myostatin and a Reduced Efficiency of Akt Phosphorylation

Lower aerobic capacity was associated with abnormal intramuscular energetics in patients with metabolic syndrome

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