Sarcopenia in the aging high-fat fed rat: a pilot study for modeling sarcopenic obesity in rodents

Bollheimer, Leo Cornelius; Buettner, Roland; Pongratz, Georg; Brunner-Ploss, Rita; Hechtl, Christine; Banas, Miriam C.; Singler, Katrin; Hamer, Okka W.; Stroszczynski, Christian; Sieber, Cornel; Fellner, Claudia

doi:10.1007/s10522-012-9405-4

Cited by 49 publications

(44 citation statements)

References 31 publications

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“…Similar results have been reported recently for the muscle volume in a pilot study with Wistar rats [8]. Besides those morphological changes in HFD rats we also found a prolongation of T2 relaxation time in the quadriceps muscle.…”

Section: Discussionsupporting

confidence: 92%

“…Thereby, direct induction of apoptosis, autophagy and proteolysis in the myotubes are proposed mechanisms [7]. Furthermore, fatty acids may also interfere with the glucose-dependent PKB/Akt signaling and the energy-sensing AMPK pathways, leading to deregulation of mitochondrial biogenesis and protein synthesis [8]. Taken together, diets with a high amount of fatty acids appear to be important for the development and progression of an excessive loss of muscle mass.…”

Section: Introductionmentioning

confidence: 99%

“…Up to now, most MR-based studies focused on age-associated changes, obesity or diet-induced changes in cross-sectional studies [12,18,19,20,21,22,23]. Analysis of the T2 relaxation time and the lipid fraction was performed in order to reveal potential nutritional lipotoxic effects that could play a role in decreasing muscle volume, as recently shown in a pilot study [8]. …”

Section: Introductionmentioning

confidence: 99%

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Diet-Induced and Age-Related Changes in the Quadriceps Muscle: MRI and MRS in a Rat Model of Sarcopenia

Fellner

Schick²,

Kob³

et al. 2014

Gerontology

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Background: Knowledge about the molecular pathomechanisms of sarcopenia is still sparse, especially with regard to nutritional risk factors and the subtype of sarcopenic obesity. Objective: The aim of this study was to characterize diet-induced and age-related changes on the quality and quantity of the quadriceps muscle in a rat model of sarcopenia by different magnetic resonance (MR) techniques. Methods: A total of 36 6-month-old male Sprague-Dawley rats were randomly subdivided into 2 groups and received either a high-fat diet (HFD) or a control diet (CD). At the age of 16 months, 15 HFD and 18 CD rats underwent MR at 1.5 T. T1-weighted images as well as T2 relaxation time maps were acquired perpendicular to the long axis of the quadriceps muscles. Maximum cross-sectional area (CSA) of the quadriceps muscle was measured on T1-weighted images, and T2 relaxation times of muscle were assessed in a region without visible intramuscular fat (T2_{lean muscle}) and across the complete CSA (T2_muscle). Furthermore, ¹H-MR spectroscopy was performed to evaluate the relative lipid content of the quadriceps muscles. These measurements were repeated 5 months later in the surviving 8 HFD and 14 CD rats. Results: HFD rats revealed significantly decreased CSA and CSA per body weight (BW) as well as prolonged T2 relaxation times of muscle. A higher weight gain (upper tertile during the first 6 months of diet in CD rats) resulted in a significant change of T2_muscle, but had no relevant impact on CSA. Advancing age up to 21 months led to significantly decreased BW, CSA and CSA/BW, significantly prolonged T2_muscle and T2_{lean muscle} and enlarged lipid content in the quadriceps muscle. Conclusions: In an experimental setting a chronically fat-enriched diet was shown to have a relevant and age-associated influence on both muscle quantity and quality. By translational means the employed MR techniques give rise to the possibility of an early detection and noninvasive quantification of sarcopenia in humans, which is highly relevant for the field of geriatrics.

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Section: Discussionsupporting

confidence: 92%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Diet-Induced and Age-Related Changes in the Quadriceps Muscle: MRI and MRS in a Rat Model of Sarcopenia

Fellner

Schick²,

Kob³

et al. 2014

Gerontology

Self Cite

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“…Physical activity might probably differ between the young and old animals and between the DIO and control groups due to heavier body weight of the DIO animals. The individual physical activity of the animals should be taken into account in further studies as a possible confounder (Bollheimer et al ., 2012). Third, it would have been informative to evaluate the potential interest of nutritional strategies able to counteract muscle lipotoxicity in old DIO rats, for example, short-term caloric restriction, to maintain or improve muscle protein anabolism.…”

Section: Discussionmentioning

confidence: 99%

Muscle ectopic fat deposition contributes to anabolic resistance in obese sarcopenic old rats through eIF2α activation

et al. 2014

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Obesity and aging are characterized by decreased insulin sensitivity (IS) and muscle protein synthesis. Intramuscular ceramide accumulation has been implicated in insulin resistance during obesity. We aimed to measure IS, muscle ceramide level, protein synthesis, and activation of intracellular signaling pathways involved in translation initiation in male Wistar young (YR, 6-month) and old (OR, 25-month) rats receiving a low- (LFD) or a high-fat diet (HFD) for 10 weeks. A corresponding cellular approach using C2C12 myotubes treated with palmitate to induce intracellular ceramide deposition was taken. A decreased ability of adipose tissue to store lipids together with a reduced adipocyte diameter and a development of fibrosis were observed in OR after the HFD. Consequently, OR fed the HFD were insulin resistant, showed a strong increase in intramuscular ceramide level and a decrease in muscle protein synthesis associated with increased eIF2α phosphorylation. The accumulation of intramuscular lipids placed a lipid burden on mitochondria and created a disconnect between metabolic and regulating pathways in skeletal muscles of OR. In C2C12 cells, palmitate-induced ceramide accumulation was associated with a decreased protein synthesis together with upregulated eIF2α phosphorylation. In conclusion, a reduced ability to expand adipose tissues was found in OR, reflecting a lower lipid buffering capacity. Muscle mitochondrial activity was affected in OR conferring a reduced ability to oxidize fatty acids entering the muscle cell. Hence, OR were more prone to ectopic muscle lipid accumulation than YR, leading to decreased muscle protein anabolism. This metabolic change is a potential therapeutic target to counter sarcopenic obesity.

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“…Although obesity is a risk factor for sarcopenia, its pathophysiology is complex, and multiple factors, including lifestyle, endocrine, and immunological factors, can play a role. Moreover, aging is associated with important changes in body composition and metabolism, and there are reports of the presence of sarcopenia and centralized fat in the elderly [41,42] . Obesity contributes to inflammation in MS and diabetes.…”

Section: Acta Pharmacologica Sinica Npgmentioning

confidence: 99%

Non-steroidal anti-inflammatory drugs attenuate the vascular responses in aging metabolic syndrome rats

et al. 2014

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Aim: Metabolic syndrome (MS) and aging are low-grade systemic inflammatory conditions, and inflammation is a key component of endothelial dysfunction. The aim of this study was to investigate the effects of non-steroidal anti-inflammatory drugs (NSAIDs) upon the vascular reactivity in aging MS rats. Methods: MS was induced in young male rats by adding 30% sucrose in drinking water over 6, 12, and 18 months. When the treatment was finished, the blood samples were collected, and aortas were dissected out. The expression of COX isoenzymes and PLA 2 in the aortas was analyzed using Western blot analysis. The contractile responses of aortic rings to norepinephrine (1 μmol/L) were measured in the presence or absence of different NSAIDs (10 μmol/L for each).Results: Serum levels of pro-inflammatory cytokines (IL-6, TNF-α, and IL-1β) in control rats were remained stable during the aging process, whereas serum IL-6 in MS rats were significantly increased at 12 and 18 months. The levels of COX isoenzyme and PLA 2 in aortas from control rats increased with the aging, whereas those in aortas from MS rats were irregularly increased with the highest levels at 6 months. Pretreatment with acetylsalicylic acid (a COX-1 preferential inhibitor), indomethacin (a non-selective COX inhibitor) or meloxicam (a COX-2 preferential inhibitor) decreased NE-induced contractions of aortic rings from MS rats at all the ages, with meloxicam being the most potent. Acetylsalicylic acid also significantly reduced the maximum responses of ACh-induced vasorelaxation of aortic rings from MS rats, but indomethacin and meloxicam had no effect. Conclusion: NSAIDs can directly affect vascular responses in aging MS rats. Understanding the effects of NSAIDs on blood vessels may improve the treatment of cardiovascular diseases and MS in the elders.

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Sarcopenia in the aging high-fat fed rat: a pilot study for modeling sarcopenic obesity in rodents

Cited by 49 publications

References 31 publications

Diet-Induced and Age-Related Changes in the Quadriceps Muscle: MRI and MRS in a Rat Model of Sarcopenia

Diet-Induced and Age-Related Changes in the Quadriceps Muscle: MRI and MRS in a Rat Model of Sarcopenia

Muscle ectopic fat deposition contributes to anabolic resistance in obese sarcopenic old rats through eIF2α activation

Non-steroidal anti-inflammatory drugs attenuate the vascular responses in aging metabolic syndrome rats

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