Pathophysiological analyses of skeletal muscle in obese type 2 diabetes SDT fatty rats

Abstract

Sarcopenia is the age-related decrease of muscle mass and function. Diabetes and obesity are known to be risk factors that exacerbate sarcopenia, but the underlying mechanism of diabetes-related sarcopenia is still unknown. Obese type 2 diabetes SDT fatty rats show early onset of severe diabetes and there have been no reports on the characteristics of their skeletal muscle. Therefore, pathophysiological analyses were performed for the skeletal muscle in these rats. Diabetic male SDT fatty rats were sacrificed at 8, 16, 24, 32 and 40 weeks of age. Age-matched Sprague Dawley (SD) rats were used as the normal control. In addition to biological blood parameters, the soleus and the extensor digitorum longus muscles were examined for muscle weight, histopathology, and protein synthesis and degradation. Muscle grip strength was also examined. These results revealed that the muscle weights of the SDT fatty rats were significantly decreased from 16 weeks of age. The mean cross-sectional area of muscle fibers in the SDT fatty rats decreased from 24 weeks of age. Increased intramyocellular lipid accumulation, identified by immunohistochemistry for adipophilin and TEM, was observed in the SDT fatty rats from 8 weeks of age. Plasma insulin-like growth factor (IGF)-1 levels and muscle strength in the SDT fatty rats decreased at 24 weeks of age and thereafter. These pathophysiological findings have been reported both in sarcopenia in aged humans and in patients with diabetes. In conclusion, the SDT fatty rat was considered to be a useful model for analysis of diabetes-related sarcopenia.

Relationship between Urinary Liver-Type Fatty Acid-Binding Protein (L-FABP) and Sarcopenia in Spontaneously Diabetic Torii Fatty Rats

“…Furthermore, while decreased muscle protein synthesis was considered to contribute to weakness of both the soleus and EDL muscles in the SDT group, the involvement of muscle protein degradation signaling in muscle depression in the SDT group may be low (Figure 11). Although the results of this study support those of a previous study [14], further studies are needed to investigate the association of FoxOassociated downstream pathways with muscle depression in SDT fatty rats.…”

“…Among the limited models of both DKD and sarcopenia, the spontaneously diabetic Torii (SDT) fatty rat is a unique experimental novel model of T2D with kidney disease and sarcopenia [12][13][14] that mimics the pathophysiology of human T2D. Therefore, the aim of the present study was to elucidate the relationship between urinary L-FABP and sarcopenia using the SDT fatty rat.…”

Muscle‐specific Perilipin2 down‐regulation affects lipid metabolism and induces myofiber hypertrophy

“…In these subjects, we observed that Plin2 accumulation is associated with lower muscle mass and strength and paralleled by increased expression of p53 and atrophy‐related genes such as Atrogin‐1 and MuRF‐1 . In a recent study, obese type 2 diabetes STD fatty rats were reported to have high content of Plin2 and lower CSA in type IIb muscle fibres . However, the role of Plin2 in skeletal muscle homeostasis is still not completely understood.…”

“…type 2 diabetes STD fatty rats were reported to have high content of Plin2 and lower CSA in type IIb muscle fibres. 25 However, the role of Plin2 in skeletal muscle homeostasis is still not completely understood. In the present study, we took advantage of in vivo genetic manipulations to dissect the function of Plin2 in adult muscles.…”

The impact of a high-fat diet in mice is dependent on duration and age, and differs between muscles

“…In a study on obese men and women, the predominant upper-body fat distribution was not associated with a significant impairment of respiratory muscle strength (Magnani and Cataneo, 2007). In the lower leg, however, muscle strength is at least partly attributable to a lower specific tension (maximal muscle force per cross-sectional area) in obese older adults (Choi et al, 2016) and obese adult rodents (Kemmochi et al, 2018;Tallis et al, 2018). Part of the lower specific tension may be caused by a larger volume fraction of IMCL, that may be as high as 5% of the muscle fibre volume in obese individuals (Malenfant et al, 2001).…”