A histochemical and morphological study of skeletal muscle from obese hyperglycaemic ob/ob mice

Abstract

Summary. The histochemical and morphological charactefis= tics of muscles from lean and obese hyperglycaemic ob/ob mice were compared to determine the nature of the low skeletal muscle mass of the latter: Gastrocnemius and biceps brachii muscles from obese ob/ob mice were significantly lighter than those from lean mice; whereas the weights of soleus muscles were not significantly different. The small mass of the biceps brachii muscle resulted from a decrease in diameter of the large glycolytic fast white and fast intermediate fibres and a reduction in the proportion of fast white fibres.The size and frequency of the more oxidative fast red fibres was not different. The histochemical appearance of all fibre types studied from muscles in obese mice was identical to equivalent fibres in lean mice. The fat content of muscles from obese mice was three times greater than in lean mice whereas muscle DNA concentration was similar.Key words: Obese mice, muscle size, fibre type, fibre number, diabetes.Obese hyperglycaemic mice with the ob/ob genome have been used extensively as a model for Type 2 (noninsulin-dependent) diabetes. They are characterized by many abnormalities including hyperphagia, fasting hyperglycaemia, and hyperinsulinaemia. They have fewer insulin receptors and their tissues, particularly muscle, show a marked resistance to the normal metabolic actions of this hormone [1]. Obese mice have similar quantities of total body protein to lean mice [2]. However, extra protein present in their enlarged adipose tissue, liver, and intestine disguises a lower content of skeletal muscle protein [3,4].The smaller amount of muscle could be due to a decrease in the number of muscle fibres, or a reduced volume per fibre, or both. If there were fewer fibres within the muscles of obese mice, it would indicate a difference in pre-natat development compared with lean mice since in mice the majority of muscle fibres are present at or soon after birth [5, 6]-On the other hand, a decrease in the post-natal growth of fibres would be compatible with the other reported metabolic defects in ob/ob mice. Insulin is probably the most important physiological factor regulating the overall protein balance in skeletal muscle [7] since k not only stimulates the uptake of amino-acids and protein synthesis, [8] but also inhibits protein degradation. It is conceivable, therefore, that the inherent resistance of muscles from obese mice to the anabolic effects of insulin [9,10] could facilitate a decrease in the post-natal growth of this tissue. Plasma corticosteroid levels are also elevated in ob/ob mice [11,12] and may cause accelerated protein degradation and diversion of amino-acids into excessive gluconeogenesis [13]. If these metabolic abnormalities in obese mice are responsible for their decreased skeletal muscle mass, one would predict that fast and slow phasic muscles would respond differently, since either st~eptozotocin-induced diabetes [14] or corticosteroid injections in rats [15] cause large glycolytic fibres and fast phasic musc...

Myostatin, activin receptor IIb, and follistatin-like-3 gene expression are altered in adipose tissue and skeletal muscle of obese mice

“…MSTN mRNA levels were also significantly increased in the TA but not the SOL muscle of ob/ob compared with wild-type mice, and in the TA muscle of mice on a high-fat diet compared with mice on a low-fat diet, whereas ActRIIb and FSTL3 mRNA levels were unchanged in either muscle. The higher MSTN mRNA levels are associated with a significantly lower TA muscle mass in ob/ob mice, whereas SOL mass was not significantly different, both of which have been previously reported (5). It is therefore tempting to speculate that the increase in MSTN expression is causally related to the decrease in muscle mass observed in the present study and the decrease in muscle mass and fiber size in ob/ob mice reported previously (5) by either initiating the atrophic cascade or maintaining muscle mass at its new smaller size.…”

Morphological and biochemical alterations of skeletal muscles from the genetically obese (ob/ob) mouse

“…There is compelling evidence that the intramuscular fat content is higher in obese mammals, including rodents, 7,26 than in controls. This raises the possibility that the protein content in muscles from obese animals is lower than that in controls.…”

“…As all the three muscles examined were found to contain a greater proportion of hybrid fibres (a marker of structural remodelling 1 ), it is likely that this shift in the fibre type composition results from a process of structural remodelling associated with the obese condition rather than from a different developmental pattern followed by the muscles from the two animal groups. This contention is supported by data 7,42,43 I IIA IID I+IIA IIA+IIB IIA+IID IIB+IID I+IIA+IIB I+IIA+IID I+IIB+IID IIA+IIB+IID I+IIA+IIB+IID 0 10 Alterations in skeletal muscles of ob/ob mouse JG Kemp et al skeletal muscle phenotype in ob/ob mice do not appear until significant progression of obesity. The greater proportion of hybrid fibres detected in SM and EDL muscles of ob/ob mice, and the range of combinations of MHC isoforms co-expressed in these fibres, suggests a process of fibre type transition is taking place in the direction IIB-IID-IIA.…”

“…This is because, to date, investigations of skeletal muscle characteristics in the ob/ob mouse have been carried out mostly [7][8][9] on hindlimb muscles, such as extensor digitorum longus (EDL) and soleus (SOL), and involved histochemistrybased fibre typing, a method unable to detect fibres expressing the IId/x myosin heavy chain (MHC) isoform (type IID/X fibres) and fibres co-expressing several MHC isoforms (hybrid fibres). 1 In this study, we addressed the aforementioned cognitive gaps by examining, at whole muscle and single fibre level, several morphological and biochemical characteristics of three skeletal muscles, differing with respect to anatomical location, physiological function, and fibre type compositionFsternomastoid (SM) (fast-twitch neck muscle known to assist in head/neck rotation and respiration 10 ), EDL (predominantly fast-twitch hindlimb muscle; locomotor 11 ), and SOL (mixed slow/fast-twitch hindlimb muscle; primarily postural 11,12 )Ffrom adult (18-22 weeks) ob/ob mouse and its lean control.…”

Diabetic State-Induced Activation of Calcium-Activated Neutral Proteinase in Mouse Skeletal Muscle.

“…Several abnormal characteristics of skeletal muscles in diabetic mouse are studied from morphological (Almond and Enser, 1984;Hamilton et al, 1968;Naccarato et al, 1970), chemical (Mayer et al, 1974) and electrophysiological aspects (Grossie, 1982). The male KK-CAy mouse has a genetically predisposed syndrome similar to human type II diabetes mellitus (NIDDM) and includes hyperglycemia, hyperinsulinemia, obesity, and insulin resistance (Kimura et al, 1979).…”