Deficiency of Subsarcolemmal Mitochondria in Obesity and Type 2 Diabetes

In the citing paper

“it has generally been assumed that a reduction in muscle mitochondrial function will result in reductions in whole-body fat oxidative capacity (3–5,42,43).”

In the citing paper

“A number of physiological aspects of aging are also found in obesity and diabetes (Fig. 2) including accumulation of ectopic lipids and lipotoxicity in metabolic organs such as liver, skeletal muscle and heart, as well as decreased mitochondrial number and activity [144–147].”

In the citing paper

“Indeed, mitochondrial dysfunction and/or a reduction in mitochondrial content, as characterised by a fall in oxidative capacity, has been reported in skeletal muscle and adipose tissue from obese and diabetic subjects [8, 9].”

In the citing paper

“Mitochondrial mass is consistently 14–38% lower in muscle in obesity and type 2 diabetes (2–5).”

In the citing paper

“Skeletal muscle from obese humans with or without diabetes is characterized by reduced overall mitochondrial content with evidence of morphological changes similar to those in the animal models (Chomentowski et al., 2011; Kelley et al., 2002; Ritov et al., 2005).”

In the citing paper

“muscle insulin resistance often (but not always [86]) coexists with abnormalities in mitochondrial morphology, reduced NADH:O2 oxidoreductase activity, diminished in vivo rates of ATP synthesis and TCA cycle flux, as well as low expression levels of genes involved in mitochondrial biogenesis and oxidative metabolism [47,49,59,68,78].”

In the citing paper

“In some studies, surrogate markers of mitochondrial content are reduced (7, 9, 14), whereas in others they are not (15, 16).”

In the citing paper

“A number of studies have consistently demonstrated lower oxidative capacity in insulin-resistant subjects (5, 7, 8, 14, 23).”

In the citing paper

“Insulin resistance was associated with less mtDNA in some studies (9, 14) but not in others (15).”

In the citing paper

“Electron microscopic studies have revealed a significant reduction (~40%) in mitochondrial density in skeletal muscle in lean NGT offspring of type 2 diabetic parents, in obese nondiabetic individuals and in T2DM subjects compared to lean insulin-sensitive, age-matched controls [111, 112].”

In the citing paper

“Since, in these studies [112, 120], ETC activity and mitochondrial ATP synthesis rate were related to the amount of mitochondrial protein and/or citrate synthase activity, these observations indicate the existence of a basic functional defect in mitochondrial activity in skeletal muscle of obese insulin-resistant individuals [115].”

In the citing paper

“Ex vivo measurement of electron transport chain activity (ETC) [112] and mitochondrial ATP synthesis in isolated mitochondria [120, 121] have demonstrated a decrease in ETC activity and ATP synthesis in obese insulin-resistant individuals compared to lean insulin-sensitive subjects.”

In the citing paper

“Similarly, in vivo and ex vivo measurements of ATP production capacity have been reported to be reduced in skeletal muscle of T2DM patients compared with ageand body mass index (BMI)-matched controls in some (6, 7) but not in all studies (4, 8).”

In the citing paper

“Studies with transmission electron microscopy revealed reduced numbers of SLM in skeletal muscle of type 2 diabetes and obese subjects associated with reduced electron-transport activity per unit mitochondrial DNA, suggesting functional impairment as well (268).”

In the citing paper

“This possibility is consistent with electron microscopy demonstrating diminished mitochondrial size in obesity and diabetes (116), particularly in subsarcolemmal fractions (114).”

In the citing paper

“Ritov et al. (114) demonstrated that the enzymatic activity of OXPHOS complex I, as assessed by the activity of rotenone-sensitive NADH:O 2 oxidoreductase, was reduced by about 40% in skeletal muscle biopsy samples from individuals with type 2 DM and by 20% in obese individuals.”