Mitochondrial dysfunction results from oxidative stress in the skeletal muscle of diet-induced insulin-resistant mice

Bonnard, C.; Durand, Annie; Peyrol, S; Chanséaume, Emilie; Chauvin, Marie-Agnès; Morio, Béatrice; Vidal, Hubert; Rieusset, Jennifer

doi:10.1172/jci32601

Cited by 534 publications

(691 citation statements)

References 37 publications

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“…Previous studies in rodent model systems indicate that a maternal high-fat diet decreases mitochondrial electron transport chain enzymes activities and antioxidant defense capacity in skeletal muscle and liver of offspring (Bruce et al, 2009;Shelley et al, 2009;Zhang et al, 2011). Consistently, decreased activities of antioxidative enzymes (SOD, GPx and CAT) and increased MDA levels were also observed in skeletal muscle of HE fetuses, suggesting the failure of ROS defense system and more, which is probably one of the major determinants of mitochondrial function alterations (Bonnard et al, 2008). In addition, several studies have shown mitochondrial dysfunction can affect whole-body metabolism and play an important in the pathophysiology of insulin resistance in offspring of high-fat diet-fed dams (Bonnard et al, 2008;Latouche et al, 2014).…”

Section: Discussionsupporting

confidence: 56%

“…Consistently, decreased activities of antioxidative enzymes (SOD, GPx and CAT) and increased MDA levels were also observed in skeletal muscle of HE fetuses, suggesting the failure of ROS defense system and more, which is probably one of the major determinants of mitochondrial function alterations (Bonnard et al, 2008). In addition, several studies have shown mitochondrial dysfunction can affect whole-body metabolism and play an important in the pathophysiology of insulin resistance in offspring of high-fat diet-fed dams (Bonnard et al, 2008;Latouche et al, 2014). In accordance with previous work (Raipuria et al, 2015), in the current study the fetuses from HE sows had a potential risk for metabolic disorder with higher insulin and triglyceride concentrations in umbilical vein serum compared with fetuses from NE sows.…”

Section: Discussionmentioning

confidence: 66%

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Mitochondrial biogenesis is decreased in skeletal muscle of pig fetuses exposed to maternal high-energy diets

Zou

et al. 2017

Animal

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Mitochondria plays an important role in the regulation of energy homeostasis. Moreover, mitochondrial biogenesis accompanies skeletal myogenesis, and we previously reported that maternal high-energy diet repressed skeletal myogenesis in pig fetuses. Therefore, the aim of this study was to evaluate the effects of moderately increased maternal energy intake on skeletal muscle mitochondrial biogenesis and function of the pig fetuses. Primiparous purebred Large White sows were allocated to a normal energy intake group (NE) as recommended by the National Research Council (NRC) and a high energy intake group (HE, 110% of NRC recommendations). On day 90 of gestation, fetal umbilical vein blood and longissimus (LM) muscle were collected. Results showed that the weight gain of sows fed HE diet was higher than NE sows on day 90 of gestation ( P < 0.05). Maternal HE diet increased fetal umbilical vein serum triglyceride and insulin concentrations ( P < 0.05), and tended to increase the homeostasis model assessment index ( P = 0.08). Furthermore, HE fetuses exhibited increased malondialdehyde concentration ( P < 0.05), and decreased activities of antioxidative enzymes ( P < 0.05) and intracellular NAD + level ( P < 0.05) in LM muscle. These alterations in metabolic traits of HE fetuses were accompanied by reduced mitochondrial DNA amount ( P < 0.05) and down-regulated messenger RNA expression levels of genes responsible for mitochondrial biogenesis and function ( P < 0.05). Our results suggest that moderately increased energy supply during gestation decreases mitochondrial biogenesis, function and antioxidative capacity in skeletal muscle of pig fetuses.

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Section: Discussionsupporting

confidence: 56%

Section: Discussionmentioning

confidence: 66%

Mitochondrial biogenesis is decreased in skeletal muscle of pig fetuses exposed to maternal high-energy diets

Zou

et al. 2017

Animal

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“…Increases in mitochondrial biogenesis and function have previously been shown to improve insulin sensitivity (Bonnard et al., 2008; Joseph, Adhihetty, & Leeuwenburgh, 2016). Furthermore, caloric restriction (CR), which is currently the only nutritional intervention that delays aging and extends lifespan in mammals, is known to stimulate mitochondrial metabolism (Civitarese et al., 2007; Lopez‐Lluch et al., 2006).…”

Section: Resultsmentioning

confidence: 99%

“…Mitochondria are energy centers that produce ATP but are also the primary source of ROS, which reportedly induce cellular damage in skeletal muscle and precede the onset of insulin resistance (Bonnard et al., 2008). In the mitochondria, ROS are mainly produced by electron leakage from complexes I and III (Murphy, 2009).…”

Section: Resultsmentioning

confidence: 99%

“…In the present study, aged Nmnat3 Tg mice maintained ATP production and generated less ROS than their aged WT counterparts. Excessive intracellular ROS in skeletal muscles reportedly induces cellular damage and precedes the onset of insulin resistance (Bonnard et al., 2008). Therefore, reduced ROS levels would likely be protective against diet‐induced and aging‐associated insulin resistance in Nmnat3 Tg mice.…”

Section: Discussionmentioning

confidence: 99%

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Overexpression of Nmnat3 efficiently increases NAD and NGD levels and ameliorates age‐associated insulin resistance

et al. 2018

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SummaryNicotinamide adenine dinucleotide (NAD) is an important cofactor that regulates various biological processes, including metabolism and gene expression. As a coenzyme, NAD controls mitochondrial respiration through enzymes of the tricarboxylic acid (TCA) cycle, β‐oxidation, and oxidative phosphorylation and also serves as a substrate for posttranslational protein modifications, such as deacetylation and ADP‐ribosylation by sirtuins and poly(ADP‐ribose) polymerase (PARP), respectively. Many studies have demonstrated that NAD levels decrease with aging and that these declines cause various aging‐associated diseases. In contrast, activation of NAD metabolism prevents declines in NAD levels during aging. In particular, dietary supplementation with NAD precursors has been associated with protection against age‐associated insulin resistance. However, it remains unclear which NAD synthesis pathway is important and/or efficient at increasing NAD levels in vivo. In this study, Nmnat3 overexpression in mice efficiently increased NAD levels in various tissues and prevented aging‐related declines in NAD levels. We also demonstrated that Nmnat3‐overexpressing (Nmnat3 Tg) mice were protected against diet‐induced and aging‐associated insulin resistance. Moreover, in skeletal muscles of Nmnat3 Tg mice, TCA cycle activity was significantly enhanced, and the energy source for oxidative phosphorylation was shifted toward fatty acid oxidation. Furthermore, reactive oxygen species (ROS) generation was significantly suppressed in aged Nmnat3 Tg mice. Interestingly, we also found that concentrations of the NAD analog nicotinamide guanine dinucleotide (NGD) were dramatically increased in Nmnat3 Tg mice. These results suggest that Nmnat3 overexpression improves metabolic health and that Nmnat3 is an attractive therapeutic target for metabolic disorders that are caused by aging.

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Combination of 5‐aminolevulinic acid and ferrous ion reduces plasma glucose and hemoglobin A1c levels in Zucker diabetic fatty rats

et al. 2016

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Mitochondrial dysfunction is associated with type 2 diabetes mellitus (T2 DM ). 5‐Aminolevulinic acid ( ALA ), a natural amino acid produced only in the mitochondria, is a precursor of heme. Cytochromes that contain heme play an important role in aerobic energy metabolism. Thus, ALA may help reduce T2 DM ‐associated hyperglycemia. In this study, we investigated the effect of ALA combined with sodium ferrous citrate ( SFC ) on hyperglycemia in Zucker diabetic fatty ( ZDF ) rats. We found that the gavage administration of ALA combined with SFC ( ALA / SFC ) for 6 weeks reduced plasma glucose and hemoglobin A1c (HbA1c) levels in rats without affecting plasma insulin levels. The glucose‐lowering effect depended on the amount of ALA / SFC administered per day. Furthermore, the glucose tolerance was also significantly improved by ALA / SFC administration. Although food intake was slightly reduced in the rats administered ALA / SFC , there was no effect on their body weight. Importantly, ALA / SFC administration induced heme oxygenase‐1 ( HO ‐1) expression in white adipose tissue and liver, and the induced expression levels of HO ‐1 correlated with the glucose‐lowering effects of ALA / SFC . Taken together, these results suggest that ALA combined with ferrous ion is effective in reducing hyperglycemia of T2 DM without affecting plasma insulin levels. HO ‐1 induction may be involved in the mechanisms underlying the glucose‐lowering effect of ALA / SFC .

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Mitochondrial dysfunction results from oxidative stress in the skeletal muscle of diet-induced insulin-resistant mice

Cited by 534 publications

References 37 publications

Mitochondrial biogenesis is decreased in skeletal muscle of pig fetuses exposed to maternal high-energy diets

Mitochondrial biogenesis is decreased in skeletal muscle of pig fetuses exposed to maternal high-energy diets

Overexpression of Nmnat3 efficiently increases NAD and NGD levels and ameliorates age‐associated insulin resistance

Combination of 5‐aminolevulinic acid and ferrous ion reduces plasma glucose and hemoglobin A1c levels in Zucker diabetic fatty rats

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