Increasing mitochondrial muscle fatty acid oxidation induces skeletal muscle remodeling toward an oxidative phenotype

Hénique, Carole; Mansouri, Ali; Vávrová, Eliška; Lenoir, Véronique; Ferry, Arnaud; Esnous, Catherine; Ramond, Elodie; Girard, Jean; Bouillaud, Frédéric; Prip‐Buus, Carina; Cohen, Isabelle

doi:10.1096/fj.14-257717

Cited by 45 publications

(49 citation statements)

References 54 publications

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“…A similar observation has been made in a mouse model of Duchenne Muscular Dystrophy which overexpresses a gain-of-function version of SIRT1 specifically in the muscle from birth 36 and by administration of the activator SRT1720, 16 suggesting that SIRT1 overexpression or activation induces fiber remodeling toward an oxidative phenotype. Ppard , Sirt3 , and Cpt1b overexpression may also induce shift toward the oxidative fiber type, 5,37,38 and their up-regulation in AAV1- Sirt1 -treated mice may have contributed to the shift from type 2 to type 1 fibers and also to a more oxidative phenotype in gastrocnemius and quadriceps muscles of these mice.…”

Section: Discussionmentioning

confidence: 95%

AAV-mediated Sirt1 overexpression in skeletal muscle activates oxidative capacity but does not prevent insulin resistance

Vil

Roca

Elias

et al. 2016

Molecular Therapy - Methods & Clinical Development

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Type 2 diabetes is characterized by triglyceride accumulation and reduced lipid oxidation capacity in skeletal muscle. SIRT1 is a key protein in the regulation of lipid oxidation and its expression is reduced in the skeletal muscle of insulin resistant mice. In this tissue, Sirt1 up-regulates the expression of genes involved in oxidative metabolism and improves mitochondrial function mainly through PPARGC1 deacetylation. Here we examined whether Sirt1 overexpression mediated by adeno-associated viral vectors of serotype 1 (AAV1) specifically in skeletal muscle can counteract the development of insulin resistance induced by a high fat diet in mice. AAV1-Sirt1-treated mice showed up-regulated expression of key genes related to β-oxidation together with increased levels of phosphorylated AMP protein kinase. Moreover, SIRT1 overexpression in skeletal muscle also increased basal phosphorylated levels of AKT. However, AAV1-Sirt1 treatment was not enough to prevent high fat diet-induced obesity and insulin resistance. Although Sirt1 gene transfer to skeletal muscle induced changes at the muscular level related with lipid and glucose homeostasis, our data indicate that overexpression of SIRT1 in skeletal muscle is not enough to improve whole-body insulin resistance and that suggests that SIRT1 has to be increased in other metabolic tissues to prevent insulin resistance.

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Section: Discussionmentioning

confidence: 95%

AAV-mediated Sirt1 overexpression in skeletal muscle activates oxidative capacity but does not prevent insulin resistance

Vil

Roca

Elias

et al. 2016

Molecular Therapy - Methods & Clinical Development

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show abstract

“…The endocrine axis between muscle and bone, consisting of insulin-like growth factor 1, interleukins (ILs) 6, 7, and 15, and osteoglycin, and vice versa for sclerostin with its muscle counterparts myostatin and osteocalcin, is impaired in osteoporosis and, therefore, in sarcopenia—they seem to be “two sides of the same coin” [16–19]. Recent studies also showed a significant loss of number, thickness, and capillarization of muscle fibres with a majority of type II fibre loss [20–22]. …”

Section: Introductionmentioning

confidence: 99%

Effect of the Lipoxygenase Inhibitor Baicalein on Muscles in Ovariectomized Rats

Saul

Kling

Kosinsky

et al. 2016

Journal of Nutrition and Metabolism

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Sarcopenia, a loss of muscle mass accompanying osteoporosis, leads to falls and fall-related injuries. Baicalein, as a phytochemical agent, has an antioxidative and anti-inflammatory effect in muscle. In this study, sixty-one female Sprague Dawley rats were divided into five groups: four groups were ovariectomized (OVX) and one control group was nonovariectomized (NON-OVX). Eight weeks after ovariectomy, three disparate concentrations (1 mg/kg body weight (BW), 10 mg/kg BW, and 100 mg/kg BW) of baicalein were applied subcutaneously daily in three OVX groups. Mm. soleus, gastrocnemius, and longissimus were extracted; their diameter, area, relation to body, and muscle weights as well as number of capillaries per fibre were recorded. In Mm. soleus and gastrocnemius, the baicalein effect (increasing number of capillaries per fibre) was proportional to the dose applied. The fibre diameters and area under baicalein treatment were significantly greater compared to OVX and NON-OVX groups. In M. longissimus, we observed a shift to type IIa fibres. Serum creatine kinase levels were significantly lower in highest baicalein concentration group. We conclude that baicalein can stimulate angiogenesis, though not fibre type-specific, in skeletal muscle and reduce the estrogen-related loss of fibre diameter and area in the skeletal muscle in rats. Therefore, a protective effect of baicalein on muscle cells can be assumed.

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“…AMP-activated protein kinase (AMPK) is a sensor of energy status that regulates energy metabolism including lipid metabolism (Kohjima et al 2008). Acetyl-CoA is responsible for producing malonyl CoA, a carnitine palmitoyl transferase 1 (CPT1) inhibitor (Dobrzyn et al 2004, Hénique et al 2015. Our study showed that AMPK mRNA and P-AMPK protein levels in the 4-VCD + HFD group decreased significantly compared with the Control group.…”

Section: Discussionmentioning

confidence: 69%

Danzhi Qing'e (DZQE) activates AMPK pathway and regulates lipid metabolism in a rat model of perimenopausal hyperlipidaemia

Asare

Wang

et al. 2016

Experimental Physiology

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What is the central question of this study? Does Danzhi Qing'e (DZQE) regulate lipid metabolism and improve ovarian function in a rat model of perimenopausal hyperlipidaemia, and could this effect be mediated through the AMPK pathway? What is the main finding and its importance? We revealed that DZQE is a pharmacotherapy that could activate the AMPK pathway to improve ovarian function and lipid metabolism during perimenopause complicated with hyperlipidaemia syndrome in an animal model. Thus, this study provides a novel therapeutic option for treating perimenopausal syndrome and highlights the therapeutic potential of DZQE in perimenopausal rats. Menopause is an important event in a woman's life. During perimenopause, accompanied by development of osteoporosis and dyslipidaemia, ovarian function gradually declines. Dyslipidaemia is a risk factor for cardiovascular disorders, cerebrovascular disease and breast cancer in postmenopausal women. All of these contribute to impairment of liver function, particularly fatty liver disease, because liver dysfunction is associated with ovarian dysfunction and hyperlipidaemia. The aim of this study was to define a therapeutic approach to improve ovarian function and attenuate lipid accumulation in order to prevent perimenopause-induced ovarian dysfunction and hyperlipidaemia. Four-week-old female Wistar rats were injected i.p. with 4-vinylcyclohexene diepoxide (4-VCD) and fed with a high-fat diet (HFD) to serve as a model of perimenopause complicated with hyperlipidaemia. The 4-VCD induces perimenopause, while the HFD causes hyperlipidaemia. Five days after administration of 4-VCD, the 4-VCD + HFD-treated rats were assessed daily for oestrous cycle stage by vaginal cytology. Rats were then assigned into groups, in which 2.5, 5.0 or 10.0 g kg Danzhi Qing'e (DZQE) or estradiol valerate was administered intragastrically for 8 weeks. Expression levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), oestrogen and testosterone measured by enzyme-linked immunosorbent assay served as biomarkers for perimenopause and ovarian dysfunction. The expression levels of AMPK and acetyl-CoA carboxylase in the liver were determined with Western blotting, and aspartate aminotransferase and alanine aminotransferase were analysed using an automated biochemical analyser to examine liver function. The DZQE improved ovarian function by upregulating oestrogen and testosterone concentrations in serum and downregulating FSH and LH serum concentrations. Moreover, DZQE reduced serum concentrations of triglyceride, total cholesterol and low-density lipoprotein in a dose-dependent manner to regulate lipid levels during perimenopause. Furthermore, DZQE increased AMPK at both the transcriptional and translational levels and decreased the expression of SREBP-1c gene as well as its downstream target gene, fatty acid synthase. Danzhi Qing'e improved dyslipidaemia during menopause and also had an effect on liver function. Danzhi Qing'e is an effective Chinese herbal compound, which improves ovari...

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Increasing mitochondrial muscle fatty acid oxidation induces skeletal muscle remodeling toward an oxidative phenotype

Cited by 45 publications

References 54 publications

AAV-mediated Sirt1 overexpression in skeletal muscle activates oxidative capacity but does not prevent insulin resistance

AAV-mediated Sirt1 overexpression in skeletal muscle activates oxidative capacity but does not prevent insulin resistance

Effect of the Lipoxygenase Inhibitor Baicalein on Muscles in Ovariectomized Rats

Danzhi Qing'e (DZQE) activates AMPK pathway and regulates lipid metabolism in a rat model of perimenopausal hyperlipidaemia

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