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Biochim Biophys Acta. 2015 Jul;1852(7):1257-67. doi: 10.1016/j.bbadis.2015.03.005. Epub 2015 Mar 14.

Metformin and caloric restriction induce an AMPK-dependent restoration of mitochondrial dysfunction in fibroblasts from Fibromyalgia patients.

Author information

1
Research Laboratory, Oral Medicine Department, Universidad de Sevilla, Sevilla, Spain; Centro Andaluz de Biología del Desarrollo (CABD), Universidad Pablo de Olavide-CSIC-Junta de Andalucía and Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), ISCIII, 41013 Sevilla, Spain.
2
Centro Andaluz de Biología del Desarrollo (CABD), Universidad Pablo de Olavide-CSIC-Junta de Andalucía and Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), ISCIII, 41013 Sevilla, Spain.
3
Research Laboratory, Oral Medicine Department, Universidad de Sevilla, Sevilla, Spain; Dept. of Periodontology, Dental School, University of Sevilla, Spain.
4
Research Laboratory, Oral Medicine Department, Universidad de Sevilla, Sevilla, Spain.
5
División de Neurociencias, Universidad Pablo de Olavide de Sevilla, Carretera de Utrera Km. 1, 41013 Sevilla, Spain.
6
Dipartimento di Scienze Cliniche Specialistiche ed Odontostomatologiche (DISCO)-Sez. Biochimica, Facoltà di Medicina, Università Politecnica delle Marche, Ancona 60131, Italy; Area de Nutrición y Salud, Universidad Internacional Iberoamericana (UNINI), Campeche C.P.24040, Mexico; Facultad de Ciencias de la Salud, Universidad Nacional de Chimborazo, Riobamba, Ecuador.
7
Dipartimento di Scienze Agrarie, Alimentari e Ambientali (D3A), Università Politecnica delle Marche, Via Ranieri 65, Ancona 60131, Italy.
8
Dipartimento di Scienze Cliniche Specialistiche ed Odontostomatologiche (DISCO)-Sez. Biochimica, Facoltà di Medicina, Università Politecnica delle Marche, Ancona 60131, Italy; Director Centre for Nutrition & Health, Universidad Europea del Atlantico (UEA), Santander 39011, Spain.
9
Research Laboratory, Oral Medicine Department, Universidad de Sevilla, Sevilla, Spain. Electronic address: mdcormor@us.es.

Abstract

Impaired AMPK is associated with a wide spectrum of clinical and pathological conditions, ranging from obesity, altered responses to exercise or metabolic syndrome, to inflammation, disturbed mitochondrial biogenesis and defective response to energy stress. Fibromyalgia (FM) is a world-wide diffused musculoskeletal chronic pain condition that affects up to 5% of the general population and comprises all the above mentioned pathophysiological states. Here, we tested the involvement of AMPK activation in fibroblasts derived from FM patients. AMPK was not phosphorylated in fibroblasts from FM patients and was associated with decreased mitochondrial biogenesis, reduced oxygen consumption, decreased antioxidant enzymes expression levels and mitochondrial dysfunction. However, mtDNA sequencing analysis did not show any important alterations which could justify the mitochondrial defects. AMPK activation in FM fibroblast was impaired in response to moderate oxidative stress. In contrast, AMPK activation by metformin or incubation with serum from caloric restricted mice improved the response to moderate oxidative stress and mitochondrial metabolism in FM fibroblasts. These results suggest that AMPK plays an essential role in FM pathophysiology and could represent the basis for a valuable new therapeutic target/strategy. Furthermore, both metformin and caloric restriction could be an interesting therapeutic approach in FM.

KEYWORDS:

AMPK; Caloric restriction; Fibromyalgia; Metformin; Mitochondria; Oxidative stress

PMID:
25779083
DOI:
10.1016/j.bbadis.2015.03.005
[Indexed for MEDLINE]
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