The Spanish group is at it again! Their latest study indicated that the mitochondria from very interesting type of cell called a fibroblast which produces connective tissue - a major issue in FM - are pretty tweaked. An important enzyme in mitochondrial actiivty - AMPK - was not activated.
"AMP-activated protein kinase (AMPK) is a crucial cellular energy sensor. Once activated by falling energy status, it promotes ATP production"
Mitochondrial production, antioxidant levels and oxygen consumption were down in these crucial cells that keep the connective tissue healthy. Is this why myofascial problems are so common in FM?
Interestingly metformin -a diabetic drug - and caloric restriction - helped, it appears, to increase AMPK production.
Biochim Biophys Acta. 2015 Mar 13. pii: S0925-4439(15)00069-1. doi: 10.1016/j.bbadis.2015.03.005. [Epub ahead of print] Metformin and caloric restriction induce an AMPK-dependent restoration of mitochondrial dysfunction in fibroblasts from Fibromyalgia patients.
Alcocer-Gómez E1, Garrido-Maraver J2, Bullón P3, Marín-Aguilar F4, Cotán D2, Carrión AM5, Alvarez-Suarez JM6, Giampieri F7, Sánchez-Alcazar JA2, Battino M8, Cordero MD9.
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 or caloric restriction could be an interesting therapeutic approach in FM.
"AMP-activated protein kinase (AMPK) is a crucial cellular energy sensor. Once activated by falling energy status, it promotes ATP production"
Mitochondrial production, antioxidant levels and oxygen consumption were down in these crucial cells that keep the connective tissue healthy. Is this why myofascial problems are so common in FM?
Interestingly metformin -a diabetic drug - and caloric restriction - helped, it appears, to increase AMPK production.
Biochim Biophys Acta. 2015 Mar 13. pii: S0925-4439(15)00069-1. doi: 10.1016/j.bbadis.2015.03.005. [Epub ahead of print] Metformin and caloric restriction induce an AMPK-dependent restoration of mitochondrial dysfunction in fibroblasts from Fibromyalgia patients.
Alcocer-Gómez E1, Garrido-Maraver J2, Bullón P3, Marín-Aguilar F4, Cotán D2, Carrión AM5, Alvarez-Suarez JM6, Giampieri F7, Sánchez-Alcazar JA2, Battino M8, Cordero MD9.
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 or caloric restriction could be an interesting therapeutic approach in FM.
![ME/CFS lecture | Dr Nancy Klimas | 2011 [Chronic Fatigue Syndrome / SEID / New Zealand] - YouTube](data:image/gif;base64,R0lGODlhAQABAIAAAAAAAP///yH5BAEAAAAALAAAAAABAAEAAAIBRAA7)
