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The Effect of Succinate on Skeletal Muscle Respiration in Diet Induced Obesity and Insulin Resistance
Author(s) -
Slocum Cheyanne,
Escudero Daniela,
Sheridan Caitlin,
Legesse Saada,
Lagalwar Sarita,
Reynolds Thomas,
Ives Stephen
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.1036.5
Subject(s) - medicine , endocrinology , insulin resistance , skeletal muscle , mitochondrial biogenesis , mitochondrion , insulin , adipose tissue , respiration , energy homeostasis , biology , chemistry , obesity , biochemistry , anatomy
Obesity and insulin resistance are associated with mitochondrial dysfunction. We sought to determine the effect of succinate, an electron donor at complex II of the mitochondria, on insulin action, energy homeostasis, and muscle mitochondrial function. C57B6 male mice were randomly assigned to a low fat diet (LFD) or a high fat diet (HFD) for 20 weeks. After 14 weeks of the dietary intervention, mice from within a diet group were assigned to a control or succinate (0.75 mg/ml in drinking water) group. Caloric intake, water consumption, and body mass were assessed weekly, while glucose tolerance (GT), insulin tolerance (IT), energy expenditure (EE), and spontaneous physical activity (PA) were assessed during the last 2 weeks of succinate treatment. In vitro measurements of mitochondrial function in soleus muscle were performed using permeabilized fiber respirometry. As expected, the HFD increased body mass, epididymal white adipose tissue (EWAT) mass, and reduced GT and IT. However, succinate treatment had no effect on any in vivo measurements (body mass, EWAT mass, GT, IT, EE, or PA). Despite impaired insulin action, there was no effect of diet on soleus muscle mitochondrial respiration, however, a trend to increase complex I+II driven state 3 respiration, and complex IV activity was evident in mice that received succinate. In conclusion, we observed no effect of succinate treatment on insulin action, energy homeostasis, or physical activity. In oxidative skeletal muscle, there was a tendency for increased state 3 respiration, owed to greater mitochondrial content, suggestive of a succinate‐induced mitochondrial biogenesis.