OBJECTIVE: Recent observations indicate that the delivery of nitric oxide by endothelial nitric oxide synthase (eNOS) is not only critical for metabolic homeostasis, but could also be important for mitochondrial biogenesis, a key organelle for free fatty acid (FFA) oxidation and energy production. Because mice deficient for the gene of eNOS (eNOS(-/-)) have increased triglycerides and FFA levels, in addition to hypertension and insulin resistance, we hypothesized that these knockout mice may have decreased energy expenditure and defective beta-oxidation. RESEARCH DESIGN AND METHODS: Several markers of mitochondrial activity were assessed in C57BL/6J wild-type or eNOS(-/-) mice including the energy expenditure and oxygen consumption by indirect calorimetry, in vitro beta-oxidation in isolated mitochondria from skeletal muscle, and expression of genes involved in fatty acid oxidation. RESULTS: eNOS(-/-) mice had markedly lower energy expenditure (-10%, P < 0.05) and oxygen consumption (-15%, P < 0.05) than control mice. This was associated with a roughly 30% decrease of the mitochondria content (P < 0.05) and, most importantly, with mitochondrial dysfunction, as evidenced by a markedly lower beta-oxidation of subsarcolemmal mitochondria in skeletal muscle (-30%, P < 0.05). Finally, impaired mitochondrial beta-oxidation was associated with a significant increase of the intramyocellular lipid content (30%, P < 0.05) in gastrocnemius muscle. CONCLUSIONS: These data indicate that elevated FFA and triglyceride in eNOS(-/-) mice result in defective mitochondrial beta-oxidation in muscle cells.
OBJECTIVE: Recent observations indicate that the delivery of nitric oxide by endothelial nitric oxide synthase (eNOS) is not only critical for metabolic homeostasis, but could also be important for mitochondrial biogenesis, a key organelle for free fatty acid (FFA) oxidation and energy production. Because mice deficient for the gene of eNOS (eNOS(-/-)) have increased triglycerides and FFA levels, in addition to hypertension and insulin resistance, we hypothesized that these knockout mice may have decreased energy expenditure and defective beta-oxidation. RESEARCH DESIGN AND METHODS: Several markers of mitochondrial activity were assessed in C57BL/6J wild-type or eNOS(-/-) mice including the energy expenditure and oxygen consumption by indirect calorimetry, in vitro beta-oxidation in isolated mitochondria from skeletal muscle, and expression of genes involved in fatty acid oxidation. RESULTS:eNOS(-/-) mice had markedly lower energy expenditure (-10%, P < 0.05) and oxygen consumption (-15%, P < 0.05) than control mice. This was associated with a roughly 30% decrease of the mitochondria content (P < 0.05) and, most importantly, with mitochondrial dysfunction, as evidenced by a markedly lower beta-oxidation of subsarcolemmal mitochondria in skeletal muscle (-30%, P < 0.05). Finally, impaired mitochondrial beta-oxidation was associated with a significant increase of the intramyocellular lipid content (30%, P < 0.05) in gastrocnemius muscle. CONCLUSIONS: These data indicate that elevated FFA and triglyceride in eNOS(-/-) mice result in defective mitochondrial beta-oxidation in muscle cells.
Authors: Margarita Tenopoulou; Paschalis-Thomas Doulias; Kent Nakamoto; Kiara Berrios; Gabriella Zura; Chenxi Li; Michael Faust; Veronika Yakovishina; Perry Evans; Lu Tan; Michael J Bennett; Nathaniel W Snyder; William J Quinn; Joseph A Baur; Dmitriy N Atochin; Paul L Huang; Harry Ischiropoulos Journal: JCI Insight Date: 2018-08-23
Authors: Heather B Eccleston; Kelly K Andringa; Angela M Betancourt; Adrienne L King; Sudheer K Mantena; Telisha M Swain; Heather N Tinsley; Ryan N Nolte; Tim R Nagy; Gary A Abrams; Shannon M Bailey Journal: Antioxid Redox Signal Date: 2011-03-31 Impact factor: 8.401