Mitochondrial Respiratory Capacity and Content Are Normal in Young Insulin-Resistant Obese Humans

Considerable debate exists about whether alterations in mitochondrial respiratory capacity and/or content play a causal role in the development of insulin resistance during obesity. The current study was undertaken to determine whether such alterations are present during the initial stages of insulin resistance in humans. Young (∼23 years) insulin-sensitive lean and insulin-resistant obese men and women were studied. Insulin resistance was confirmed through an intravenous glucose tolerance test. Measures of mitochondrial respiratory capacity and content as well as H(2)O(2) emitting potential and the cellular redox environment were performed in permeabilized myofibers and primary myotubes prepared from vastus lateralis muscle biopsy specimens. No differences in mitochondrial respiratory function or content were observed between lean and obese subjects, despite elevations in H(2)O(2) emission rates and reductions in cellular glutathione. These findings were apparent in permeabilized myofibers as well as in primary myotubes. The results suggest that reductions in mitochondrial respiratory capacity and content are not required for the initial manifestation of peripheral insulin resistance

Mast cells contribute to altered vascular reactivity and ischemia-reperfusion injury following cerium oxide nanoparticle instillation. Nanotoxicology

Abstract Cerium oxide (CeO 2 ) represents an important nanomaterial with wide ranging applications. However, little is known regarding how CeO 2 exposure may influence pulmonary or systemic inflammation. Furthermore, how mast cells would influence inflammatory responses to a nanoparticle exposure is unknown. We thus compared pulmonary and cardiovascular responses between C57BL/6 and B6.Cg-Kit W-sh mast cell deficient mice following CeO 2 nanoparticle instillation. C57BL/6 mice instilled with CeO 2 exhibited mild pulmonary inflammation. However, B6.Cg-Kit W-sh mice did not display a similar degree of inflammation following CeO 2 instillation. Moreover, C57BL/6 mice instilled with CeO 2 exhibited altered aortic vascular responses to adenosine and an increase in myocardial ischemia/reperfusion injury which was absent in B6.Cg-Kit W-sh mice. In vitro CeO 2 exposure resulted in increased production of PGD 2 , TNF-a, IL-6 and osteopontin by cultured mast cells. These findings demonstrate that CeO 2 nanoparticles activate mast cells contributing to pulmonary inflammation, impairment of vascular relaxation and exacerbation of myocardial ischemia/reperfusion injury