Muscle OXPHOS and Nutrient Homeostasis

Exclusion Criteria

• •For all study groups (i.e., mitochondrial disease, normal weight, obese):
• •1. Diabetes (HgbA1c \> 6.4%) and/or taking insulin or other anti-diabetic drug therapy within the 4 weeks prior to enrollment.
• •2. Use of any lipid-lowering medication (excluding nutritional supplements) within the 4 weeks prior to enrollment.
• •3. Any contraindication to MRI study (e.g., implanted non-compatible device, pacemaker, known claustrophobia).
• •4. Kidney disease. Estimated glomerular filtration rate \< 60 ml/min/1.73 m2 (calculated using the subject's measure serum creatinine and the Modification of Diet in Renal Disease \[MDRD\] study estimation formula).
• •5. Liver disease. Persistent elevation of liver function tests at the time of study entry. Persistent SGOT (AST), SGPT (ALT), Alk Phos or total bilirubin, with values \> 3 times normal upper limits, will exclude a subject from study participation.
• •6. Severe co-existing cardiac disease, characterized by any one of these self-reported conditions:
• •1. recent myocardial infarction (within the past 6 months).
• •2. evidence of ischemia on functional cardiac exam within the last year
• •3. left ventricular ejection fraction \< 30%.
• •7. Acute or chronic pancreatitis.
• •8. Receiving treatment for a medical condition requiring chronic use of systemic (oral or parenteral steroids, except for the use of \< 5 mg prednisone daily, or an equivalent dose of hydrocortisone, for physiological replacement only.
• •9. Anemia (baseline hemoglobin concentration \< 11 g/dl in women and \<12 g/dl in men), lymphopenia, (\< 1,000/µL), neutropenia (\< 1,500/µL), or thrombocytopenia (platelets \< 100,000/µL).
• •10. Any known coagulopathy (including Factor V deficiency) or medical condition requiring long-term anticoagulant therapy (e.g., warfarin) (low-dose aspirin treatment is allowed) or patients with an INR \> 1.5.
• •11. For female participants: Positive pregnancy test.
• •12. Known active alcohol or substance abuse, including known tobacco use.
• •13. Use of any investigational agents within 4 weeks of enrollment.
• •14. Inability to fast comfortably for 10 hours (i.e., overnight).
• •15. Individuals who have a pacemaker, metal implants, claustrophobia, have worked around a metal grinder or a construction site, or that have known medical conditions which can be exacerbated by stress such as anxiety or panic attacks. Inability to lie flat in the MRI scanner for 90 minutes is also an exclusion criterion.
• •* ANY intra-luminal implant, filter, stent or valve replacement
• •* ANY type of life assist device, pump, or prosthetic
• •* ANY vascular clip or clamp
• •* ANY surgically placed clips or clamps or bands on visceral organs
• •* ANY intracranial implants of any type other than dental fillings
• •* ANY non-removable piercings, jewelry, or medicinal patch
• •* ANY personal history of intraocular injury or fragment in or around the orbit that cannot be cleared through radiologic examination.
• •* ANY personal history of bullet, shrapnel, or stabbing wounds that cannot be cleared through radiologic evaluation.
• •16. Any medical condition that, in the opinion of the investigator, will interfere with the safe completion of the study.