Effect of Fatty Liver on TCA Cycle Flux and the Pentose Phosphate Pathway

The investigators plan to determine whether nutritional state and fatty liver influence the production of [13C]bicarbonate from [1-13C]pyruvate via flux through the pyruvate dehydrogenase (PDH) reaction in healthy subjects compared to those with fatty liver. The long-term purpose of this work is to develop hyperpolarized 13C imaging as a method to directly assess metabolic pathways in the human liver. Many high-impact diseases such as insulin resistant states, fatty liver and inborn errors of metabolism are known to alter biochemical fluxes and for this reason it is important to detect altered activity in specific pathways.

Inclusion criteria

• Ages 18 to 99 years.
• All races, ethnicities and gender identification may be included. Subjects must meet all of the inclusion and exclusion criteria to be included in the study.
• Either fatty liver diagnosis (defined as >5.6% fat content in the liver) or healthy control
• While all races and ethnicities will be included, subjects must be able to read and speak the English language. Once the protocol is established, Spanish-speaking participants will be included.
• Women of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.

Exclusion criteria

Fatty Liver Subjects

• No subjects taking hypoglycemic agents or insulin will be enrolled. There is no exclusion based on fasting glucose.
• Subjects with major mental health conditions such as schizophrenia and bipolar disorder that would limit compliance with study requirements will not participate. In general, subjects with any form of medical instability such as seizure disorders, significant COPD, significant asthma, left ventricular dysfunction will not participate.
• Medications for control of hypercholesterolemia, hypertriglyceridemia or hyperglycemia.

Healthy Control Subjects

• Liver disease or other chronic illness
• Diagnosis of type I or type II diabetes
• No subjects taking hypoglycemic agents or insulin will be enrolled. There is no exclusion based on fasting glucose.
• A potential subject with any major medical, surgical or psychiatric condition will not participate. These conditions include but are not limited to thyroid disease, chronic metabolic illness, known vascular disease, current cancer diagnosis and/or treatment.
• Subjects with major mental health conditions such as schizophrenia and bipolar disorder that would limit compliance with study requirements will not participate. In general, subjects with any form of medical instability such as seizure disorders, significant COPD, significant asthma, left ventricular dysfunction will not participate.
• Medications for control of hypercholesterolemia, hypertriglyceridemia or hyperglycemia.

All Subjects

• No prior hepato-biliary surgery.
• Donated blood within the prior 4 weeks.
• Consume more than 10 grams of ethanol per day.
• Cirrhosis or any form of viral hepatitis.
• Prior documented hepatic reaction to drugs with a known hepatotoxicity profile such as isoniazid, methotrexate, phenytoin, propylthiouracil, valproate, etc.
• Pregnant/Lactating
• Receiving any other investigational agents.
• Any contraindication noted on the UTSWMC MRI Screening Form including implants contraindicated at 3T, pacemakers, Implantable Cardioverter Defibrillators (ICD), etc., and significant claustrophobia.