Metabolic Heterogeneity Underlying Hypertriglyceridemia: Hepatic Triglyceride Biosynthesis in Humans With Different Insulin Resistance Phenotypes

The focus of this cross-sectional study is to determine the effects of tissue-specific (adipose tissue or muscle) vs global (combined) insulin resistance (IR) on hepatic triglyceride biosynthesis in humans, and to determine differential effects of an acute exercise intervention on hepatic triglyceride biosynthesis in these groups.

Inclusion Criteria:Ability to give informed consentOverweight, defined as BMI 25-30 kg/m2Modest hypertriglyceridemia, defined as fasting plasma triglycerides 1.5-3.0mMHigh risk of insulin resistance, defined as fasting plasma insulin >64pMStable weight for at least 3mo prior to participationExclusion Criteria:Active or chronic liver disease, kidney disease, congestive heart failure, unstable angina, history of acute cardiovascular events within 6mo of screening, history of seizures or syncope, or an active infection requiring antimicrobial therapy;Use of insulin, thiazolidinediones, SGLT2 inhibitors, or sulfonylureas;Use of fibrates, omega 3 (fish oil), niacin, or PCSK9 antagonists;Use of systemic glucocorticoids within 60d prior to participation;Hematocrit <35%;Pregnancy of breastfeeding;Active tobacco use, excessive alcohol intake (>14U/wk), or history of drug abuse.