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.
Ability to give informed consent
Overweight, defined as BMI 25-30 kg/m2
Modest hypertriglyceridemia, defined as fasting plasma triglycerides 1.5-3.0mM
High risk of insulin resistance, defined as fasting plasma insulin >64pM
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;
Crossover
Standardized Dinner
BehavioralDe novo lipogenesis (DNL) will be assessed in all participants with a standardized dinner
Premeal exercise
BehavioralDNL will be assessed in all participants with short bouts of premeal exercise with a standardized dinner
Effect of tissue-specific insulin resistance on contribution of DNL to plasma triglyceride
The amount of de novo lipogenesis (DNL) in VLDL-triglycerides after a standard meal will be measured in plasma from whole blood. Relationship between DNL and 1) whole body (skeletal muscle) insulin resistance and 2) white adipose tissue insulin resistance will be assessed individually.
Change in DNL in VLDL-triglycerides after a standard meal compared to a standard meal with premeal exercise.
The amount of de novo lipogenesis (DNL) in VLDL-triglycerides after a standard meal vs after a standard meal with premeal exercise will be measured in plasma from whole blood.
Change in plasma triglycerides after a standard meal compared to a standard meal with premeal exercise
Plasma triglycerides will be measured under both conditions.
Baseline plasma triglycerides
Plasma triglycerides will be measured at the screening visit to determine eligibility for the study
Adipose insulin sensitivity
Both nonesterified fatty acids and insulin will be measured in the plasma at baseline to calculate Adipo-IR, a measure of adipose tissue insulin sensitivity.
Skeletal muscle/whole-body insulin sensitivity assessed by oral glucose tolerance test (OGTT)
Matsuda index will be used to evaluate whole body physiological insulin sensitivity from the data obtained by OGTT. Insulin sensitivity as calculated by the Matsuda index: \[10,000 / √glucose minute 0 x insulin minute 0) (mean glucose (OGTT) x mean insulin OGTT)\]. A higher result indicates less IR.
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Yale University
Lead sponsor
Amsterdam UMC
Collaborator
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Collaborator
