FFA-Induced Hypertension and Endothelial Dysfunction
Condition: Endothelial Dysfunction; Hypertension
MeSH terms: Hypertension
Study type: Interventional

Summary: 
      The study is a prospective open label study to examine the effects of oral and intravenous
      fat load on blood pressure, endothelial function, sympathetic activity, and oxidative stress
      in obese healthy subjects. Subjects will receive either 8-hour of intravenous or oral fat
      loads in either low or high doses or normal saline in random order. Blood samples are drawn
      and vitals are measured before and after the infusions. Endothelial function and plasma
      glucose and lipid levels are measured to study the effects.
    

Detailed description: 
      Insulin resistance has been implicated as the central mechanism in the development of several
      cardiovascular risk factors including hypertension, diabetes, lipid disorders, and
      coagulation disorders. Recent evidence suggests that increased levels of a circulation fat
      (free fatty acids or FFAs) are a leading candidate causing insulin resistance. Our
      preliminary studies in indicate that, in addition to insulin resistance, the infusion of
      Intralipid and heparin to increase FFAs resulted in a significant rise in systolic and
      diastolic blood pressure, impaired endothelial (vascular) function, and increased
      inflammatory markers in obese African Americans with and without diabetes. The effects of FFA
      on insulin action are well established; however, the blood pressure and vascular effects of
      FFAs infusion in obese subjects have not been fully investigated. We hypothesize that
      observed changes in blood pressure are the result of acute endothelial dysfunction, and/or
      increased activation of the autonomic nervous system. No previous studies have attempted to
      determine a dose response effect of increasing FFA on blood pressure. In addition, it is not
      know if increased FFAs by repeated oral fat load results in similar blood pressure than
      intravenous lipid infusion. Accordingly, we propose: 1) a systematic evaluation of the
      effects of increasing FFA levels on blood pressure and endothelial (vascular) function, and
      2) determine the effects of comparable increases in FFA concentration via intravenous
      infusion of Intralipid or by repeated oral fat load on blood pressure, insulin resistance and
      endothelial dysfunction in obese subjects.

      A group of obese normotensive subjects will be admitted to the Grady Clinical Research Center
      or to the Outpatient Research Unit in the Grady Diabetes Clinic on five occasions. In four of
      these admissions, research subjects will receive an 8-hour intravenous infusion, in random
      order, of increasing Intralipid concentration (10 ml, 20 ml, 40 ml per hour) or normal saline
      (40 ml per hour). During the final admission, research subjects will receive an oral liquid
      fat diet every 2 hours for 8-hours. The effect of increased FFAs on blood pressure and
      endothelial (vascular) function via intravenous infusion and via oral fat load therapy will
      be assessed.
    

Intervention name(s): Intralipid 20% @ 20cc/hour; Intralipid 20%@ 40cc/hour; Normal Saline; 32-gram oral fat load; 64-gram oral fat load
Intervention type(s): Drug; Drug; Drug; Dietary Supplement; Dietary Supplement
Intervention description(s): In this arm subjects received Intralipid 20% Intravenous IV continuous infusion at 20cc/hour for 8 hours. The 20% intralipid solution is a long-chain triglyceride emulsion composed of 50% polyunsaturated fatty acids, 26% monounsaturated fatty acids, and 19% saturated fatty acids. During the intralipid infusion studies, subjects remained fasting; In this arm subjects received Intralipid 20% IV continuous infusion at 40cc/hour for 8 hours. In this arm subjects will receive Intralipid 20% Intravenous IV continuous infusion at 20cc/hour for 8 hours. The 20% intralipid solution is a long-chain triglyceride emulsion composed of 50% polyunsaturated fatty acids, 26% monounsaturated fatty acids, and 19% saturated fatty acids. During the intralipid infusion studies, subjects remained fasting.; In this arm subjects received 0.9% Normal Saline continuous IV infusion at 40/cc for 8 hours.; In this arm subjects received oral liquid fat load prepared by the General Clinical Research Center (GCRC) at baseline and every 2 hours for 6 hours. Participants received fat with Free Fatty Acids (FFA) composed of 33% polyunsaturated fatty acids, 34% monounsaturated fatty acids, and 22% saturated fatty acids. The oral fat load in either low or high dose was given in four equally divided doses at 0, 2, 4, and 6 h.; In this arm subjects received 60-gram oral fat load intake at baseline and every 2 hours for 6 hours prepared by the General Clinical Research Center (GCRC). Participants received fat with Free Fatty Acids (FFA) composed of 33% polyunsaturated fatty acids, 34% monounsaturated fatty acids, and 22% saturated fatty acids. The oral fat load in either low or high dose was given in four equally divided doses at 0, 2, 4, and 6 h.
Other intervention name(s): 20% i.v. fat emulsion; 20% i.v. fat emulsion; 0.9% Sodium Chloride
Intervention MeSH terms: Soybean oil, phospholipid emulsion
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Primary purpose: Other
Keywords: hypertension; metabolic syndrome; vascular reactivity; Elevated blood pressure; lipid toxicity