NCT01520454

Effect of Increased Free Fatty Acids on Leptin Function

Differential Effects of Oral and Intravenous Lipid Administration on Leptin Signaling

• Status: Completed
• Phase: N/A
• Study type: Interventional
• Enrollment: 26 (actual)
• Sponsor: Beth Israel Deaconess Medical Center · Academic / Other
• Sex: All
• Age: 18 Years – 65 Years
• Healthy volunteers: Accepted

Summary

Obese people have elevated levels of the hormone leptin. Despite this, they seem to be resistant to the effects of this hormone, which usually regulates appetite and energy expenditure. This is similar to what happens with insulin levels in the obese. Furthermore, the way lipid ingestion versus lipid infusion may impact novel molecules secreted by tissues commonly affected in insulin resistant states such as liver and muscle have not yet been studied. The aim of the present study is to investigate the effect of oral vs. different doses of IV lipid administration on molecular parameters related to glucose and energy homeostasis using a randomized, placebo-controlled design. Additionally, we will examine how increased free fatty acids (FFAs) my impact intracellular leptin signaling such as the STAT3 pathway.

Detailed description

We propose to test our hypotheses by conducting a non-blinded, interventional study evaluating the effects of acute leptin administration on intracellular leptin signaling pathways after a 6 hour infusion period comparing an oral high fat meal, high fat lipid infusion, low fat lipid infusion, or placebo infusion (saline)iv lipid infusion, placebo (saline) and oral high fat meal. After a screening visit, study participation involves 1 meal pick-up visit, 1 overnight visit, and one 1 follow-up visit. Subjects will be randomized to one of 4 groups: an oral high fat meal, fat emulsion 20% infusion , fat emulsion 10% infusion, and a placebo (saline) infusion infusion and an oral high fat meal. We plan to screen 100 male and postmenopausal female subjects, with BMI greater than 18 kg/m2, to consent 60 in order to have 32-48 evaluable subjects, 8-12 subjects per group, completing all parts of the study. The primary study outcome to be evaluated will be the changes in serum concentrations of glucose, hormones influencing metabolism such as insulin, fat-cell-secreted proteins such as leptin, molecules involved in metabolism such as free fatty acids (FFAs), and markers of inflammation such as interleukin (IL)-2 and interferon (IFN)-gamma. The secondary outcome will be to examine the impacts of increased FFAs on intracellular leptin signaling by phosphorylation of STAT3.

Conditions

• Obesity
• Leptin Resistance

Interventions

Type	Name	Description
DRUG	Saline	IV saline at 0.83 mL/kg/hr for six hours
DRUG	Intralipid	Intralipid in either low-dose or high dose (10% vs. 20%) at 0.83 mL/kr/hr for six hours
DIETARY_SUPPLEMENT	Water	Water by mouth
DIETARY_SUPPLEMENT	oral fat	Soybean oil by mouth at 1.25 g/kg x 2 doses
DRUG	Heparin	Heparin bolus of 1000 units followed by 800 u/hr, adjust per partial thromboplastin time (PTT), for 5.5 hours

Timeline

• Start date: 2011-11-01
• Primary completion: 2013-12-01
• Completion: 2016-12-01
• First posted: 2012-01-30
• Last updated: 2018-05-11
• Results posted: 2017-04-26

Locations

1 site across 1 country: United States