Effect of Increased Free Fatty Acids on Leptin Function

NCT01520454 | Completed Results

• 1 other identifier: 2009P000370
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Obesity; Leptin Resistance

Keywords

Leptin resistance; Free fatty acids; Lipotoxicity

Outcome Measures

Primary Outcomes (4)

• Change in Circulating Glucagon-like Peptide-1 (GLP-1) Levels

  The GLP-1 area under the curve (AUC) was calculated from baseline to six hours

  Baseline to 6 hours

• Change in Circulating Gastric Inhibitory Polypeptide (GIP) Levels

  The GIP AUC fwas calculated from baseline to six hours

  Baseline to 6 hours

• Change in Circulating Ghrelin Levels

  The Ghrelin AUC was calculated from baseline to six hours

  Baseline to 6 hours

• Change in Circulating Peptide Tyrosine Tyrosine (PYY) Levels

  The PYY AUC was calculated from baseline to six hours

  Baseline to 6 hours

Secondary Outcomes (5)

• Change in Circulating Glucose Levels

  Baseline to 6 hours

• Change in Circulating Insulin Levels

  Baseline to 6 hours

• Change in Circulating Leptin Levels

  Baseline to 6 hours

• Change in Circulating Adiponectin Levels

  Baseline to 6 hours

• Phosphorylation of STAT3 Pathways Downstream of Leptin After Lipid Administration

  Baseline to 6 hours

Study Arms (4)

Placebo

PLACEBO COMPARATOR

IV saline with heparin, oral water

Drug: Saline; Dietary Supplement: Water; Drug: Heparin

High dose fat solution

EXPERIMENTAL

Intralipid at high dose, with heparin and PO water

Drug: Intralipid; Dietary Supplement: Water; Drug: Heparin

Low dose fat solution

EXPERIMENTAL

Low dose IV Intralipid with heparin and PO water

Drug: Intralipid; Dietary Supplement: Water; Drug: Heparin

Oral fat

EXPERIMENTAL

Oral fat load with IV saline

Drug: Saline; Dietary Supplement: Water; Dietary Supplement: oral fat

Interventions

Saline DRUG

IV saline at 0.83 mL/kg/hr for six hours

Oral fat; Placebo

Intralipid DRUG

Intralipid in either low-dose or high dose (10% vs. 20%) at 0.83 mL/kr/hr for six hours

Also known as: intravenous lipids

High dose fat solution; Low dose fat solution

Water DIETARY_SUPPLEMENT

Water by mouth

High dose fat solution; Low dose fat solution; Oral fat; Placebo

oral fat DIETARY_SUPPLEMENT

Soybean oil by mouth at 1.25 g/kg x 2 doses

Also known as: soybean oil

Oral fat

Heparin DRUG

Heparin bolus of 1000 units followed by 800 u/hr, adjust per partial thromboplastin time (PTT), for 5.5 hours

Also known as: anti coated

High dose fat solution; Low dose fat solution; Placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18-65

You may not qualify if:

• Subjects with a history of any illness, other than obesity, that may affect insulin sensitivity (anemia, infectious diseases, renal or hepatic failure, uncontrolled hypertension, cancer, lymphoma, chronic inflammatory conditions such as inflammatory bowel disease and rheumatoid arthritis, states of cortisol or growth hormone excess, alcoholism or drug abuse, and eating disorders).
• History of diabetes mellitus.
• Subjects taking any medications that are known to influence glucose metabolism such as glucocorticoids will also be excluded. We will screen for these conditions by means of a detailed history and review of systems and physical examination (see below).
• Subjects taking any medications known to affect lipids such as statins will also be excluded. We will screen for these similar to above.
• Cholesterol greater or equal to 250 mg/dL and/or triglyceride levels greater than 500 mg/dL at the time of screening, as determined by laboratory testing.
• Subjects who have a known history of anaphylaxis or anaphylactoid-like reactions or who have a known hypersensitivity to anesthetic agents such as Lidocaine or Marcaine will be excluded from the study.
• Hypersensitivity to fat emulsion or any component of the formulation; severe egg or legume (soybean) allergies; pathologic hyperlipidemia, lipoid nephrosis, acute pancreatitis associated with hyperlipemia.
• Hypersensitivity to heparin or any component of the formulation
• Severe thrombocytopenia, uncontrolled active bleeding, disseminated intravascular coagulation (DIC); suspected intracranial hemorrhage.
• Subjects with a history of bleeding dyscrasia, poor wound healing or any medical condition precluding supine position will be excluded from the study.
• Unable to follow study protocol or any condition that in the opinion of the investigator makes the subject unsuitable for the study.
• Pregnancy
• Prior history of gastrectomy, gastric bypass surgery, or other weight loss surgery.

Sponsors & Collaborators

• Beth Israel Deaconess Medical Center: lead

Study Sites (1)

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

Related Publications (1)

• Perakakis N, Kokkinos A, Angelidi AM, Tsilingiris D, Gavrieli A, Yannakoulia M, Tentolouris N, Mantzoros CS. Circulating levels of five proglucagon-derived peptides in response to intravenous or oral glucose or lipids and to a mixed-meal in subjects with normal weight, overweight, and obesity. Clin Nutr. 2022 Sep;41(9):1969-1976. doi: 10.1016/j.clnu.2022.07.001. Epub 2022 Jul 19.

  PMID: 35961260 DERIVED

Related Links

• Mantzoros Lab Home Page

MeSH Terms

Conditions

Obesity

Interventions

Sodium Chloride; soybean oil, phospholipid emulsion; Water; CD36 Antigens; Soybean Oil; Heparin

Condition Hierarchy (Ancestors)

Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds; Hydroxides; Alkalies; Anions; Ions; Electrolytes; Oxides; Oxygen Compounds; Platelet Membrane Glycoproteins; Membrane Glycoproteins; Glycoproteins; Glycoconjugates; Carbohydrates; Fatty Acid Transport Proteins; Membrane Transport Proteins; Carrier Proteins; Proteins; Amino Acids, Peptides, and Proteins; Membrane Proteins; Receptors, Cell Surface; Receptors, Immunologic; Scavenger Receptors, Class B; Receptors, Scavenger; Receptors, LDL; Receptors, Lipoprotein; Dietary Fats, Unsaturated; Dietary Fats; Fats; Lipids; Fats, Unsaturated; Plant Oils; Oils; Plant Preparations; Biological Products; Complex Mixtures; Food; Diet, Food, and Nutrition; Physiological Phenomena; Food and Beverages; Glycosaminoglycans; Polysaccharides

Results Point of Contact

• Title: Dr. Christos Manztoros
• Organization: Beth Israel Deaconess Medical Center

cmantzor@bidmc.harvard.edu

617-667-8630

Study Officials

• Christos S Mantzoros, MD, DSc

  Beth Israel Deaconess Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Medicine

Study Record Dates

• First Submitted: January 4, 2012
• First Posted: January 30, 2012
• Study Start: November 1, 2011
• Primary Completion: December 1, 2013
• Study Completion: December 1, 2016
• Last Updated: May 11, 2018
• Results First Posted: April 26, 2017

Record last verified: 2018-05

Locations

US (1)