Adipose Tissue Response to Overfeeding in Insulin Resistance-Prone vs. Insulin Sensitive Humans

• ClinicalTrials.gov Identifier: NCT02084641
• Recruitment Status: Unknown
• First Posted: March 12, 2014
• Last Update Posted: March 12, 2014
• Sponsor: Stanford University
• Information provided by (Responsible Party): Tracey McLaughlin, Stanford University

Study Description

Brief Summary:

Obesity has become an epidemic worldwide. Data from our laboratory and others demonstrate that most of the excess morbidity from obesity is related to insulin resistance (IR). While total adiposity correlates with insulin resistance, not all obese individuals are IR. When obese IR individuals lose weight in response to caloric restriction, even moderate loss of body fat results in improved insulin sensitivity (IS). With massive weight loss, either dietary or surgical, even the most IR individuals can completely reverse their insulin resistance. But why is one individual IR at a BMI of 26 and another IS at a BMI of 35? There must be differences in the manner in which adipose cells/tissue respond to caloric excess and weight gain. One potentially unifying hypothesis with regard to obesity-associated insulin resistance is that those individuals who fail to respond to caloric excess/obesity with adequate adipocyte differentiation and expanded subcutaneous fat storage capacity develop increased circulating FFAs, ectopic fat deposition, stress on adipocytes, triggering localized and systemic inflammation and ultimately insulin resistance in skeletal muscle.

Clearly, the best way to examine the human response to obesity is to challenge overweight individuals with the need to store excess triglyceride in adipose tissue. Specific aims are:

1. Test the hypothesis that impaired adipogenesis and fat storage capacity are associated with insulin resistance by comparing 1) cell size distribution; 2) gene markers of adipose cell differentiation; 3) differentiation of isolated preadipocytes in IR-prone vs IS individuals subjected to caloric excess.
2. Determine if circulating (daylong FFA, two-stage Insulin Suppression Test) and ectopic fat (MRI liver, CT abdomen) are worsened to a greater degree in IR-prone vs IS individuals subjected to caloric excess.
3. Determine whether differences in inflammation and/or innate or adaptive immune response are associated with insulin resistance by comparing differences in resident dendritic cells, macrophages and their activation profiles, changes in T-cell subpopulations, and other inflammatory mediators in IR-prone vs IS individuals who are subjected to caloric excess via overfeeding.
4. Exploratory: Evaluate IR-prone vs IS individuals for evidence of hypoxia and insufficient angiogenic response in response to caloric excess.

Condition or disease	Intervention/treatment	Phase
Insulin Resistance; Obesity	Other: Over feeding	Not Applicable

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 45 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Official Title: Adipose Tissue Response to Overfeeding in Insulin Resistance-Prone vs. Insulin Sensitive Humans
• Study Start Date: September 2011
• Estimated Primary Completion Date: December 2016
• Estimated Study Completion Date: December 2016

Arms and Interventions

Arm	Intervention/treatment
Experimental: Insulin resistant and insulin sensitive; Both groups will be given the same intervention and then outcomes compared between groups	Other: Over feeding; Study participants will be given low saturated fat snacks, an additional 750-1000 calories to gain 6-8 lbs over 4 weeks

Outcome Measures

Primary Outcome Measures :

1. Subcutaneous adipose cell triglyceride storage capacity/differentiation [ Time Frame: 3 years ]
   this will be quantified by measuring: 1) adipose cell size distribution; 2) gene markers of adipose cell differentiation; 3) differentiation of isolated preadipocytes in IR-prone vs IS individuals subjected to caloric excess; in vivo triglyceride synthesis using stable isotope methods

Secondary Outcome Measures :

1. Ectopic fat [ Time Frame: 3 years ]
   Fat deposited in liver (MRI), visceral (intraabdominal) abdominal (CT) versus subcutaneous abdominal and thigh fat (CT)

Other Outcome Measures:

1. Adipose tissue and systemic inflammation: both innate or adaptive immune response [ Time Frame: 3 years ]
   Flow cytometry will be used to quantitate, in both adipose tissue and plasma, populations of dendritic cells, T-cell subpopulations, and macrophages

Eligibility Criteria

• Ages Eligible for Study: 35 Years to 65 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

Inclusion Criteria:

BMI 25-35 kg/m2 Healthy adults Age 35-65 Weight stable Nondiabetic

Exclusion Criteria:

Major organ disease such as heart, kidney, liver Malignancy Inflammatory conditions (eg. lupus, rheumatoid arthritis, Crohn's disease) Eating disorder h/o bariatric surgery or liposuction use of blood thinners such as Coumadin (aspirin is ok)

Contacts and Locations

Contacts

Contact: Colleen Craig, MD; 650-736-2056

Contact: Dalia Perelman, RD; 650-723-6713

Locations

United States, California

Stanford University; Recruiting

Stanford, California, United States, 94305

Contact: Craig, MD 650-736-2056

Contact: Lamendola, NP 650-736-2056

Sponsors and Collaborators

Stanford University

Investigators

• Principal Investigator: Tracey McLaughlin, MD; Stanford University

More Information

• Responsible Party: Tracey McLaughlin, Associate Professor, Stanford University
• ClinicalTrials.gov Identifier: NCT02084641
• Other Study ID Numbers: 20281
• First Posted: March 12, 2014
• Last Update Posted: March 12, 2014
• Last Verified: March 2014

Keywords provided by Tracey McLaughlin, Stanford University:

ectopic fat; obesity; triglyceride storage; adipocyte; overfeeding; intrahepatic fat; adipocyte proliferation; inflammation; macrophage

Additional relevant MeSH terms:

Insulin Resistance; Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases