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

NCT02084641 | Completed

• 1 other identifier: 20281
• Study Type: interventional
• Target: 58
• Locations: 1 country
• Sites: 1

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. 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. 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. 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. 4.Exploratory: Evaluate IR-prone vs IS individuals for evidence of hypoxia and insufficient angiogenic response in response to caloric excess.

Conditions

Insulin Resistance; Obesity

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Subcutaneous adipose cell triglyceride storage capacity/differentiation

  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

  3 years

Secondary Outcomes (1)

• Ectopic fat

  3 years

Other Outcomes (1)

• Adipose tissue and systemic inflammation: both innate or adaptive immune response

  3 years

Study Arms (2)

Insulin resistant

EXPERIMENTAL

Both groups will be given the same intervention and then outcomes compared between groups

Other: Over feeding

Insulin Sensitive

EXPERIMENTAL

Both groups will be given the same intervention and then outcomes compared between groups

Other: Over feeding

Interventions

Over feeding OTHER

Study participants will be given low saturated fat snacks, an additional 750-1000 calories to gain 6-8 lbs over 4 weeks

Insulin Sensitive; Insulin resistant

Eligibility Criteria

• Age: 35 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Stanford University: lead

Study Sites (1)

Stanford University

Stanford, California, 94305, United States

Location

MeSH Terms

Conditions

Insulin Resistance; Obesity; Inflammation

Condition Hierarchy (Ancestors)

Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Overweight; Overnutrition; Nutrition Disorders; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Pathologic Processes

Study Officials

• Tracey McLaughlin, MD

  Stanford University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: March 12, 2013
• First Posted: March 12, 2014
• Study Start: September 1, 2011
• Primary Completion: August 1, 2016
• Study Completion: August 1, 2016
• Last Updated: August 14, 2023

Record last verified: 2023-08

Locations

US (1)