Expandability of Aging Adipose Tissue

Overview

The purpose of this pilot study is to determine whether adipose tissue loses some of its ability to expand in response to overfeeding in older compared to younger men. The investigators hypothesize that the adipose tissue response to overfeeding may be weakened in older when compared to younger men, thereby leading to worsened ectopic storage depots for older men.

Full Title of Study: “Aging Subcutaneous Adipose Tissue Response to Overfeeding”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Non-Randomized
    • Intervention Model: Single Group Assignment
    • Primary Purpose: Basic Science
    • Masking: None (Open Label)
  • Study Primary Completion Date: December 2016

Detailed Description

This pilot study will begin to address whether adipose tissue biology changes with advancing age. Specifically, we will test whether adipose tissue loses some of its ability to expand in response to overfeeding in older compared to younger men. To test this possibility the Investigators will recruit overweight and mildly obese older (age 55-75y) and younger (age 25-40y) men and collect adipose tissue biopsies before and after 7 days of overfeeding. The investigators will test how well the cells in adipose tissue expand in response to overfeeding and whether this differs between younger and older men.

Interventions

  • Other: Overfeeding
    • Consumption of 40% excess calories for 7 consecutive days

Arms, Groups and Cohorts

  • Other: MA
    • Middle-aged overweight and obese men (age 25-40yr)
  • Other: OA
    • Older overweight and obese men (age 55-75yr)

Clinical Trial Outcome Measures

Primary Measures

  • Change in adipose-derived stem cell (ASC) differentiation (Delta%oil red O+)
    • Time Frame: 1 wk of overfeeding
    • age-related difference in the ASC differentiation response to overfeeding

Secondary Measures

  • Change in ASC proliferation (Delta rate of cell growth)
    • Time Frame: 1 wk of overfeeding
    • age-related difference in the ASC proliferative response to overfeeding
  • Change in expression of C/EBPalpha, C/EBPbeta, PPARgamma2, SREBP1c, SREBf1a, and Wnt10b (fold-changes in mRNA expression)
    • Time Frame: 1 wk overfeeding
    • age-related difference in the pro-adipogenic response to overfeeding
  • Change in intramyocellular (IMCL) di-saturated diacylglycerol (DAG) localization (Delta %membrane:cytosol)
    • Time Frame: 1 week overfeeding
    • age-related difference in the IMCL DAG response to overfeeding

Participating in This Clinical Trial

Inclusion Criteria

  • Men – Aged 25-40y OR 55-75y – BMI 28-35 kg/m2 – Weight stable (±2kg over past 3 mo) – Sedentary to moderately active (<3 d/wk of exercise lasting >20min) – Non-smokers (never used or quit >7yrs prior) Exclusion Criteria:

  • Women – Currently using hormones, glucose or lipid lowering medication – Engaged in exercise or diet program – Currently gaining or losing weight or using weight loss drugs – Diabetes mellitus (diagnosis, treatment, FBG ≥126 mg/dL) – Uncontrolled metabolic disorders (e.g., thyroid)

Gender Eligibility: Male

Minimum Age: 25 Years

Maximum Age: 75 Years

Are Healthy Volunteers Accepted: Accepts Healthy Volunteers

Investigator Details

  • Lead Sponsor
    • University of Colorado, Denver
  • Collaborator
    • Colorado State University
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Official(s)
    • Rachael E Van Pelt, PhD, Principal Investigator, University of Colorado, Denver

References

Kim JY, van de Wall E, Laplante M, Azzara A, Trujillo ME, Hofmann SM, Schraw T, Durand JL, Li H, Li G, Jelicks LA, Mehler MF, Hui DY, Deshaies Y, Shulman GI, Schwartz GJ, Scherer PE. Obesity-associated improvements in metabolic profile through expansion of adipose tissue. J Clin Invest. 2007 Sep;117(9):2621-37. doi: 10.1172/JCI31021.

Caso G, McNurlan MA, Mileva I, Zemlyak A, Mynarcik DC, Gelato MC. Peripheral fat loss and decline in adipogenesis in older humans. Metabolism. 2013 Mar;62(3):337-40. doi: 10.1016/j.metabol.2012.08.007. Epub 2012 Sep 19.

Tchoukalova YD, Votruba SB, Tchkonia T, Giorgadze N, Kirkland JL, Jensen MD. Regional differences in cellular mechanisms of adipose tissue gain with overfeeding. Proc Natl Acad Sci U S A. 2010 Oct 19;107(42):18226-31. doi: 10.1073/pnas.1005259107. Epub 2010 Oct 4.

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