Assessing the effect of overfeeding on adipocyte and hepatic triglyceride metabolism and cell proliferation in obese insulin sensitive patients

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: SUN 690-701-Obesity Pathophysiology
Translational
Sunday, June 16, 2013: 1:45 PM-3:45 PM
Expo Halls ABC (Moscone Center)

Poster Board SUN-696
Tracey L McLaughlin1 and Candice A Allister*2
1Stanford University School of Medicine, Stanford, CA, 2University of California, Berkeley, Berkeley, CA
Assessing the effect of overfeeding on adipocyte and hepatic triglyceride metabolism and cell proliferation in obese insulin sensitive patients

Candice A. Allister, Cindy A. Lamendola, Colleen M. Craig, Samuel Cushman, Marc K Hellerstein and Tracey L. McLaughlin

Obesity is a well-established risk factor for insulin resistance, but some obese patients are able to remain insulin sensitive1.  In a current study, we have applied our technique of in vivo 2H2O labeling to show that obese insulin sensitive patients have greater triglyceride (TG) synthesis and de novo lipogenesis (DNL) in their adipocytes, compared to obese insulin resistance patients.   This phenotype suggests normal adipocyte function and a greater capacity for lipid storage protects against obesity-induced insulin resistance.  Therefore, we hypothesized that insulin sensitive subjects would be able to tolerate excess caloric intake by increasing TG synthesis and DNL in their subcutaneous adipocytes.    We explored this hypothesis using our laboratory’s technique of administering 2H2O for the quantitative measurement of triglyceride turnover, de novo lipogenesis (DNL) and cell proliferation in adipocytes.  Three obese insulin sensitive subjects consumed 2H2O for four weeks for a baseline quantification of adipocyte TG synthesis, DNL, hepatic DNL, adipocyte and stromal vascular cell (SVC) proliferation.  Subjects continued drinking 2H2O for an additional four weeks during which they consumed an additional 1000 calories per day.  The average weight gain as a result of overfeeding was 3.5kg, which was also paired with the onset of insulin resistance.  Quantitative analysis showed either an increase or no change in TG and DNL occurring in the adipocytes of overfed obese IS subjects.  There was a slight decrease in hepatic DNL, but this decrease was insignificant.  Lastly, there was a surprising and significant decrease in adipocyte and SVC proliferation in these overfed subjects.  This suggests that while some obese subjects are able to remain insulin sensitive, stressing the capacity of adipocyte function may be one mechanism by which insulin resistance manifests in once-healthy patients. 

1. Abbasi, Fahim, James W. Chu, Cindy Lamendola, Tracey McLaughlin, Hayden, Gerald Reaven and Peter D. Reaven.  “Discrimination between obesity and insulin resistance in the relationship with adiponectin.”  Diabetes, Vol 53, 2004: 585-590.

1. Abbasi, Fahim, James W. Chu, Cindy Lamendola, Tracey McLaughlin, Hayden, Gerald Reaven and Peter D. Reaven.  “Discrimination between obesity and insulin resistance in the relationship with adiponectin.”  Diabetes, Vol 53, 2004: 585-590.

Nothing to Disclose: TLM, CAA

*Please take note of The Endocrine Society's News Embargo Policy at http://www.endo-society.org/endo2013/media.cfm