Physiological response of adipocytes to weight loss and maintenance.

Background: Metabolic processes in adipose tissue are dysregulated in obese subjects and, in response to weight loss, either normalize or change in favor of weight regain.

Objective: To determine changes in adipocyte glucose and fatty acid metabolism in relation to changes in adipocyte size during weight loss and maintenance.

Methods: Twenty-eight healthy subjects (12 males), age 20-50 y, and BMI 28-35 kg/m(2), followed a very low energy diet for 2 months, followed by a 10-month period of weight maintenance. Body weight, body composition (deuterium dilution and BodPod), protein levels (Western blot) and adipocyte size were assessed prior to and after weight loss and after the 10-month follow-up.

Results: A 10% weight loss resulted in a 16% decrease in adipocyte size. A marker for glycolysis decreased (AldoC) during weight loss in association with adipocyte shrinking, and remained decreased during follow-up in association with weight maintenance. A marker for fatty acid transport increased (FABP4) during weight loss and remained increased during follow-up. Markers for mitochondrial beta-oxidation (HADHsc) and lipolysis (ATGL) were only increased after the 10-month follow-up. During weight loss HADHsc and ATGL were coordinately regulated, which became weaker during follow-up due to adipocyte size-related changes in HADHsc expression. AldoC was the major denominator of adipocyte size and body weight, whereas changes in ATGL during weight loss contributed to body weight during follow-up. Upregulation of ATGL and HADHsc occured in the absence of a negative energy balance and was triggered by adipocyte shrinkage or indicated preadipocyte differentiation.

Conclusion: Markers for adipocyte glucose and fatty acid metabolism are changed in response to weight loss in line with normalization from a dysregulated obese status to an improved metabolic status.

Trial Registration: ClinicalTrials.gov NCT01015508.