Weight loss-induced changes in adipose tissue proteins associated with fatty acid and glucose metabolism correlate with

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RESEARCH

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Weight loss-induced changes in adipose tissue proteins associated with fatty acid and glucose metabolism correlate with adaptations in energy expenditure Stefan G. J. A. Camps*, Sanne P. M. Verhoef, Nadia Roumans, Freek G. Bouwman, Edwin C. M. Mariman and Klaas R. Westerterp

Abstract Background: Energy restriction causes adaptations in energy expenditure (total-,TEE; resting-,REE; activity induced-,AEE). Objective: To determine if changes in the levels of proteins involved in adipocyte glucose and fatty acid metabolism as indicators for energy deficiency are related to adaptations in energy expenditure during weight loss. Methods: Forty-eight healthy subjects (18 men, 30 women), mean ± SD age 42 ± 8 y and BMI 31.4 ± 2.8 kg/m2, followed a very low energy diet for 8 wk. Protein levels of fatty acid binding protein 4 (FABP4), fructosebisphosphate aldolase C (AldoC) and short chain 3-hydroxyacyl-CoA dehydrogenase (HADHsc) (adipose tissue biopsy, western blot), TEE (doubly labeled water), REE (ventilated hood), and AEE were assessed before and after the 8-wk diet. Results: There was a positive correlation between the decrease in AldoC and the decrease in TEE (R = 0.438, P < 0.01) and the decrease change in AEE (R = 0.439, P < 0.01). Furthermore, there was a negative correlation between the increases in HADHsc and the decrease in REE (R = 0.343, P < 0.05). Conclusion: The decrease in AldoC correlated with the decrease in AEE, which may be explained by a decreased glycolytic flux. Additionally, the change in HADHsc, a crucial enzyme for a step in beta-oxidation, correlated with the adaptation in REE. Trial registration: Clinical Trial Registration Number: NCT01015508 at clinicaltrials.gov Keywords: Energy expenditure, Physical activity, Body composition, Adipose tissue, Glucose metabolism, Fatty acid metabolism

Introduction The increasing prevalence of obesity and its comorbidities is one of the major health problems in our modern world [1]. Although weight loss strategies target both sides of the energy balance, intake and expenditure, the success of long-term weight loss maintenance is low [2, 3]. Adipose tissue is an important energy storing and releasing tissue and to fulfill this role * Correspondence: [email protected] Department of Human Biology, Nutrition and Toxicology Research Institute Maastricht, Maastricht University, PO Box 6166200 MD Maastricht, The Netherlands

adipocytes need to respond quickly to variations in the demand. Many studies have linked obesity to metabolic processes on a whole-body level, like reduced fat oxidation, as well as inside the adipocyte like a reduced metabolism of long chain fatty acids [4–7]. Studies on weight loss indicate that energy restriction results in changes in the expression of genes involved in lipid, carbohydrate and energy metabolism in adipose tissue [8–13]. During energy restriction, the limiting glucose availability must be compensated by an increased mitochondrial fatty acid oxidation to

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