Abstract

Adipose tissue is a major endocrine organ capable of secreting adipokines with a role in whole-body metabolism. Changes in the secretome profile during the development of obesity is suspected to contribute to the risk of health complications such as those associated with weight regain after weight loss. However, the number of studies on weight regain is limited and secretome changes during weight regain have hardly been investigated. In an attempt to generate leads for in vivo studies, we have subjected human Simpson Golabi Behmel Syndrome adipocytes to glucose restriction (GR) followed by refeeding (RF) as an in vitro surrogate for weight regain after weight loss. Using LC-MS/MS, we compared the secreted protein profile after GR plus RF with that of normal feeding (NF) to assess the consequences of GR plus RF. We identified 338 secreted proteins of which 49 were described for the first time as being secreted by adipocytes. In addition, comparison between NF and GR plus RF showed 39 differentially secreted proteins. Functional classification revealed GR plus RF-induced changes of enzymes for extracellular matrix modification, complement system factors, cathepsins, and several proteins related to Alzheimer’s disease. These observations can be used as clues to investigate metabolic consequences of weight regain, weight cycling or intermittent fasting.

Highlights

  • Obesity has become a worldwide critical health issue because it is frequently accompanied by the development of health complications such as type II diabetes, cardiovascular diseases, respiratory problems and certain types of cancer [1]

  • We manually checked the list of proteins which were not recognized as secreted by SignalP or Deeploc, for proteins known by their function to be secreted

  • In the present study we focused on the secretome of those samples and searched for secreted proteins, of which the abundance was influenced by glucose restriction (GR) plus RF

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Summary

Introduction

Obesity has become a worldwide critical health issue because it is frequently accompanied by the development of health complications such as type II diabetes, cardiovascular diseases, respiratory problems and certain types of cancer [1]. Studies have shown that the secreted proteins are hormones, cytokines, extracellular matrix related proteins as well as proteins involved in cardiovascular, lipid and glucose metabolism [3]. These adipokines have a variety of effects on homeostasis and metabolism by autocrine, paracrine and endocrine activity, which could contribute to the development of obesity and obesity-associated complications [4,5]. It has been suggested that weight regain after weight loss could worsen metabolic health [10], possibly mediated by changes in the adipose tissue secretome. The number of biological studies on weight regain has been limited and secretome changes during weight regain are largely unknown

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