Glucose Restriction Plus Refeeding in Vitro Induce Changes of the Human Adipocyte Secretome with an Impact on Complement Factors and Cathepsins

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.

Endurance-Type Exercise Increases Bulk and Individual Mitochondrial Protein Synthesis Rates in Rats

“…A separate piece of muscle underwent a trypsin digestion protocol as previously described (Qiao et al, 2019) to cleave peptides. The peptide mixture was loaded onto an LC-MS/MS, configured as described previously (Qiao et al, 2019;Vogel et al, 2019).…”

The Effects of Mild Intermittent Hypoxia Exposure on the Abdominal Subcutaneous Adipose Tissue Proteome in Overweight and Obese Men: A First-in-Human Randomized, Single-Blind, and Cross-Over Study

“…Carbamidomethylation of cysteines was set as fixed modifications. Label free quantitation was conducted using the Minora Feature Detector node in the processing step and the Feature Mapper node combined with the Precursor Ions Quantifier node in the consensus step with default settings within Proteome Discoverer 2.2 ( Qiao et al, 2019 ).…”

Secretome of Adipose Tissue as the Key to Understanding the Endocrine Function of Adipose Tissue

“…One method is to replace a serum-enriched or differentiating medium with a medium devoid of glucose, insulin and serum [27]. This method does not allow for the examination of the proteins secreted during the earlier stages of the cell culture process.…”

“…In a study by Qiao et al [27], which was conducted using a peptide tagging method, 1326 proteins were identified, of which 230 were recognized by Deeploc as adipocytesecreted proteins. Signal IP detected the presence of a signal peptide in 328 proteins.…”

“…The study demonstrated that GR and RF induce adipocyte secretome changes involving biological pathways of ECM remodeling, lipid metabolism, the complement system and tissue homeostasis. Furthermore, 49 proteins secreted exclusively by adipocytes were described for the first time in the study [27].…”