Tetranectin as a Novel Obesity-associated Adipokine for Regulating Lipid Accumulation

Adipose tissue is strongly correlated to obesity and diabetes which are two major problems in the worldwide. Adipose tissue is involved in modulating glucose and energy metabolism locally and systemically by secreting factors, called adipocytokines. Tetranectin (TN), a novel adipocytokine, is secreted by adipose tissues. TN may regulate the glucose/energy homeostasis to affect lipid accumulation.The role of TN in adipocytes with or without TN on regulation of adipose tissue growth and lipid metabolism is valuable to be studied.

Materials and methods: Secreted proteins from human adipocyte culture medium were deciphered using 2-D polyacrylamide gel electrophoresis and determined by LC/MS with MALDI-TOF analysis of proteins. Adipose tissues were obtained from the breast of 15 women undergoing mastectomy. Serum samples from 200 normal healthy people and 54 breast cancer patients were assigned to either a lean or obese group according to the body mass index. The TN protein concentration was measured in the culture medium of stromal-vascular fraction (SVF)-derived adipocytes from healthy humans, breast cancer patients, pigs and also from 3T3-L1 cells. Associations between plasma TN and other biomarkers were assessed with Pearson's correlations and multivariable linear regression.

Study Overview

• Status: Completed
• Conditions: Obesity; Metabolic Syndrome
• Intervention / Treatment: Genetic: Tetranectin

Detailed Description

Adipose tissues were obtained from the breast of breast cancer patients with 0 to 1 progression stage. All participants gave permission and the study was approved by the Ethics Committee of National Taiwan University Hospital as no. 9461701203.

From 2012 to 2013 in National Taiwan University Hospital, a cross-sectional sampling of 21 to 78 -year old people included women and men who were living in Taiwan. Blood samples were collected after an overnight fasting. Serum was separated by centrifugation and stored at -80 ℃ until analysis. Plasma triglyceride (TG), high density lipoprotein (HDL), low density lipoprotein (LDL), cholesterol, glucose and insulin were measured. Fasting serum samples were obtained from 193 randomly selected persons having health check-ups. To investigate the relationship among TN and breast cancer, fasting serum samples also obtained from 54 randomly selected breast cancer patients who were 25 to 59 years old with elected surgery for breast cancer stage 0 and 1.

• Study Type: Observational
• Enrollment (Actual): 289

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Adipose tissues were obtained from the breast of breast cancer patients with 0 to 1 progression stage.

Description

Inclusion Criteria:

1. Must be above age 20 years old.
2. Subjects must sign the written informed consent form.
3. Must have residual fat after surgery.
4. Clinical diagnosis of liposuction and tumor resection.

Exclusion Criteria:

1. Terminal cancer.
2. Subjects have no fat tissue after surgery.
3. Pregnant subjects.

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Only
• Time Perspectives: Retrospective

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
BMI 18-21; Tetranectin mRNA and protein level were measure in the adipose tissues which were belonging to body mass index is 18-21 kg/m2	Genetic: Tetranectin; Adipose tissues were obtained from the breast of breast cancer patients with 0 to 1 progression stage. The subjects were 33-51 y of age (mean = 43.6, SD = 6.2) with a BMI of 16-33 kg/m2 (mean = 21.5, SD = 4.5). Blood samples were collected after an overnight fasting. Serum was separated by centrifugation and stored at -80 ℃ until analysis. Plasma Tetranectin,triglyceride (TG), high density lipoprotein (HDL), low density lipoprotein (LDL), cholesterol, glucose and insulin were measured. And the tetranectin mRNA and protein level was measure in adipose tissue
BMI 33-39; Tetranectin mRNA and protein level were measure in the adipose tissues which were belonging to body mass index is 33-39 kg/m2	Genetic: Tetranectin; Adipose tissues were obtained from the breast of breast cancer patients with 0 to 1 progression stage. The subjects were 33-51 y of age (mean = 43.6, SD = 6.2) with a BMI of 16-33 kg/m2 (mean = 21.5, SD = 4.5). Blood samples were collected after an overnight fasting. Serum was separated by centrifugation and stored at -80 ℃ until analysis. Plasma Tetranectin,triglyceride (TG), high density lipoprotein (HDL), low density lipoprotein (LDL), cholesterol, glucose and insulin were measured. And the tetranectin mRNA and protein level was measure in adipose tissue
BMI 25-30; Tetranectin mRNA and protein level were measure in the adipose tissues which were belonging to body mass index is 25-30 kg/m2	Genetic: Tetranectin; Adipose tissues were obtained from the breast of breast cancer patients with 0 to 1 progression stage. The subjects were 33-51 y of age (mean = 43.6, SD = 6.2) with a BMI of 16-33 kg/m2 (mean = 21.5, SD = 4.5). Blood samples were collected after an overnight fasting. Serum was separated by centrifugation and stored at -80 ℃ until analysis. Plasma Tetranectin,triglyceride (TG), high density lipoprotein (HDL), low density lipoprotein (LDL), cholesterol, glucose and insulin were measured. And the tetranectin mRNA and protein level was measure in adipose tissue

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Tetranectin expression measure	Detect Tetranectin expression in adipose tissue by qPCR or Western blotting	through study completion, an average of 2 years

Collaborators and Investigators

• Sponsor: National Taiwan University Hospital
• Investigators: Principal Investigator: Shih-Torng Ding, Ph D, National Taiwan University

Publications and helpful links

General Publications

• Jaquinod M, Holtet TL, Etzerodt M, Clemmensen I, Thogersen HC, Roepstorff P. Mass spectrometric characterisation of post-translational modification and genetic variation in human tetranectin. Biol Chem. 1999 Nov;380(11):1307-14. doi: 10.1515/BC.1999.166.
• Iba K, Durkin ME, Johnsen L, Hunziker E, Damgaard-Pedersen K, Zhang H, Engvall E, Albrechtsen R, Wewer UM. Mice with a targeted deletion of the tetranectin gene exhibit a spinal deformity. Mol Cell Biol. 2001 Nov;21(22):7817-25. doi: 10.1128/MCB.21.22.7817-7825.2001.

Study record dates

Study Major Dates

• Study Start (Actual): December 6, 2005
• Primary Completion (Actual): December 5, 2008
• Study Completion (Actual): December 5, 2008

Study Registration Dates

• First Submitted: July 13, 2017
• First Submitted That Met QC Criteria: July 23, 2017
• First Posted (Actual): July 25, 2017

Study Record Updates

• Last Update Posted (Actual): July 28, 2017
• Last Update Submitted That Met QC Criteria: July 25, 2017
• Last Verified: December 1, 2005

More Information

Terms related to this study

• Keywords: adipokine, tetranectin, lipid metabolism, body mass index
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Overnutrition; Nutrition Disorders; Overweight; Body Weight; Insulin Resistance; Hyperinsulinism; Obesity; Metabolic Syndrome
• Other Study ID Numbers: 9461701203

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided
• IPD Plan Description: Serum samples and adipose tissue from breast cancer patients were assigned to either a lean or obese group according to the body mass index. The TN protein concentration was measured in the serum samples and culture medium of stromal-vascular fraction (SVF)-derived adipocytes from breast cancer patients,

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No