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TRIB3 Is Highly Expressed in the Adipose Tissue of Obese Patients and Is Associated With Insulin Resistance

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Abstract
Context: The upregulation of TRIB3 (Tribbles homolog 3), a stress-inducible gene
encoding a pseudokinase, has been implicated in the development of insulin resistance
in the skeletal muscle and liver of patients with obesity and type 2 diabetes. However,
there is little information regarding TRIB3 expression in human adipose tissue.
Objective: To investigate whether TRIB3 expression is dysregulated in human adipose
tissue in the context of obesity and type 2 diabetes and whether TRIB3 expression in
adipose tissues is associated with insulin resistance.
Methods: We measured metabolic parameters and TRIB3 expression in abdominal
subcutaneous and visceral adipose tissue in obese (with or without type 2 diabetes)and normal-weight women. Regulation of TRIB3 expression was studied in human
adipocytes.
Results: TRIB3 expression in both fat depots was higher in patients with obesity and/or
type 2 diabetes; in addition, the expression level was significantly associated with insulin
resistance. Incubating adipocytes under conditions mimicking the microenvironment of
obese adipose tissue, including increased endoplasmic reticulum (ER) stress, induced TRIB3
expression. In human adipocytes, the overexpression of TRIB3 impaired insulin-stimulated
protein kinase B (AKT) phosphorylation and caused dysregulation of the transcription of
genes encoding bioactive molecules released from adipocytes, such as proinflammatory
cytokines, adiponectin, and leptin. Pioglitazone, an insulin-sensitizing agent, reduced both
these effects of TRIB3 and the ER stressor?induced expression of TRB3.
Conclusion: Our data indicate that TRIB3 expression in adipose tissue is enhanced in
patients with obesity and suggest that increased TRIB3 dysregulates adipocyte function,
which may contribute to the development of insulin resistance.
Author(s)
김동욱김종혁김지민박찬윤박혜순이슬기이연지장연진최한석허윤석홍준표
Issued Date
2021
Type
Article
Keyword
TRIB3obesityadipose tissueinsulin resistancetype 2 diaetes
DOI
10.1210/clinem/dgab780
URI
https://oak.ulsan.ac.kr/handle/2021.oak/8496
https://ulsan-primo.hosted.exlibrisgroup.com/primo-explore/fulldisplay?docid=TN_cdi_proquest_miscellaneous_2591209764&context=PC&vid=ULSAN&lang=ko_KR&search_scope=default_scope&adaptor=primo_central_multiple_fe&tab=default_tab&query=any,contains,TRIB3%20Is%20Highly%20Expressed%20in%20the%20Adipose%20Tissue%20of%20Obese%20Patients%20and%20Is%20Associated%20With%20Insulin%20Resistance&offset=0&pcAvailability=true
Publisher
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
Location
미국
Language
영어
ISSN
0021-972X
Citation Volume
1
Citation Number
1
Citation Start Page
1
Citation End Page
17
Appears in Collections:
Medicine > Medicine
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