Mice lacking DGKε show increased beige adipogenesis in visceral white adipose tissue after long-term high fat diet in a COX-2- dependent manner

Tomoyuki Nakano; Matthew K Topham; Kaoru Goto

doi:10.1016/j.jbior.2019.100659

Mice lacking DGKε show increased beige adipogenesis in visceral white adipose tissue after long-term high fat diet in a COX-2- dependent manner

Adv Biol Regul. 2020 Jan:75:100659. doi: 10.1016/j.jbior.2019.100659. Epub 2019 Oct 5.

Authors

Tomoyuki Nakano¹, Matthew K Topham², Kaoru Goto³

Affiliations

¹ Department of Anatomy and Cell Biology, Yamagata University School of Medicine, 2-2-2 Iida-Nishi, Yamagata City, Yamagata, 9909585, Japan. Electronic address: t-nakano@med.id.yamagata-u.ac.jp.
² Huntsman Cancer Institute, University of Utah, 2000 Circle of Hope, Salt Lake City, UT, 84112, USA.
³ Department of Anatomy and Cell Biology, Yamagata University School of Medicine, 2-2-2 Iida-Nishi, Yamagata City, Yamagata, 9909585, Japan.

PMID: 31607681
DOI: 10.1016/j.jbior.2019.100659

Abstract

Adipose tissue is a central site for energy storage in the form of triglyceride (TG). Under excess energy conditions, TG is synthesized by acylation of diacylglycerol (DG), whereas TG is broken down into DG and free fatty acid, which provide energy for mitochondrial lipid oxidation when needed. In this regard, DG is not merely an intermediate metabolite for TG metabolism; it also serves as a signaling molecule. DG kinase (DGK) phosphorylates DG to produce phosphatidic acid (PA). Consequently, DGK plays a pivotal role in the control of lipid metabolism and signal transduction pathway. Recently, a report has described that DGKε-knockout (KO) mice show expansion of epididymal white adipose tissue (WAT) together with the impairment of glucose clearance after short-term (40 days) high fat diet (HFD) feeding, an early presymptomatic phase of obesity in wild-type animals. Nevertheless, no report describes an investigation of their phenotype under long-term HFD feeding conditions. Remarkably, results obtained during long-term HFD feeding show that WAT mass is decreased significantly and that the blood glucose profile in response to glucose challenge is improved in DGKε-KO mice compared with wild-type, which contrast sharply against the phenotype shown for short-term HFD feeding. Morphological examination reveals that cyclooxygenase-2 (COX-2) expression and clusters of uncoupling protein 1 (UCP1)-positive multilocular brown-like ("beige") adipocyte are induced in DGKε-deficient WAT after long-term HFD feeding, suggesting that beige adipocytes facilitate energy expenditure during prolonged HFD feeding. Administration of celecoxib, a selective inhibitor of COX-2, abolishes the appearance of UCP1-positive beige adipocytes in DGKε-KO mice. These findings suggest that DGKε deficiency promotes visceral WAT remodeling in a COX-2-dependent manner under long-term HFD feeding conditions.

Keywords: Beiging; Cyclooxygenase-2; Diacylglycerol kinase epsilon; Epididymal white adipose tissue; High fat diet; Uncoupling protein 1.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adipogenesis* / drug effects
Adipogenesis* / genetics
Adipose Tissue, Beige / enzymology*
Animals
Cyclooxygenase 2 / genetics
Cyclooxygenase 2 / metabolism*
Diacylglycerol Kinase / deficiency*
Diacylglycerol Kinase / metabolism
Dietary Fats / pharmacology*
Intra-Abdominal Fat / enzymology*
Mice
Mice, Knockout

Substances

Dietary Fats
Ptgs2 protein, mouse
Cyclooxygenase 2
Diacylglycerol Kinase