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Review
. 2018 Feb;9(2):178-195.
doi: 10.1007/s13238-017-0437-z. Epub 2017 Jul 4.

Carboxylesterases in lipid metabolism: from mouse to human

Jihong Lian  1   2 , Randal Nelson  3   4 , Richard Lehner  3   4   5
Affiliations
Review

Carboxylesterases in lipid metabolism: from mouse to human

Jihong Lian et al. Protein Cell. 2018 Feb.

Abstract

Mammalian carboxylesterases hydrolyze a wide range of xenobiotic and endogenous compounds, including lipid esters. Physiological functions of carboxylesterases in lipid metabolism and energy homeostasis in vivo have been demonstrated by genetic manipulations and chemical inhibition in mice, and in vitro through (over)expression, knockdown of expression, and chemical inhibition in a variety of cells. Recent research advances have revealed the relevance of carboxylesterases to metabolic diseases such as obesity and fatty liver disease, suggesting these enzymes might be potential targets for treatment of metabolic disorders. In order to translate pre-clinical studies in cellular and mouse models to humans, differences and similarities of carboxylesterases between mice and human need to be elucidated. This review presents and discusses the research progress in structure and function of mouse and human carboxylesterases, and the role of these enzymes in lipid metabolism and metabolic disorders.

Keywords: adipose; carboxylesterase; intestine; lipase; lipid; lipoprotein; liver.

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Figures

Figure 1
Figure 1
Amino acid sequence alignments of human and murine carboxylesterases reported to hydrolyze lipids. Boxed residues indicate conserved functional residues and domains: 1, oxyanion hole-forming domain; 2, GXSXG catalytic serine motif; 3, catalytic glutamic acid; 4, catalytic histidine; NLBD, putative neutral lipid binding domain. The HXEL ER retrieval sequence is indicated with bold letters. Residues that comprise the rigid pocket on CES1 are indicated with arrows. GenBank accession numbers: CES1, NP_001257; CES2, NP_003860; CES3, NP_079198; Ces1d, NP_444430; Ces1e, NP_598421; Ces1g, NP_067431; Ces2c, NP_663578; Ces2g, NP_932116
Figure 2
Figure 2
Three-dimensional structure of human CES1
Figure 3
Figure 3
Effects of Ces1d deficiency on lipid and energy homeostasis
Figure 4
Figure 4
Effects of Ces1g deficiency on lipid and energy homeostasis
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