Chromosomal localization of lipolytic enzymes in the mouse: pancreatic lipase, colipase, hormone-sensitive lipase, hepatic lipase, and carboxyl ester lipase

Warden, Craig H; Davis, Richard C.; Yoon, Moon-Young; Hui, David Y.; Svenson, Karen L.; Xia, Yu‐Rong; Diep, Anh; He, Kongyuan; Lusis, Aldons J.

doi:10.1016/s0022-2275(20)36974-1

Cited by 36 publications

(7 citation statements)

References 24 publications

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“…Mice homozygous for the mutation synthesize normal levels of lipase protein that is inactive and retained intracellularly (24 -26). The mutation does not affect the lipase coding sequence, as cld does not co-localize with the lipase structural genes (27,28). Rather, it has been proposed that cld might interfere with early glycan modification events, or with the course of lipase folding carried out in conjuncture with these events (21).…”

mentioning

confidence: 99%

cld and lec23 are disparate mutations that affect maturation of lipoprotein lipase in the endoplasmic reticulum

Briquet-Laugier¹,

Ben-Zeev²,

White

et al. 1999

Journal of Lipid Research

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The mutations cld (combined lipase deficiency) and lec23 disrupt in a similar manner the expression of lipoprotein lipase (LPL). Whereas cld affects an unknown gene, lec23 abolishes the activity of ␣ -glucosidase I, an enzyme essential for proper folding and assembly of nascent glycoproteins. The hypothesis that cld , like lec23 , affects the folding/assembly of nascent LPL was confirmed by showing that in cell lines homozygous for these mutations (Cld and Lec23, respectively), the majority of LPL was inactive, displayed heterogeneous aggregation, and had a decreased affinity for heparin. While inactive LPL was retained in the ER, a small amount of LPL that had attained a native conformation was transported through the Golgi and secreted. Thus, Cld and Lec23 cells recognized and retained the majority of LPL as misfolded, maintaining the standard of quality control. Examination of candidate factors affecting protein maturation, such as glucose addition and trimming, proteins involved in lectin chaperone cycling, and other abundant ER chaperones, revealed that calnexin levels were dramatically reduced in livers from cld/cld mice; this finding was also confirmed in Cld cells. We conclude that cld may affect components in the ER, such as calnexin, that play a role in protein maturation. Whether the reduced calnexin levels per se contribute to the LPL deficiency awaits confirmation. -Briquet-Laugier, V., O. Ben-Zeev, A. White, and M. H. Doolittle. cld and lec23 are disparate mutations that affect maturation of lipoprotein lipase in the endoplasmic reticulum.

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mentioning

confidence: 99%

cld and lec23 are disparate mutations that affect maturation of lipoprotein lipase in the endoplasmic reticulum

Briquet-Laugier¹,

Ben-Zeev²,

White

et al. 1999

Journal of Lipid Research

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“…Since magro is a lipase A homolog in mice, we then determined whether the transcription of lipases in mice was regulated by RU486. There are more than a dozen lipases encoded by the mice genome (Warden et al, 1993). These lipases often exhibit a clear tissue-specific expression pattern.…”

Section: Ru486 Blocks Lipid Uptake By Inhibiting Transcription Of Pnlip In Pancreasmentioning

confidence: 99%

Mifepristone (RU486) inhibits dietary lipid digestion by antagonizing the role of glucocorticoid receptor on lipase transcription

Zhang

Liang

et al. 2021

iScience

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Lipid digestion and absorption are tightly regulated to cope with metabolic demands among tissues. How these processes are coordinated is not well characterized. Here, we found that mifepristone (RU486) prevents lipid digestion both in flies and mice. In flies, RU486 administration suppresses lipid digestion by transcriptional downregulating Magro in guts. Similarly, intestinal lipid uptake in mice was also suppressed by RU486 through the glucocorticoid receptor (GR). Further studies showed that the pancreatic lipase Pnlip is a direct transcriptional target of GR in pancreas tissues. Glucocorticoid levels in mice fed a high fat diet (HFD) are significantly lower than those fed on a conventional diet, and RU486 administration inhibits HFD-induced obesity both in mice and flies. Our findings identified a novel mechanism of RU486 functions as a GR antagonist systematically regulating lipid metabolism, providing new insight on the role of Glucocorticoid/GR in Cushing disease, diabetes, and other related metabolic syndromes.

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“…Mice homozygous for the cld gene develop severe chylomicronemia on suckling and die within 72 h of birth. The cld locus maps to mouse chromosome 17 (5) and is unrelated to the LPL and HL structural loci (7). Cld thus provides a unique tool with which to analyze the specific factors that regulate levels of LPL and HL activity.…”

mentioning

confidence: 99%

Differential effect of combined lipase deficiency (cld/cld) on human hepatic lipase and lipoprotein lipase secretion

Boedeker

Doolittle²,

White

2001

Journal of Lipid Research

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Combined lipase deficiency (cld) is a recessively inherited disorder in mice associated with a deficiency of LPL and hepatic lipase (HL) activity. LPL is synthesized in cld tissues but is retained in the endoplasmic reticulum (ER), whereas mouse HL (mHL) is secreted but inactive. In this study we investigated the effect of cld on the secretion of human HL (hHL) protein mass and activity. Differentiated liver cell lines were derived from cld mice and their normal heterozygous (het) littermates by transformation of hepatocytes with SV40 large T antigen. After transient transfection with lipase expression constructs, secretion of hLPL activity from cld cells was only 12% of that from het cells. In contrast, the rate of secretion of hHL activity and protein mass per unit of expressed hHL mRNA was identical for the two cell lines. An intermediate effect was observed for mHL, with a 46% reduction in secretion of activity from cld cells. The ER glucosidase inhibitor, castanospermine, decreased secretion of both hLPL and hHL from het cells by ϳ 70%, but by only ϳ 45% from cld cells. This is consistent with data suggesting that cld may result from a reduced concentration of the ER chaperone calnexin. In conclusion, our results demonstrate a differential effect of cld on hLPL, mHL, and hHL secretion, suggesting differential requirements for activation and exit of the enzymes from the ER. -Boedeker, J. C., M. H. Doolittle, and A. L. White. Differential effect of combined lipase deficiency ( cld / cld ) on human hepatic lipase and lipoprotein lipase secretion. J.

show abstract

Chromosomal localization of lipolytic enzymes in the mouse: pancreatic lipase, colipase, hormone-sensitive lipase, hepatic lipase, and carboxyl ester lipase

Cited by 36 publications

References 24 publications

cld and lec23 are disparate mutations that affect maturation of lipoprotein lipase in the endoplasmic reticulum

cld and lec23 are disparate mutations that affect maturation of lipoprotein lipase in the endoplasmic reticulum

Mifepristone (RU486) inhibits dietary lipid digestion by antagonizing the role of glucocorticoid receptor on lipase transcription

Differential effect of combined lipase deficiency (cld/cld) on human hepatic lipase and lipoprotein lipase secretion

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