Meikle, M. N. | bioRxiv Science

bioRxiv2024

Adipocyte-specific deletion of Dbc1 does not recapitulate healthy obesity phenotype but suggests regulation of inflammation signaling

The protein Deleted in Breast Cancer 1 (DBC1), a regulator of several transcription factors and epigenetic modulators, plays determinant roles in metabolism regulation, obesity and aging-related processes. Knockout mice for Dbc1, develop morbid obesity but are protected against liver steatosis, insulin resistance and atherosclerosis. We have proposed that this healthy obesity phenotype was mainly due to the expansion of adipose tissue, avoiding free-fatty acid spillover and metabolic damage in peripheral tissues. To gain more insight about the role of Dbc1 in adipose cells during obesity and its impact on metabolic dysregulation, we generated a conditional Dbc1 KO mouse and backcrossed it with CRE-AdipoQ transgenic mice, aiming to abrogate Dbc1 expression in all mature adipocytes (cAT-Dbc1). cAT-Dbc1 mice showed deletion of Dbc1 specifically in mature adipocytes in different fat depots. We tested the effect of Dbc1 deletion in adipocytes on different aspects of metabolic regulation in male and female mice fed in normal chow and high-fat diets. We found that deletion of Dbc1 in mature adipocytes had no effect on weight gain, glucose tolerance and other markers of metabolic dysregulation, regardless sex. However, Dbc1 KO adipocytes displayed an mRNA expression profile consistent with increased inflammation during obesity. Our results suggest that the healthy phenotype displayed in the whole body Dbc1 KO obese mice is not due to the protein function in mature adipocytes and might involve other cell types present in adipose tissue. Instead, the specific deletion of Dbc1 in mature adipocytes highlights a novel role of Dbc1 in inflammation signaling during obesity.

physiology↗

bioRxiv2022

The lectin receptor Clec4F participates in the capture of circulating parasite mucins by Kupffer cells in cystic echinococcosis.

Cystic echinococcosis is caused by the larval stages (hydatids) of cestode parasites belonging to the species cluster Echinococcus granulosus sensu lato, with E. granulosus sensu stricto being the main infecting species. Hydatids are bladder-like structures that attain large sizes within various internal organs of livestock ungulates and humans. Hydatids are protected by the massive acellular laminated layer (LL), composed mainly by mucins. Parasite growth requires LL turnover, and abundant LL-derived particles are found at infection sites in infected humans, raising the question of how LL materials are dealt with by the hosts. In this article, we show that E. granulosus sensu stricto LL mucins injected into mice are taken up by Kupffer cells, the liver macrophages exposed to the vascular space. This uptake is largely dependent on the intact mucin glycans and on Clec4F, a C-type lectin receptor which in rodents is selectively expressed in Kupffer cells. This uptake mechanism operates on mucins injected both in soluble form i.v. and in particulate form i.p. In mice harbouring intraperitoneal infections by the same species, LL mucins were found essentially only at the infection site and in the liver, where they were taken up by Kupffer cells via Clec4F. Therefore, shed LL materials circulate in the host and Kupffer cells can act as a sink for these materials even when the parasite grows in sites other than the liver.

immunology↗