three-dimensional-adipocyte-culture-as-model-to-study-cachexia

Three-Dimensional Adipocyte Culture as a Model to Study Cachexia-Induced White Adipose Tissue Remodeling

Cancer cachexia (CC) presents itself as a syndrome with multiple manifestations, causing a marked multi-organ metabolic imbalance. Recently, cachectic ...

Boston University School of Medicine

Animal lifespan is controlled through genetic pathways that are conserved from nematodes to humans. Lifespan-promoting conditions in nematodes include fasting and a reduction of insulin/IGF signaling. Here we aimed to investigate the input of the Caenorhabditis elegans homologue of the mammalian rate-limiting lipolytic enzyme Adipose Triglyceride Lipase, ATGL-1, in longevity control.

ATGL-1 mediates the effect of dietary restriction and the insulin/IGF-1 signaling pathway on longevity in C. elegans.

White adipose tissue (WAT) is a dynamic tissue, which responds to environmental stimuli and dietary cues by changing its morphology and metabolic capacity. The ability of WAT to undergo a beige remodeling has become an appealing strategy to combat obesity and its comorbidities. Here, by using single-cell RNA sequencing, we provide a comprehensive atlas of the cellular dynamics during beige remodeling. We reveal drastic changes both in the overall cellular composition and transcriptional states of individual cell subtypes between Adrb3- and cold-induced beiging. Moreover, we demonstrate that cold induces a myeloid to lymphoid shift of the immune compartment compared to Adrb3 activation. Further analysis showed that, Adrb3 stimulation leads to activation of the interferon/Stat1 pathways favoring infiltration of myeloid immune cells, while repression of this pathway by cold promotes lymphoid immune cell recruitment. These findings highlight that pharmacological mimetics may not provide the same beneficial effects as physiological stimuli.

Article	Year
ATGL-1 mediates the effect of dietary restriction and the insulin/IGF-1 signaling pathway on longevity in C. elegans. Molecular metabolism\| PubMed ID: 31311719	2019
Shifts of Immune Cell Populations Differ in Response to Different Effectors of Beige Remodeling of Adipose Tissue. iScience\| PubMed ID: 33294778	2020

Kathleen Desevin

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