Generation of a Novel Transgenic Zebrafish for Studying Adipocyte Development and Metabolic Control

Mao, Yousheng; Hong, KwangHeum; Liao, Weifang; Li, Li; Kim, Seong‐Jin; Xiong, Yinyi; Nam, In-Koo; Choe, Seong-Kyu; Kwak, SeongAe

doi:10.3390/ijms22083994

Cited by 4 publications

(4 citation statements)

References 25 publications

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“…Although co-culture systems in fish remain to be developed, transgenic lines appeared in zebrafish that helped following in vivo adipocyte differentiation processes or adiposity dynamics ( 309 ), through the imaging of adipocyte- or lipid droplet-specific labels (fabp4-EGFP ( 310 );; plin2-TOMATO ( 311 );). Together with the use of a fasting-refeeding experiment (fabp11-EGFP ( 312 );) or a high fat diet ( 311 ) these lines helped reporting on the metabolic regulations that impact on adipose tissues.…”

Section: New Approaches To Specific Analysis Of Tissue Interactionsmentioning

confidence: 99%

Recent advances in the crosstalk between adipose, muscle and bone tissues in fish

et al. 2023

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Control of tissue metabolism and growth involves interactions between organs, tissues, and cell types, mediated by cytokines or direct communication through cellular exchanges. Indeed, over the past decades, many peptides produced by adipose tissue, skeletal muscle and bone named adipokines, myokines and osteokines respectively, have been identified in mammals playing key roles in organ/tissue development and function. Some of them are released into the circulation acting as classical hormones, but they can also act locally showing autocrine/paracrine effects. In recent years, some of these cytokines have been identified in fish models of biomedical or agronomic interest. In this review, we will present their state of the art focusing on local actions and inter-tissue effects. Adipokines reported in fish adipocytes include adiponectin and leptin among others. We will focus on their structure characteristics, gene expression, receptors, and effects, in the adipose tissue itself, mainly regulating cell differentiation and metabolism, but in muscle and bone as target tissues too. Moreover, lipid metabolites, named lipokines, can also act as signaling molecules regulating metabolic homeostasis. Regarding myokines, the best documented in fish are myostatin and the insulin-like growth factors. This review summarizes their characteristics at a molecular level, and describes both, autocrine effects and interactions with adipose tissue and bone. Nonetheless, our understanding of the functions and mechanisms of action of many of these cytokines is still largely incomplete in fish, especially concerning osteokines (i.e., osteocalcin), whose potential cross talking roles remain to be elucidated. Furthermore, by using selective breeding or genetic tools, the formation of a specific tissue can be altered, highlighting the consequences on other tissues, and allowing the identification of communication signals. The specific effects of identified cytokines validated through in vitro models or in vivo trials will be described. Moreover, future scientific fronts (i.e., exosomes) and tools (i.e., co-cultures, organoids) for a better understanding of inter-organ crosstalk in fish will also be presented. As a final consideration, further identification of molecules involved in inter-tissue communication will open new avenues of knowledge in the control of fish homeostasis, as well as possible strategies to be applied in aquaculture or biomedicine.

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Section: New Approaches To Specific Analysis Of Tissue Interactionsmentioning

confidence: 99%

Recent advances in the crosstalk between adipose, muscle and bone tissues in fish

et al. 2023

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“…Thus, the expression pattern of fabp4a(-2.7):EGFPcaax recapitulates primarily the adipose tissue domain of the endogenous expression pattern of fabp4a. Interestingly, a recent report has shown that the 1.5 kb proximal region of fabp4a directing the expression of cytoplasmic EGFP, also results in an expression pattern restricted to adipose tissue ( Mao et al, 2021 ).…”

Section: Discussionmentioning

confidence: 99%

Insights into in vivo adipocyte differentiation through cell-specific labeling in zebrafish

et al. 2021

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White adipose tissue hyperplasia has been shown to be crucial for handling excess energy in healthy ways. Though adipogenesis mechanisms have been underscored in vitro, we lack information on how tissue and systemic factors influence the differentiation of new adipocytes. While this could be studied in zebrafish, adipocyte identification currently relies on neutral lipid labeling, thus precluding access to cells in early stages of differentiation. Here we report the generation and analysis of a zebrafish line with the transgene fabp4a(-2.7):EGFPcaax. In vivo confocal microscopy of the pancreatic and abdominal visceral depots of transgenic larvae, revealed the presence of labeled mature adipocytes as well as immature cells in earlier stages of differentiation. Through co-labeling for blood vessels, we observed a close interaction of differentiating adipocytes with endothelial cells through cell protrusions. Finally, we implemented hyperspectral imaging and spectral phasor analysis in Nile Red labeled transgenic larvae and revealed the lipid metabolic transition towards neutral lipid accumulation of differentiating adipocytes. Altogether our work presents the characterization of a novel adipocyte-specific label in zebrafish and uncovers previously unknown aspects of in vivo adipogenesis.

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“…Some examples include visualizing liver, 64 pancreas, 65 and intestinal 66 development, as well as adipose tissue. 67 Fluorescently labeling entire organs or specific cell types facilitates studies of organ development, as labeled cells can be followed over time. Further, in vivo imaging with fluorescent reporter lines makes it possible to investigate cellular processes in real time.…”

Section: Zebrafish As Model Organism For Lipoprotein Researchmentioning

confidence: 99%

Zebrafish ApoB-Containing Lipoprotein Metabolism: A Closer Look

Moll,

Farber

2024

ATVB

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Zebrafish have become a powerful model of mammalian lipoprotein metabolism and lipid cell biology. Most key proteins involved in lipid metabolism, including cholesteryl ester transfer protein, are conserved in zebrafish. Consequently, zebrafish exhibit a human-like lipoprotein profile. Zebrafish with mutations in genes linked to human metabolic diseases often mimic the human phenotype. Zebrafish larvae develop rapidly and externally around the maternally deposited yolk. Recent work revealed that any disturbance of lipoprotein formation leads to the accumulation of cytoplasmic lipid droplets and an opaque yolk, providing a visible phenotype to investigate disturbances of the lipoprotein pathway, already leading to discoveries in microsomal triglyceride transfer protein and ApoB (apolipoprotein B). By 5 days of development, the digestive system is functional, making it possible to study fluorescently labeled lipid uptake in the transparent larvae. These and other approaches enabled the first in vivo description of the STAB (stabilin) receptors, showing lipoprotein uptake in endothelial cells. Various zebrafish models have been developed to mimic human diseases by mutating genes known to influence lipoproteins (eg, ldlra , apoC2 ). This review aims to discuss the most recent research in the zebrafish ApoB-containing lipoprotein and lipid metabolism field. We also summarize new insights into lipid processing within the yolk cell and how changes in lipid flux alter yolk opacity. This curious new finding, coupled with the development of several techniques, can be deployed to identify new players in lipoprotein research directly relevant to human disease.

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Generation of a Novel Transgenic Zebrafish for Studying Adipocyte Development and Metabolic Control

Cited by 4 publications

References 25 publications

Recent advances in the crosstalk between adipose, muscle and bone tissues in fish

Recent advances in the crosstalk between adipose, muscle and bone tissues in fish

Insights into in vivo adipocyte differentiation through cell-specific labeling in zebrafish

Zebrafish ApoB-Containing Lipoprotein Metabolism: A Closer Look

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