Wnt10b Participates in Regulating Fatty Acid Synthesis in the Muscle of Zebrafish

Abstract

There are 19 Wnt genes in mammals that belong to 12 subfamilies. Wnt signaling pathways participate in regulating numerous homeostatic and developmental processes in animals. However, the function of Wnt10b in fatty acid synthesis remains unclear in fish species. In the present study, we uncovered the role of the Wnt10b signaling pathway in the regulation of fatty acid synthesis in the muscle of zebrafish. The gene of Wnt10b was overexpressed in the muscle of zebrafish using pEGFP-N1-Wnt10b vector injection, which significantly decreased the expression of glycogen synthase kinase 3β (GSK-3β), but increased the expression of β-catenin, peroxisome proliferators-activated receptor γ (PPARγ), and CCAAT/enhancer binding protein α (C/EBPα). Moreover, the activity and mRNA expression of key lipogenic enzymes ATP-citrate lyase (ACL), acetyl-CoA carboxylase (ACC) and fatty acid synthetase (FAS), and the content of non-esterified fatty acids (NEFA), total cholesterol (TC), and triglyceride (TG) were also significantly decreased. Furthermore, interference of the Wnt10b gene significantly inhibited the expression of β-catenin, PPARγ, and C/EBPα, but significantly induced the expression of GSK-3β, FAS, ACC, and ACL. The content of NEFA, TC, and TG as well as the activity of FAS, ACC, and ACL significantly increased. Thus, our results showed that Wnt10b participates in regulating fatty acid synthesis via β-catenin, C/EBPα and PPARγ in the muscle of zebrafish.

WNT/β‐catenin pathway is a key regulator of cardiac function and energetic metabolism

“…238,239 Canonical WNT signaling determines the fate of muscle progenitor cells, directing their differentiation in myofibrils, whereas its inhibition shifts differentiation in an adipogenic direction, leading to muscle steatosis through evolutionarily conserved activation of the lipogenic sterol regulatory-element binding protein 1 pathway. [240][241][242][243] Arrhythmogenic right ventricular cardiomyopathy is a hereditable disease that is caused by mutations of desmosomal proteins. 244 Desmosome disruption leads to liberation of the βcatenin homolog plakoglobin and its translocation to the nucleus, where plakoglobin competes with βcatenin for the TCF4 transcription co-activator.…”

“…Bones are metabolically active organs that regulate whole‐body metabolism through β‐catenin‐driven FA β‐oxidation 238,239 . Canonical WNT signaling determines the fate of muscle progenitor cells, directing their differentiation in myofibrils, whereas its inhibition shifts differentiation in an adipogenic direction, leading to muscle steatosis through evolutionarily conserved activation of the lipogenic sterol regulatory‐element binding protein 1 pathway 240–243 …”

The role of WNT10B in physiology and disease: A 10-year update

“…Wnt10b in muscle has also been studied in the zebrafish model. Wnt10b signaling inhibits the synthesis of fatty acids in zebrafish myocytes ( Liu D. et al, 2019 ). Knockdown of Wnt10b mRNA led to an increase in triglyceride, total cholesterol, and non-esterified fatty acids in the muscle and corresponding increases in the expression of fatty acid synthetase, acetyl-CoA carboxylase, and ATP-citrate lyase.…”

Dietary iron affects lipid deposition, nutritional element, and muscle quality in coho salmon (Oncorhynchus kisutch)

“…The fatty acids synthesis enzymes, mainly including ACC, ACL and FAS, play a crucial role in regulating lipid metabolism and lipid deposition ( Gu et al, 2019 , Liu et al, 2019 ). In this study, we discovered that the suitable dietary Fe content decreased ACC, ACL, and FAS activity as well as TG content.…”