PUBLICATION

Bmp8a deletion leads to obesity through regulation of lipid metabolism and adipocyte differentiation

Authors

Zhong, S., Chen, L., Li, X., Wang, X., Ji, G., Sun, C., Liu, Z.

ID

ZDB-PUB-230810-57

Date

2023

Source

Communications biology 6: 824824 (Journal)

Registered Authors

Liu, Zhenhui

Keywords

none

MeSH Terms

Zebrafish/genetics
Zebrafish/metabolism
Fatty Acids/metabolism
NF-kappa B/metabolism
3T3-L1 Cells
Lipid Metabolism*/genetics
Adipocytes*/metabolism
Animals
PPAR gamma/metabolism
Obesity*/metabolism
Cell Differentiation/genetics
Mice
Bone Morphogenetic Proteins*/genetics
Zebrafish Proteins/genetics

(all 14)

PubMed

37553521 Full text @ Commun Biol

Abstract

The role of bone morphogenetic proteins (BMPs) in regulating adipose has recently become a field of interest. However, the underlying mechanism of this effect has not been elucidated. Here we show that the anti-fat effect of Bmp8a is mediated by promoting fatty acid oxidation and inhibiting adipocyte differentiation. Knocking out the bmp8a gene in zebrafish results in weight gain, fatty liver, and increased fat production. The bmp8a^-/- zebrafish exhibits decreased phosphorylation levels of AMPK and ACC in the liver and adipose tissues, indicating reduced fatty acid oxidation. Also, Bmp8a inhibits the differentiation of 3T3-L1 preadipocytes into mature adipocytes by activating the Smad2/3 signaling pathway, in which Smad2/3 binds to the central adipogenic factor PPARγ promoter to inhibit its transcription. In addition, lentivirus-mediated overexpression of Bmp8a in 3T3-L1 cells significantly increases NOD-like receptor, TNF, and NF-κB signaling pathways. Furthermore, NF-κB interacts with PPARγ, blocking PPARγ's activation of its target gene Fabp4, thereby inhibiting adipocyte differentiation. These data bring a signal bridge between immune regulation and adipocyte differentiation. Collectively, our findings indicate that Bmp8a plays a critical role in regulating lipid metabolism and adipogenesis, potentially providing a therapeutic approach for obesity and its comorbidities.

Genes / Markers

Figures

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Expression

Gene	Fish	Conditions	Stage	Anatomy	Assay	Figure
adipoqb	AB	high fat	Adult	adipose tissue	RTPCR	Fig. 2
adipoqb	AB	high fat	Adult	liver	RTPCR	Fig. 2
adipoqb	bmp8a^{ouc1002/ouc1002}	high fat	Adult	adipose tissue	RTPCR	Fig. 2
adipoqb	bmp8a^{ouc1002/ouc1002}	high fat	Adult	liver	RTPCR	Fig. 2
cel.1	AB	high fat	Adult	intestine	ISH	Fig. 2
cel.1	AB	high fat	Adult	liver	ISH	Fig. 2
cel.1	bmp8a^{ouc1002/ouc1002}	high fat	Adult	intestine	ISH	Fig. 2
cel.1	bmp8a^{ouc1002/ouc1002}	high fat	Adult	liver	ISH	Fig. 2
cel.2	AB	high fat	Adult	intestine	ISH	Fig. 2
cel.2	AB	high fat	Adult	liver	ISH	Fig. 2

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Phenotype

Fish	Conditions	Stage	Phenotype	Figure
AB	high fat	Protruding-mouth	liver visceral fat increased amount, abnormal	Fig. 1
AB	high fat	Days 7-13	liver visceral fat increased amount, abnormal	Fig. 1
AB	high fat	Days 21-29	liver visceral fat increased amount, abnormal	Fig. 1
AB	high fat	Days 45-89 to Adult	whole organism increased mass, abnormal	Fig. 1
AB	high fat	Adult	adipose tissue cholesterol increased amount, abnormal	Fig. 1
AB	high fat	Adult	adipose tissue triglyceride increased amount, abnormal	Fig. 1
AB	high fat	Adult	blood cholesterol increased amount, abnormal	Fig. 2
AB	high fat	Adult	blood glucose increased amount, abnormal	Fig. 2
AB	high fat	Adult	blood triglyceride increased amount, abnormal	Fig. 2
AB	high fat	Adult	liver cholesterol increased amount, abnormal	Fig. 1

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Mutations / Transgenics

Allele	Construct	Type	Affected Genomic Region
ouc1002		Small Deletion	bmp8a

Human Disease / Model

Sequence Targeting Reagents

Fish

Fish
AB
bmp8a^{ouc1002/ouc1002}

Antibodies

Name	Type	Antigen Genes	Isotypes	Host Organism
Ab2-ucp1	monoclonal	ucp1	IgG	Rabbit
Ab4-acaca	polyclonal	acaca		Rabbit
Ab5-smad	polyclonal		IgG	Rabbit

Orthology

Engineered Foreign Genes

Mapping

Zhong et al., 2023 ZDB-PUB-230810-57 PMID:37553521

Bmp8a deletion leads to obesity through regulation of lipid metabolism and adipocyte differentiation

Zhong et al., 2023

ZDB-PUB-230810-57
PMID:37553521