Gab2 deficiency suppresses high-fat diet-induced obesity by reducing adipose tissue inflammation and increasing brown adipose function in mice
Open Access
- 26 February 2021
- journal article
- research article
- Published by Springer Science and Business Media LLC in Cell Death & Disease
- Vol. 12 (2), 1-14
- https://doi.org/10.1038/s41419-021-03519-9
Abstract
Obesity is caused by a long-term imbalance between energy intake and consumption and is regulated by multiple signals. This study investigated the effect of signaling scaffolding protein Gab2 on obesity and its relevant regulation mechanism. Gab2 knockout (KO) and wild-type (WT) mice were fed with a standard diet (SD) or high-fat diet (HFD) for 12 weeks. The results showed that the a high-fat diet-induced Gab2 expression in adipose tissues, but deletion of Gab2 attenuated weight gain and improved glucose tolerance in mice fed with a high-fat diet. White adipose tissue and systemic inflammations were reduced in HFD-fed Gab2 deficiency mice. Gab2 deficiency increased the expression of Ucp1 and other thermogenic genes in brown adipose tissue. Furthermore, the regulation of Gab2 on the mature differentiation and function of adipocytes was investigated in vitro using primary or immortalized brown preadipocytes. The expression of brown fat-selective genes was found to be elevated in differentiated adipocytes without Gab2. The mechanism of Gab2 regulating Ucp1 expression in brown adipocytes involved with its downstream PI3K (p85)-Akt-FoxO1 signaling pathway. Our research suggests that deletion of Gab2 suppresses diet-induced obesity by multiple pathways and Gab2 may be a novel therapeutic target for the treatment of obesity and associated complications.Keywords
Funding Information
- National Natural Science Foundation of China (31970797, 31671564)
This publication has 61 references indexed in Scilit:
- Adiponectin, driver or passenger on the road to insulin sensitivity?Molecular Metabolism, 2013
- The adipose organ of obesity-prone C57BL/6J mice is composed of mixed white and brown adipocytesJournal of Lipid Research, 2012
- Gab2 Promotes Colony-Stimulating Factor 1-Regulated Macrophage Expansion via Alternate Effectors at Different Stages of DevelopmentMolecular and Cellular Biology, 2011
- Adipokines in inflammation and metabolic diseaseNature Reviews Immunology, 2011
- Adipose tissue macrophages in insulin-resistant subjects are associated with collagen VI and fibrosis and demonstrate alternative activationAmerican Journal of Physiology-Endocrinology and Metabolism, 2010
- Adiponectin Promotes Macrophage Polarization toward an Anti-inflammatory PhenotypeOnline Journal of Public Health Informatics, 2010
- Function, regulation and pathological roles of the Gab/DOS docking proteinsCell Communication and Signaling, 2009
- Gab family proteins are essential for postnatal maintenance of cardiac function via neuregulin-1/ErbB signalingJCI Insight, 2007
- T-Cell Protein Tyrosine Phosphatase (Tcptp) Is a Negative Regulator of Colony-Stimulating Factor 1 Signaling and Macrophage DifferentiationMolecular and Cellular Biology, 2006
- Indispensable role of mitochondrial UCP1 for antiobesity effect of β3-adrenergic stimulationAmerican Journal of Physiology-Endocrinology and Metabolism, 2006