Mice with Fabp4-Cre ablation of Arid5b are resistant to diet-induced obesity and hepatic steatosis

Whitson, Robert H.; Li, Shulian; Zhang, Guoxiang; Larson, Garrett P.; Itakura, Keiichi

doi:10.1016/j.mce.2021.111246

Cited by 9 publications

(7 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…ARID5B is known to transcriptionally activate or repress metabolic gene expression 65 involved in adipogenesis and lipid metabolism 66 and mesenchymal cell differentiation during SMC phenotypic modulation 67 . ARID5B is expressed in ACTA2 + SMCs and in endothelial cells marked by endothelial-to-mesenchymal transition 45 , and epigenome-based fine-mapping identified ARID5B as a target gene in coronary and aortic tissue.…”

Section: Discussionmentioning

confidence: 99%

Multi-ancestry genome-wide study identifies effector genes and druggable pathways for coronary artery calcification

Kavousi,

Bos,

Barnes

et al. 2023

Nat Genet

View full text Add to dashboard Cite

show abstract

Section: Discussionmentioning

confidence: 99%

Multi-ancestry genome-wide study identifies effector genes and druggable pathways for coronary artery calcification

Kavousi,

Bos,

Barnes

et al. 2023

Nat Genet

View full text Add to dashboard Cite

show abstract

“…Fatty acid-binding protein 4 (FABP4), a member of fatty acid-binding proteins (FABPs) family, is predominantly expressed in macrophages and adipocytes; it plays a critical role in lipid metabolism and inflammatory processes 3 . Previous studies have shown that circulating FABP4 may be a useful additional biomarker to evaluate patients with stable peripheral vascular diseases at risk of major cardiovascular complications 4 .…”

Section: Introductionmentioning

confidence: 99%

FABP4 activates the JAK2/STAT2 pathway via Rap1a in the homocysteine-induced macrophage inflammatory response in ApoE mice atherosclerosis

Zhang

Wang

et al. 2022

Laboratory Investigation

View full text Add to dashboard Cite

Atherosclerosis is a chronic inflammatory vascular disease, and inflammation plays a critical role in its formation and progression. Elevated serum homocysteine (Hcy) is an independent risk factor for atherosclerosis. Previous studies have shown that fatty acid binding protein 4 (FABP4) plays an important role in macrophage inflammation and lipid metabolism in atherosclerosis induced by Hcy. However, the underlying molecular mechanism of FABP4 in Hcy-induced macrophage inflammation remains unknown. In this study, we found that FABP4 activated the Janus kinase 2/signal transducer and activator of transcription 2 (JAK2/STAT2) pathway in macrophage inflammation induced by Hcy. Of note, we further observed that ras-related protein Rap-1a (Rap1a) induced the Tyr416 phosphorylation and membrane translocation of non-receptor tyrosine kinase (c-Src) to activate the JAK2/STAT2 pathway. In addition, the suppressor of cytokine signaling 1 (SOCS1)—a transcriptional target of signal transducer and activator of transcription (STATs) inhibited the JAK2/STAT2 pathway and Rap1a expression via a negative feedback loop. In summary, these results demonstrated that FABP4 promotes c-Src phosphorylation and membrane translocation via Rap1a to activate the JAK2/STAT2 pathway, contributing to Hcy-accelerated macrophage inflammation in ApoE−/− mice.

show abstract

“…(6) Diverse genetic backgrounds are factors. Fabp4-deficient mice showed resistance to obesity and fatty liver[ 10 ]. (7) Activity of the nervous system is inconsistent among individuals.…”

Section: Introductionmentioning

confidence: 99%

Potential novel biomarkers in small intestine for obesity/obesity resistance revealed by multi-omics analysis

Pang

Zheng

et al. 2022

Lipids Health Dis

View full text Add to dashboard Cite

Background Although obesity is caused by different factors, individual susceptibility to obesity differs among people under the same circumstances. The microbiota in the caecum or fresh faeces and metabolites in blood or urine contribute to obesity resistance; however, the microbiota or metabolites in the small intestine have not been extensively studied. Methods To investigate the relationship between the microbiota or metabolites in the small intestine and susceptibility to obesity, eighty-eight male C57BL/6 mice were fed a high-fat diet (HFD) for 8 weeks to establish two models of obesity and obesity resistance. For further study, six mice were chosen from among the obesity models, and twelve mice were randomly chosen from among the obesity resistance models. After fasting plasma glucose and behavioural testing, the mice were fed in single cages for another 4 weeks to observe their weight and food intake. All mice were sacrificed at 20 weeks of age. Serum ALT, AST, HDL, LDL, TG and TC levels were measured using an automatic biochemical analyser. The microbiota and metabolites in the small intestine contents were analysed using 16 S sequencing and an ultrahigh-performance liquid chromatographic system, respectively. Transcripts in the jejunum were evaluated using full-length transcriptome sequencing and verified by qPCR. Results The results showed that HFD induced depression and anxiety behaviours and higher fasting plasma glucose, ALT, AST, HDL, LDL, TG and TC levels in the obese mice; however, these levels were improved in obese resistance mice. The correlation analysis showed that the phosphatidylcholine, TG, and phosphatidylethanolamine levels were higher in obese mice and correlated positively with intestinal microflora (Desulfovibrio and Gemella) and the Cxcl10 gene. A higher abundance of Clostridium_sensu_stricto_1 in obesity-resistant mice correlated negatively with the metabolite contents (neuromedin N and enkephalin L) and Pck1 gene expression and correlated positively with certain metabolites (5-hydroxy-L-tryptophan, cinnamyl alcohol and 1 H-indole-3-acetamide) and genes expression (Gdf15, Igfbp6 and Spp1). Conclusion Clostridium_sensu_stricto_1, neuromedin N, enkephalin L, Pck1, 5-hydroxy-L-tryptophan, Cxcl10 and cinnamyl alcohol may be novel biomarkers in the small intestine for obesity/obesity resistance. These might be helpful for obesity prevention or for treating obese patients.

show abstract

Mice with Fabp4-Cre ablation of Arid5b are resistant to diet-induced obesity and hepatic steatosis

Cited by 9 publications

References 36 publications

Multi-ancestry genome-wide study identifies effector genes and druggable pathways for coronary artery calcification

Multi-ancestry genome-wide study identifies effector genes and druggable pathways for coronary artery calcification

FABP4 activates the JAK2/STAT2 pathway via Rap1a in the homocysteine-induced macrophage inflammatory response in ApoE mice atherosclerosis

Potential novel biomarkers in small intestine for obesity/obesity resistance revealed by multi-omics analysis

Contact Info

Product

Resources

About