CD47 Deficiency Protects Mice From Diet-induced Obesity and Improves Whole Body Glucose Tolerance and Insulin Sensitivity

Maimaitiyiming, Hasiyeti; Norman, Heather; Zhou, Qi Tony; Wang, Shuxia

doi:10.1038/srep08846

Cited by 41 publications

(51 citation statements)

References 55 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Conversely, in mouse models, CD47-deficient mice show decreased weight gain on high-fat diets, increased energy expenditure, improved glucose profile and decreased inflammation26.…”

Section: Resultsmentioning

confidence: 99%

Genome-wide meta-analysis of 241,258 adults accounting for smoking behaviour identifies novel loci for obesity traits

et al. 2017

View full text Add to dashboard Cite

Few genome-wide association studies (GWAS) account for environmental exposures, like smoking, potentially impacting the overall trait variance when investigating the genetic contribution to obesity-related traits. Here, we use GWAS data from 51,080 current smokers and 190,178 nonsmokers (87% European descent) to identify loci influencing BMI and central adiposity, measured as waist circumference and waist-to-hip ratio both adjusted for BMI. We identify 23 novel genetic loci, and 9 loci with convincing evidence of gene-smoking interaction (GxSMK) on obesity-related traits. We show consistent direction of effect for all identified loci and significance for 18 novel and for 5 interaction loci in an independent study sample. These loci highlight novel biological functions, including response to oxidative stress, addictive behaviour, and regulatory functions emphasizing the importance of accounting for environment in genetic analyses. Our results suggest that tobacco smoking may alter the genetic susceptibility to overall adiposity and body fat distribution.

show abstract

“…Conversely, in mouse models, CD47-deficient mice show decreased weight gain on high-fat diets, increased energy expenditure, improved glucose profile and decreased inflammation26.…”

Section: Resultsmentioning

confidence: 99%

Genome-wide meta-analysis of 241,258 adults accounting for smoking behaviour identifies novel loci for obesity traits

et al. 2017

View full text Add to dashboard Cite

show abstract

“…No genome-wide significant associations have been reported for the lead SNP or other SNPs in the CD47 gene before232425. However, a recent study revealed a link to diet-induced obesity in mice and suggests CD47 as a potential drug-target to combat obesity and metabolic complications2627.…”

Section: Resultsmentioning

confidence: 99%

A principal component meta-analysis on multiple anthropometric traits identifies novel loci for body shape

et al. 2016

View full text Add to dashboard Cite

Large consortia have revealed hundreds of genetic loci associated with anthropometric traits, one trait at a time. We examined whether genetic variants affect body shape as a composite phenotype that is represented by a combination of anthropometric traits. We developed an approach that calculates averaged PCs (AvPCs) representing body shape derived from six anthropometric traits (body mass index, height, weight, waist and hip circumference, waist-to-hip ratio). The first four AvPCs explain >99% of the variability, are heritable, and associate with cardiometabolic outcomes. We performed genome-wide association analyses for each body shape composite phenotype across 65 studies and meta-analysed summary statistics. We identify six novel loci: LEMD2 and CD47 for AvPC1, RPS6KA5/C14orf159 and GANAB for AvPC3, and ARL15 and ANP32 for AvPC4. Our findings highlight the value of using multiple traits to define complex phenotypes for discovery, which are not captured by single-trait analyses, and may shed light onto new pathways.

show abstract

“…Genomic DNA was extracted from subcutaneous white adipose tissue (WAT) by the DNAeasy Blood and Tissue kit (Qiagen, Germantown, MD, http://www.qiagen.com). QPCR was performed on COX1 mitochondrial DNA and normalized to a nuclear 28S sequence . The sequences of primer sets used in this study are listed in Supporting Information Table 1.…”

Section: Methodsmentioning

confidence: 99%

“…Germantown, MD, http://www.qiagen.com). QPCR was performed on COX1 mitochondrial DNA and normalized to a nuclear 28S sequence [28,29]. The sequences of primer sets used in this study are listed in Supporting Information Table 1.…”

Section: Stem Cellsmentioning

confidence: 99%

Targeting IκB kinase β in Adipocyte Lineage Cells for Treatment of Obesity and Metabolic Dysfunctions

et al. 2016

View full text Add to dashboard Cite

IκB kinase β (IKKβ), a central coordinator of inflammation through activation of NF-κB, has been identified as a potential therapeutic target for the treatment of obesity-associated metabolic dysfunctions. In this study, we evaluated an antisense oligonucleotide (ASO) inhibitor of IKKβ and found that IKKβ ASO ameliorated diet-induced metabolic dysfunctions in mice. Interestingly, IKKβ ASO also inhibited adipocyte differentiation and reduced adiposity in high-fat (HF)-fed mice, indicating an important role of IKKβ signaling in the regulation of adipocyte differentiation. Indeed, CRISPR/Cas9-mediated genomic deletion of IKKβ in 3T3-L1 preadipocytes blocked these cells differentiating into adipocytes. To further elucidate the role of adipose progenitor IKKβ signaling in diet-induced obesity, we generated mice that selectively lack IKKβ in the white adipose lineage and confirmed the essential role of IKKβ in mediating adipocyte differentiation in vivo. Deficiency of IKKβ decreased HF-elicited adipogenesis in addition to reducing inflammation and protected mice from diet-induced obesity and insulin resistance. Further, pharmacological inhibition of IKKβ also blocked human adipose stem cell differentiation. Our findings establish IKKβ as a pivotal regulator of adipogenesis and suggest that overnutrition-mediated IKKβ activation serves as an initial signal that triggers adipose progenitor cell differentiation in response to HF feeding. Inhibition of IKKβ with antisense therapy may represent as a novel therapeutic approach to combat obesity and metabolic dysfunctions.

show abstract

CD47 Deficiency Protects Mice From Diet-induced Obesity and Improves Whole Body Glucose Tolerance and Insulin Sensitivity

Cited by 41 publications

References 55 publications

Genome-wide meta-analysis of 241,258 adults accounting for smoking behaviour identifies novel loci for obesity traits

Genome-wide meta-analysis of 241,258 adults accounting for smoking behaviour identifies novel loci for obesity traits

A principal component meta-analysis on multiple anthropometric traits identifies novel loci for body shape

Targeting IκB kinase β in Adipocyte Lineage Cells for Treatment of Obesity and Metabolic Dysfunctions

Contact Info

Product

Resources

About