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CD47 deficiency protects mice from diet-induced obesity and improves whole body glucose tolerance and insulin sensitivity.

Maimaitiyiming H, Norman H, Zhou Q, Wang S - Sci Rep (2015)

Bottom Line: CD47 is a transmembrane protein with several functions including self-recognition, immune cell communication, and cell signaling.This led to decreased MCP1/CCR2 dependent macrophage infiltration into adipose tissue and reduced inflammation, resulting in improved glucose tolerance and insulin sensitivity.In addition, CD47 deficiency stimulated the expression of UCP1 and carnitine palmitoyltransferase 1b (CPT1b) levels in brown adipose tissue, leading to increased lipid utilization and heat production.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacology and Nutritional Sciences, University of Kentucky, Lexington, KY 40536; Lexington Veterans Affairs Medical Center, Lexington, KY.

ABSTRACT
CD47 is a transmembrane protein with several functions including self-recognition, immune cell communication, and cell signaling. Although it has been extensively studied in cancer and ischemia, CD47 function in obesity has never been explored. In this study, we utilized CD47 deficient mice in a high-fat diet induced obesity model to study for the first time whether CD47 plays a role in the development of obesity and metabolic complications. Male CD47 deficient and wild type (WT) control mice were fed with either low fat (LF) or high fat (HF) diets for 16 weeks. Interestingly, we found that CD47 deficient mice were protected from HF diet-induced obesity displaying decreased weight gain and reduced adiposity. This led to decreased MCP1/CCR2 dependent macrophage infiltration into adipose tissue and reduced inflammation, resulting in improved glucose tolerance and insulin sensitivity. In addition, CD47 deficiency stimulated the expression of UCP1 and carnitine palmitoyltransferase 1b (CPT1b) levels in brown adipose tissue, leading to increased lipid utilization and heat production. This contributes to the increased energy utilization and reduced adiposity observed in these mice. Taken together, these data revealed a novel role for CD47 in the development of obesity and its related metabolic complications.

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Related in: MedlinePlus

Metabolic gene expression in skeletal muscle from LF or HF feeding WT or CD47 deficient mice.(A) Mitochondria DNA copy number in skeletal mice from four groups of mice and (B) expression of metabolic genes including acylcoA Oxidase (ACO), Fatty acid transporter protein (FATP1), Carnitine palmitoyltransferase 1b (CPT1b), UCP3, PGC-1α, COX I, COX III and ATPsyn by real-time PCR. Data are presented as mean ± SE (n = 6–7 mice/group), *P < 0.05.
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f7: Metabolic gene expression in skeletal muscle from LF or HF feeding WT or CD47 deficient mice.(A) Mitochondria DNA copy number in skeletal mice from four groups of mice and (B) expression of metabolic genes including acylcoA Oxidase (ACO), Fatty acid transporter protein (FATP1), Carnitine palmitoyltransferase 1b (CPT1b), UCP3, PGC-1α, COX I, COX III and ATPsyn by real-time PCR. Data are presented as mean ± SE (n = 6–7 mice/group), *P < 0.05.

Mentions: To further determine the mechanism of increased energy utilization in HF-Fed CD47 deficient mice, first, we analyzed the expression of multiple genes in skeletal muscle that relate to mitochondria function and fuel utilization. The rationale for this analysis was based on the previous report showing that skeletal muscle from CD47 deficient mice had greater number of mitochondria and improved function32, which suggested a possible contribution of skeletal muscle to the metabolic phenotype observed in the current study. Therefore, mitochondria DNA copy number and expression of a series genes relating to mitochondria oxidative function and fatty acid catabolism were analyzed. The results showed that mitochondria DNA copy number was significantly increased in CD47 deficient mice compared to WT mice under either LF or HF feeding conditions (Fig. 7A). However, expression levels of genes relating to mitochondria oxidative function and fatty acid catabolism were comparable in CD47 deficient mice compared to WT mice under either LF or HF feeding conditions (Fig. 7B), suggesting that skeletal muscle functional change might be not the major contribution to the increased energy utilization phenotype in HF-fed CD47 deficient mice.


CD47 deficiency protects mice from diet-induced obesity and improves whole body glucose tolerance and insulin sensitivity.

Maimaitiyiming H, Norman H, Zhou Q, Wang S - Sci Rep (2015)

Metabolic gene expression in skeletal muscle from LF or HF feeding WT or CD47 deficient mice.(A) Mitochondria DNA copy number in skeletal mice from four groups of mice and (B) expression of metabolic genes including acylcoA Oxidase (ACO), Fatty acid transporter protein (FATP1), Carnitine palmitoyltransferase 1b (CPT1b), UCP3, PGC-1α, COX I, COX III and ATPsyn by real-time PCR. Data are presented as mean ± SE (n = 6–7 mice/group), *P < 0.05.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4352923&req=5

f7: Metabolic gene expression in skeletal muscle from LF or HF feeding WT or CD47 deficient mice.(A) Mitochondria DNA copy number in skeletal mice from four groups of mice and (B) expression of metabolic genes including acylcoA Oxidase (ACO), Fatty acid transporter protein (FATP1), Carnitine palmitoyltransferase 1b (CPT1b), UCP3, PGC-1α, COX I, COX III and ATPsyn by real-time PCR. Data are presented as mean ± SE (n = 6–7 mice/group), *P < 0.05.
Mentions: To further determine the mechanism of increased energy utilization in HF-Fed CD47 deficient mice, first, we analyzed the expression of multiple genes in skeletal muscle that relate to mitochondria function and fuel utilization. The rationale for this analysis was based on the previous report showing that skeletal muscle from CD47 deficient mice had greater number of mitochondria and improved function32, which suggested a possible contribution of skeletal muscle to the metabolic phenotype observed in the current study. Therefore, mitochondria DNA copy number and expression of a series genes relating to mitochondria oxidative function and fatty acid catabolism were analyzed. The results showed that mitochondria DNA copy number was significantly increased in CD47 deficient mice compared to WT mice under either LF or HF feeding conditions (Fig. 7A). However, expression levels of genes relating to mitochondria oxidative function and fatty acid catabolism were comparable in CD47 deficient mice compared to WT mice under either LF or HF feeding conditions (Fig. 7B), suggesting that skeletal muscle functional change might be not the major contribution to the increased energy utilization phenotype in HF-fed CD47 deficient mice.

Bottom Line: CD47 is a transmembrane protein with several functions including self-recognition, immune cell communication, and cell signaling.This led to decreased MCP1/CCR2 dependent macrophage infiltration into adipose tissue and reduced inflammation, resulting in improved glucose tolerance and insulin sensitivity.In addition, CD47 deficiency stimulated the expression of UCP1 and carnitine palmitoyltransferase 1b (CPT1b) levels in brown adipose tissue, leading to increased lipid utilization and heat production.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacology and Nutritional Sciences, University of Kentucky, Lexington, KY 40536; Lexington Veterans Affairs Medical Center, Lexington, KY.

ABSTRACT
CD47 is a transmembrane protein with several functions including self-recognition, immune cell communication, and cell signaling. Although it has been extensively studied in cancer and ischemia, CD47 function in obesity has never been explored. In this study, we utilized CD47 deficient mice in a high-fat diet induced obesity model to study for the first time whether CD47 plays a role in the development of obesity and metabolic complications. Male CD47 deficient and wild type (WT) control mice were fed with either low fat (LF) or high fat (HF) diets for 16 weeks. Interestingly, we found that CD47 deficient mice were protected from HF diet-induced obesity displaying decreased weight gain and reduced adiposity. This led to decreased MCP1/CCR2 dependent macrophage infiltration into adipose tissue and reduced inflammation, resulting in improved glucose tolerance and insulin sensitivity. In addition, CD47 deficiency stimulated the expression of UCP1 and carnitine palmitoyltransferase 1b (CPT1b) levels in brown adipose tissue, leading to increased lipid utilization and heat production. This contributes to the increased energy utilization and reduced adiposity observed in these mice. Taken together, these data revealed a novel role for CD47 in the development of obesity and its related metabolic complications.

Show MeSH
Related in: MedlinePlus