Limits...
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.

Show MeSH

Related in: MedlinePlus

cGMP or PKG signaling in brown adipose tissue and skeletal muscle from LF or HF feeding WT or CD47 deficient mice.(A) cGMP levels in brown adipose tissue from LF or HF fed WT mice by direct immunoassay; (B) PKG-I protein levels in brown adipose tissue from LF or HF fed WT mice by immunoblotting (Cropped blots were used); (C) cGMP levels in skeletal muscle from LF or HF fed WT mice by direct immunoassay; (D) PKG-I protein levels in skeletal muscle from LF or HF fed WT mice by immunoblotting (Cropped blots were used). Data are presented as mean ± SE (n = 6 mice/group), *P < 0.05 and **p < 0.01.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4352923&req=5

f9: cGMP or PKG signaling in brown adipose tissue and skeletal muscle from LF or HF feeding WT or CD47 deficient mice.(A) cGMP levels in brown adipose tissue from LF or HF fed WT mice by direct immunoassay; (B) PKG-I protein levels in brown adipose tissue from LF or HF fed WT mice by immunoblotting (Cropped blots were used); (C) cGMP levels in skeletal muscle from LF or HF fed WT mice by direct immunoassay; (D) PKG-I protein levels in skeletal muscle from LF or HF fed WT mice by immunoblotting (Cropped blots were used). Data are presented as mean ± SE (n = 6 mice/group), *P < 0.05 and **p < 0.01.

Mentions: Studies have shown that CD47 activation via TSP1 can disrupt NO/cGMP/PKG signaling in vascular cells233738. Therefore, we determined whether cGMP/PKG signaling in brown adipose tissue (BAT) or skeletal muscle was changed in CD47-/- mice under either LF or HF feeding conditions. As shown in Fig. 9A, under LF feeding conditions, cGMP levels in BAT was increased in CD47-/- mice compared to WT mice. HF diet feeding significantly reduced BAT cGMP levels in WT or in CD47-/- mice compared to their LF controls. There was a trend of increase in BAT cGMP levels in HF-fed CD47-/- mice compared to HF-fed WT mice. For PKG-I protein levels in BAT, under LF feeding conditions, no difference was found between WT and CD47-/- mice. However, under HF feeding conditions, BAT PKG-I protein levels were significantly increased in CD47-/- mice compared to WT mice (Fig. 9B).


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)

cGMP or PKG signaling in brown adipose tissue and skeletal muscle from LF or HF feeding WT or CD47 deficient mice.(A) cGMP levels in brown adipose tissue from LF or HF fed WT mice by direct immunoassay; (B) PKG-I protein levels in brown adipose tissue from LF or HF fed WT mice by immunoblotting (Cropped blots were used); (C) cGMP levels in skeletal muscle from LF or HF fed WT mice by direct immunoassay; (D) PKG-I protein levels in skeletal muscle from LF or HF fed WT mice by immunoblotting (Cropped blots were used). Data are presented as mean ± SE (n = 6 mice/group), *P < 0.05 and **p < 0.01.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f9: cGMP or PKG signaling in brown adipose tissue and skeletal muscle from LF or HF feeding WT or CD47 deficient mice.(A) cGMP levels in brown adipose tissue from LF or HF fed WT mice by direct immunoassay; (B) PKG-I protein levels in brown adipose tissue from LF or HF fed WT mice by immunoblotting (Cropped blots were used); (C) cGMP levels in skeletal muscle from LF or HF fed WT mice by direct immunoassay; (D) PKG-I protein levels in skeletal muscle from LF or HF fed WT mice by immunoblotting (Cropped blots were used). Data are presented as mean ± SE (n = 6 mice/group), *P < 0.05 and **p < 0.01.
Mentions: Studies have shown that CD47 activation via TSP1 can disrupt NO/cGMP/PKG signaling in vascular cells233738. Therefore, we determined whether cGMP/PKG signaling in brown adipose tissue (BAT) or skeletal muscle was changed in CD47-/- mice under either LF or HF feeding conditions. As shown in Fig. 9A, under LF feeding conditions, cGMP levels in BAT was increased in CD47-/- mice compared to WT mice. HF diet feeding significantly reduced BAT cGMP levels in WT or in CD47-/- mice compared to their LF controls. There was a trend of increase in BAT cGMP levels in HF-fed CD47-/- mice compared to HF-fed WT mice. For PKG-I protein levels in BAT, under LF feeding conditions, no difference was found between WT and CD47-/- mice. However, under HF feeding conditions, BAT PKG-I protein levels were significantly increased in CD47-/- mice compared to WT mice (Fig. 9B).

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