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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

CD47 deficient mice were protected from high fat diet-induced obesity.Eight week old male CD47 deficient mice and wild type C57BL6 controls were fed with low fat (LF) or high fat (HF) diet for 16 weeks. Weekly body weight (A) and body weight gain (B) were shown. Fat (C) and lean mass (D) of mice were measured by EchoMRI. (E) Absolute weight of white and brown adipose tissues was measured immediately following sacrifice. Data are presented as mean ± SE (n = 7 mice/group), *p < 0.05, **p < 0.01. EAT: epididymal adipose tissue; MAT: mesenteric adipose tissue; PAT: perirenal adipose tissue; SAT: subcutaneous adipose tissue; BAT: brown adipose tissue.
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f1: CD47 deficient mice were protected from high fat diet-induced obesity.Eight week old male CD47 deficient mice and wild type C57BL6 controls were fed with low fat (LF) or high fat (HF) diet for 16 weeks. Weekly body weight (A) and body weight gain (B) were shown. Fat (C) and lean mass (D) of mice were measured by EchoMRI. (E) Absolute weight of white and brown adipose tissues was measured immediately following sacrifice. Data are presented as mean ± SE (n = 7 mice/group), *p < 0.05, **p < 0.01. EAT: epididymal adipose tissue; MAT: mesenteric adipose tissue; PAT: perirenal adipose tissue; SAT: subcutaneous adipose tissue; BAT: brown adipose tissue.

Mentions: To assess the metabolic role of CD47 in mice, CD47 deficient mice and WT controls were challenged with either a low fat (LF, 10% kcal from fat) or high fat (HF, 60% kcal from fat) diet for 16 weeks. Under LF diet, although CD 47 deficient mice had a trend of decrease in body weight as compared to WT mice, no significant changes were observed throughout the study (Fig. 1A). When challenged with HF diet, CD47 deficient mice exhibited significantly reduced body weight starting from 7 weeks' feeding till the end of the study. These mice gained less weight than HF-fed WT mice (Fig. 1B). At the end of study, body composition was determined in mice by using EchoMRI. There was significantly reduced fat mass in HF-fed CD47 deficient mice as compared to HF-fed WT mice (Fig. 1C), which was in agreement with the absolute weight of different adipose tissue depots (Fig. 1E). Lean mass was comparable in HF-fed CD47 deficient mice and WT mice (Fig. 1D). Consistent with the decreased adiposity, HF-fed CD47 deficient mice had reduced leptin levels (ng/ml, WT HF: 14.4 ± 4.89 vs. CD47-/- HF: 6.83 ± 1.09, p < 0.05). Moreover, plasma total cholesterol (TC) and free fatty acid (FFA) levels were significantly reduced in HF-fed CD47 deficient mice (TC (mg/dl), WT HF: 115.08 ± 7.25 vs. CD47-/- HF: 80.04 ± 7.87, p < 0.01; FFA (mEq/L), WT HF: 0.34 ± 0.01 vs. CD47-/- HF: 0.28 ± 0.02, p < 0.05). Together, these data suggests that CD47 deficiency protects mice from diet-induced obesity.


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)

CD47 deficient mice were protected from high fat diet-induced obesity.Eight week old male CD47 deficient mice and wild type C57BL6 controls were fed with low fat (LF) or high fat (HF) diet for 16 weeks. Weekly body weight (A) and body weight gain (B) were shown. Fat (C) and lean mass (D) of mice were measured by EchoMRI. (E) Absolute weight of white and brown adipose tissues was measured immediately following sacrifice. Data are presented as mean ± SE (n = 7 mice/group), *p < 0.05, **p < 0.01. EAT: epididymal adipose tissue; MAT: mesenteric adipose tissue; PAT: perirenal adipose tissue; SAT: subcutaneous adipose tissue; BAT: brown adipose tissue.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f1: CD47 deficient mice were protected from high fat diet-induced obesity.Eight week old male CD47 deficient mice and wild type C57BL6 controls were fed with low fat (LF) or high fat (HF) diet for 16 weeks. Weekly body weight (A) and body weight gain (B) were shown. Fat (C) and lean mass (D) of mice were measured by EchoMRI. (E) Absolute weight of white and brown adipose tissues was measured immediately following sacrifice. Data are presented as mean ± SE (n = 7 mice/group), *p < 0.05, **p < 0.01. EAT: epididymal adipose tissue; MAT: mesenteric adipose tissue; PAT: perirenal adipose tissue; SAT: subcutaneous adipose tissue; BAT: brown adipose tissue.
Mentions: To assess the metabolic role of CD47 in mice, CD47 deficient mice and WT controls were challenged with either a low fat (LF, 10% kcal from fat) or high fat (HF, 60% kcal from fat) diet for 16 weeks. Under LF diet, although CD 47 deficient mice had a trend of decrease in body weight as compared to WT mice, no significant changes were observed throughout the study (Fig. 1A). When challenged with HF diet, CD47 deficient mice exhibited significantly reduced body weight starting from 7 weeks' feeding till the end of the study. These mice gained less weight than HF-fed WT mice (Fig. 1B). At the end of study, body composition was determined in mice by using EchoMRI. There was significantly reduced fat mass in HF-fed CD47 deficient mice as compared to HF-fed WT mice (Fig. 1C), which was in agreement with the absolute weight of different adipose tissue depots (Fig. 1E). Lean mass was comparable in HF-fed CD47 deficient mice and WT mice (Fig. 1D). Consistent with the decreased adiposity, HF-fed CD47 deficient mice had reduced leptin levels (ng/ml, WT HF: 14.4 ± 4.89 vs. CD47-/- HF: 6.83 ± 1.09, p < 0.05). Moreover, plasma total cholesterol (TC) and free fatty acid (FFA) levels were significantly reduced in HF-fed CD47 deficient mice (TC (mg/dl), WT HF: 115.08 ± 7.25 vs. CD47-/- HF: 80.04 ± 7.87, p < 0.01; FFA (mEq/L), WT HF: 0.34 ± 0.01 vs. CD47-/- HF: 0.28 ± 0.02, p < 0.05). Together, these data suggests that CD47 deficiency protects mice from diet-induced obesity.

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