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Erythropoietin signaling: a novel regulator of white adipose tissue inflammation during diet-induced obesity.

Alnaeeli M, Raaka BM, Gavrilova O, Teng R, Chanturiya T, Noguchi CT - Diabetes (2014)

Bottom Line: Using comprehensive in vivo and in vitro analyses in mice, EPO treatment inhibited WAT inflammation, normalized insulin sensitivity, and reduced glucose intolerance.Remarkably, and prior to any detectable changes in body weight or composition, EPO treatment reduced M1-like Mф and increased M2-like Mф in WAT, while decreasing inflammatory monocytes.These anti-inflammatory effects were found to be driven, at least in part, by direct EPO-R response in Mф via Stat3 activation, where EPO effects on M2 but not M1 Mф required interleukin-4 receptor/Stat6.

View Article: PubMed Central - PubMed

Affiliation: Molecular Medicine Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD.

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Endogenous EPO/EPO-R signaling and glucose metabolism during DIO. A: For ITT, glucose levels were measured after intraperitoneal injection of 1 unit/kg insulin. B: For GTT, glucose levels were measured after intraperitoneal injection of 1 g/kg glucose. Fasting glucose (C) and serum insulin (D) levels were determined. ∆EpoR mice with DIO, induced by 12 weeks of HFD feeding, were injected subcutaneously with saline or EPO (1,000 units/kg) every 48 h for the final 2 weeks of HFD feeding, and hematocrit (E), ITT (F), GTT (G), and flow cytometry analysis of perigonadal fat SVF cells (H) were determined. All measurements were performed at the end of week 12. Data presented as mean ± SEM for n = 8 mice per group, representative of three independent experiments with similar results. *P < 0.05.
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Figure 8: Endogenous EPO/EPO-R signaling and glucose metabolism during DIO. A: For ITT, glucose levels were measured after intraperitoneal injection of 1 unit/kg insulin. B: For GTT, glucose levels were measured after intraperitoneal injection of 1 g/kg glucose. Fasting glucose (C) and serum insulin (D) levels were determined. ∆EpoR mice with DIO, induced by 12 weeks of HFD feeding, were injected subcutaneously with saline or EPO (1,000 units/kg) every 48 h for the final 2 weeks of HFD feeding, and hematocrit (E), ITT (F), GTT (G), and flow cytometry analysis of perigonadal fat SVF cells (H) were determined. All measurements were performed at the end of week 12. Data presented as mean ± SEM for n = 8 mice per group, representative of three independent experiments with similar results. *P < 0.05.

Mentions: To investigate the role of endogenous EPO/EPO-R signaling in regulating glucose metabolism, we compared WT with ∆EpoR mice after 12 weeks of HFD feeding. ∆EpoR mice showed higher insulin resistance, glucose intolerance, fasting blood glucose, and serum insulin (Fig. 8A–D). ∆EpoR mice maintained high insulin resistance after 2 weeks of EPO administration (Fig. 8E and F), and there was no change in the area under the curve and no significant difference in glucose intolerance after EPO treatment (Fig. 8G). Not surprisingly, Mф infiltration and subtype composition in WAT of ∆EpoR mice remained similar after EPO administration (Fig. 8H).


Erythropoietin signaling: a novel regulator of white adipose tissue inflammation during diet-induced obesity.

Alnaeeli M, Raaka BM, Gavrilova O, Teng R, Chanturiya T, Noguchi CT - Diabetes (2014)

Endogenous EPO/EPO-R signaling and glucose metabolism during DIO. A: For ITT, glucose levels were measured after intraperitoneal injection of 1 unit/kg insulin. B: For GTT, glucose levels were measured after intraperitoneal injection of 1 g/kg glucose. Fasting glucose (C) and serum insulin (D) levels were determined. ∆EpoR mice with DIO, induced by 12 weeks of HFD feeding, were injected subcutaneously with saline or EPO (1,000 units/kg) every 48 h for the final 2 weeks of HFD feeding, and hematocrit (E), ITT (F), GTT (G), and flow cytometry analysis of perigonadal fat SVF cells (H) were determined. All measurements were performed at the end of week 12. Data presented as mean ± SEM for n = 8 mice per group, representative of three independent experiments with similar results. *P < 0.05.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

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Figure 8: Endogenous EPO/EPO-R signaling and glucose metabolism during DIO. A: For ITT, glucose levels were measured after intraperitoneal injection of 1 unit/kg insulin. B: For GTT, glucose levels were measured after intraperitoneal injection of 1 g/kg glucose. Fasting glucose (C) and serum insulin (D) levels were determined. ∆EpoR mice with DIO, induced by 12 weeks of HFD feeding, were injected subcutaneously with saline or EPO (1,000 units/kg) every 48 h for the final 2 weeks of HFD feeding, and hematocrit (E), ITT (F), GTT (G), and flow cytometry analysis of perigonadal fat SVF cells (H) were determined. All measurements were performed at the end of week 12. Data presented as mean ± SEM for n = 8 mice per group, representative of three independent experiments with similar results. *P < 0.05.
Mentions: To investigate the role of endogenous EPO/EPO-R signaling in regulating glucose metabolism, we compared WT with ∆EpoR mice after 12 weeks of HFD feeding. ∆EpoR mice showed higher insulin resistance, glucose intolerance, fasting blood glucose, and serum insulin (Fig. 8A–D). ∆EpoR mice maintained high insulin resistance after 2 weeks of EPO administration (Fig. 8E and F), and there was no change in the area under the curve and no significant difference in glucose intolerance after EPO treatment (Fig. 8G). Not surprisingly, Mф infiltration and subtype composition in WAT of ∆EpoR mice remained similar after EPO administration (Fig. 8H).

Bottom Line: Using comprehensive in vivo and in vitro analyses in mice, EPO treatment inhibited WAT inflammation, normalized insulin sensitivity, and reduced glucose intolerance.Remarkably, and prior to any detectable changes in body weight or composition, EPO treatment reduced M1-like Mф and increased M2-like Mф in WAT, while decreasing inflammatory monocytes.These anti-inflammatory effects were found to be driven, at least in part, by direct EPO-R response in Mф via Stat3 activation, where EPO effects on M2 but not M1 Mф required interleukin-4 receptor/Stat6.

View Article: PubMed Central - PubMed

Affiliation: Molecular Medicine Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD.

Show MeSH
Related in: MedlinePlus