Chronic Intermittent Hypoxia Contributes To Pro-Inflammatory Macrophage Alteration In Visceral Adipose Tissue Of Lean And Obese Mice

Aoife M Murphy, Amandine Thomas, Murtaza Tambuwala, Walter T McNicholas, Helen M Roche, Cormac T Taylor, Jean-Louis Pepin, Claire Arnaud, Silke Ryan

Research output: Contribution to journalArticle

Abstract

Introduction: Intermittent hypoxia (IH) as a hallmark feature of obstructive sleep apnea (OSA) is a major pathophysiological trigger for cardiovascular and metabolic diseases occurring in OSA. Obesity and OSA may interact in cardiometabolic processes and IH has been suggested to mediate its action through the visceral adipose tissue (AT) promoting a pro-inflammatory response. Metabolically dysfunctional AT in obesity is characterized by macrophage infiltration and polarization of macrophages towards a pro-inflammatory insulin resistance promoting M1, “classically activated” over an anti M2, “alternatively activated” phenotype. Aim of the study was to investigate the impact of IH on AT M1/M2 relationship in lean and diet-induced obese (DIO) mice. Methods: Male C57Bl/6 mice (5-weeks old) were fed on a low-fat diet (LF, 10%fat, n=20) or on a high-fat diet (HF, 60% fat, n=26) for 14 weeks and then randomized to 6 weeks of IH (inspired oxygen 5-21%, 60 sec cycle, 8hrs/day) or intermittent normoxia (N). Insulin tolerance test (ITT) was performed at the end of the protocol. M1 and M2 populations of the stromal vascular fraction of epididymal AT were assessed by flow cytometry.Results: As expected, HF-IH mice were significantly lighter than HF-N at the end of the study, but there was no difference in weight between LF-IH and LF-N. IH contributed to insulin resistance in both, LF and HF and this was associated with higher percentage of AT M1 macrophages (LF: N vs IH: 1.5±0.4% vs 4.3±3.7; p=0.049; HF: 6.8±2.8 vs 11.8±3.8; p=0.009). HF mice demonstrated lower M2 than LF mice (p=0.022) but there was no difference between groups on IH and N treatment.Conclusion: IH contributes to pro-inflammatory macrophage polarization in AT and insulin resistance. Further studies will determine the intermediate mechanisms underlying these events.
LanguageEnglish
Pages2691-2691
JournalAmerican Journal of Respiratory and Critical Care Medicine
VolumeB30
Publication statusPublished - 18 May 2015

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Obese Mice
Intra-Abdominal Fat
Macrophages
Adipose Tissue
Obstructive Sleep Apnea
Insulin Resistance
Obesity
Fats
Hypoxia
Fat-Restricted Diet
Metabolic Diseases
High Fat Diet
Blood Vessels
Flow Cytometry
Cardiovascular Diseases
Insulin
Oxygen
Diet
Phenotype
Weights and Measures

Keywords

  • Hypoxia
  • inflammation
  • mice

Cite this

Murphy, Aoife M ; Thomas, Amandine ; Tambuwala, Murtaza ; McNicholas, Walter T ; Roche, Helen M ; Taylor, Cormac T ; Pepin, Jean-Louis ; Arnaud, Claire ; Ryan, Silke. / Chronic Intermittent Hypoxia Contributes To Pro-Inflammatory Macrophage Alteration In Visceral Adipose Tissue Of Lean And Obese Mice. In: American Journal of Respiratory and Critical Care Medicine. 2015 ; Vol. B30. pp. 2691-2691.
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abstract = "Introduction: Intermittent hypoxia (IH) as a hallmark feature of obstructive sleep apnea (OSA) is a major pathophysiological trigger for cardiovascular and metabolic diseases occurring in OSA. Obesity and OSA may interact in cardiometabolic processes and IH has been suggested to mediate its action through the visceral adipose tissue (AT) promoting a pro-inflammatory response. Metabolically dysfunctional AT in obesity is characterized by macrophage infiltration and polarization of macrophages towards a pro-inflammatory insulin resistance promoting M1, “classically activated” over an anti M2, “alternatively activated” phenotype. Aim of the study was to investigate the impact of IH on AT M1/M2 relationship in lean and diet-induced obese (DIO) mice. Methods: Male C57Bl/6 mice (5-weeks old) were fed on a low-fat diet (LF, 10{\%}fat, n=20) or on a high-fat diet (HF, 60{\%} fat, n=26) for 14 weeks and then randomized to 6 weeks of IH (inspired oxygen 5-21{\%}, 60 sec cycle, 8hrs/day) or intermittent normoxia (N). Insulin tolerance test (ITT) was performed at the end of the protocol. M1 and M2 populations of the stromal vascular fraction of epididymal AT were assessed by flow cytometry.Results: As expected, HF-IH mice were significantly lighter than HF-N at the end of the study, but there was no difference in weight between LF-IH and LF-N. IH contributed to insulin resistance in both, LF and HF and this was associated with higher percentage of AT M1 macrophages (LF: N vs IH: 1.5±0.4{\%} vs 4.3±3.7; p=0.049; HF: 6.8±2.8 vs 11.8±3.8; p=0.009). HF mice demonstrated lower M2 than LF mice (p=0.022) but there was no difference between groups on IH and N treatment.Conclusion: IH contributes to pro-inflammatory macrophage polarization in AT and insulin resistance. Further studies will determine the intermediate mechanisms underlying these events.",
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Chronic Intermittent Hypoxia Contributes To Pro-Inflammatory Macrophage Alteration In Visceral Adipose Tissue Of Lean And Obese Mice. / Murphy, Aoife M; Thomas, Amandine; Tambuwala, Murtaza; McNicholas, Walter T; Roche, Helen M; Taylor, Cormac T; Pepin, Jean-Louis; Arnaud, Claire; Ryan, Silke.

In: American Journal of Respiratory and Critical Care Medicine, Vol. B30, 18.05.2015, p. 2691-2691.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Chronic Intermittent Hypoxia Contributes To Pro-Inflammatory Macrophage Alteration In Visceral Adipose Tissue Of Lean And Obese Mice

AU - Murphy, Aoife M

AU - Thomas, Amandine

AU - Tambuwala, Murtaza

AU - McNicholas, Walter T

AU - Roche, Helen M

AU - Taylor, Cormac T

AU - Pepin, Jean-Louis

AU - Arnaud, Claire

AU - Ryan, Silke

PY - 2015/5/18

Y1 - 2015/5/18

N2 - Introduction: Intermittent hypoxia (IH) as a hallmark feature of obstructive sleep apnea (OSA) is a major pathophysiological trigger for cardiovascular and metabolic diseases occurring in OSA. Obesity and OSA may interact in cardiometabolic processes and IH has been suggested to mediate its action through the visceral adipose tissue (AT) promoting a pro-inflammatory response. Metabolically dysfunctional AT in obesity is characterized by macrophage infiltration and polarization of macrophages towards a pro-inflammatory insulin resistance promoting M1, “classically activated” over an anti M2, “alternatively activated” phenotype. Aim of the study was to investigate the impact of IH on AT M1/M2 relationship in lean and diet-induced obese (DIO) mice. Methods: Male C57Bl/6 mice (5-weeks old) were fed on a low-fat diet (LF, 10%fat, n=20) or on a high-fat diet (HF, 60% fat, n=26) for 14 weeks and then randomized to 6 weeks of IH (inspired oxygen 5-21%, 60 sec cycle, 8hrs/day) or intermittent normoxia (N). Insulin tolerance test (ITT) was performed at the end of the protocol. M1 and M2 populations of the stromal vascular fraction of epididymal AT were assessed by flow cytometry.Results: As expected, HF-IH mice were significantly lighter than HF-N at the end of the study, but there was no difference in weight between LF-IH and LF-N. IH contributed to insulin resistance in both, LF and HF and this was associated with higher percentage of AT M1 macrophages (LF: N vs IH: 1.5±0.4% vs 4.3±3.7; p=0.049; HF: 6.8±2.8 vs 11.8±3.8; p=0.009). HF mice demonstrated lower M2 than LF mice (p=0.022) but there was no difference between groups on IH and N treatment.Conclusion: IH contributes to pro-inflammatory macrophage polarization in AT and insulin resistance. Further studies will determine the intermediate mechanisms underlying these events.

AB - Introduction: Intermittent hypoxia (IH) as a hallmark feature of obstructive sleep apnea (OSA) is a major pathophysiological trigger for cardiovascular and metabolic diseases occurring in OSA. Obesity and OSA may interact in cardiometabolic processes and IH has been suggested to mediate its action through the visceral adipose tissue (AT) promoting a pro-inflammatory response. Metabolically dysfunctional AT in obesity is characterized by macrophage infiltration and polarization of macrophages towards a pro-inflammatory insulin resistance promoting M1, “classically activated” over an anti M2, “alternatively activated” phenotype. Aim of the study was to investigate the impact of IH on AT M1/M2 relationship in lean and diet-induced obese (DIO) mice. Methods: Male C57Bl/6 mice (5-weeks old) were fed on a low-fat diet (LF, 10%fat, n=20) or on a high-fat diet (HF, 60% fat, n=26) for 14 weeks and then randomized to 6 weeks of IH (inspired oxygen 5-21%, 60 sec cycle, 8hrs/day) or intermittent normoxia (N). Insulin tolerance test (ITT) was performed at the end of the protocol. M1 and M2 populations of the stromal vascular fraction of epididymal AT were assessed by flow cytometry.Results: As expected, HF-IH mice were significantly lighter than HF-N at the end of the study, but there was no difference in weight between LF-IH and LF-N. IH contributed to insulin resistance in both, LF and HF and this was associated with higher percentage of AT M1 macrophages (LF: N vs IH: 1.5±0.4% vs 4.3±3.7; p=0.049; HF: 6.8±2.8 vs 11.8±3.8; p=0.009). HF mice demonstrated lower M2 than LF mice (p=0.022) but there was no difference between groups on IH and N treatment.Conclusion: IH contributes to pro-inflammatory macrophage polarization in AT and insulin resistance. Further studies will determine the intermediate mechanisms underlying these events.

KW - Hypoxia

KW - inflammation

KW - mice

M3 - Article

VL - B30

SP - 2691

EP - 2691

JO - American Journal of Respiratory and Critical Care Medicine

T2 - American Journal of Respiratory and Critical Care Medicine

JF - American Journal of Respiratory and Critical Care Medicine

SN - 1073-449X

ER -