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Your search keyword '"Mamane, A."' showing total 2 results
Start Over Author "Mamane, A." Publisher american diabetes association
2 results on '"Mamane, A."'

1. The C3a anaphylatoxin receptor is a key mediator of insulin resistance and functions by modulating adipose tissue macrophage infiltration and activation

Author

Mamane, Yael, Chan, Chi Chung, Lavallee, Genevieve, Morin, Nicolas, Xu, Li-Jing, Huang, JingQi, Gordon, Robert, Thomas, Winston, Lamb, John, Schadt, Eric E., Kennedy, Brian P., and Mancini, Joseph A.

Subjects
Type 2 diabetes -- Genetic aspects, Type 2 diabetes -- Development and progression, Type 2 diabetes -- Risk factors, Macrophages -- Genetic aspects, Macrophages -- Health aspects, Atherosclerosis -- Genetic aspects, Atherosclerosis -- Risk factors, Atherosclerosis -- Development and progression, Adipose tissues -- Genetic aspects, Adipose tissues -- Properties, Insulin resistance -- Genetic aspects, Obesity -- Genetic aspects, Obesity -- Risk factors, Health
Abstract

OBJECTIVE--Significant new data suggest that metabolic disorders such as diabetes, obesity, and atherosclerosis all posses an important inflammatory component. Infiltrating macrophages contribute to both tissue-specific and systemic inflammation, which promotes insulin resistance. The complement cascade is involved in the inflammatory cascade initiated by the innate and adaptive immune response. A mouse genomic F2 cross biology was performed and identified several causal genes linked to type 2 diabetes, including the complement pathway. RESEARCH DESIGN AND METHODS--We therefore sought to investigate the effect of a C3a receptor (C3aR) deletion on insulin resistance, obesity, and macrophage function utilizing both the normal-diet (ND) and a diet-induced obesity mouse model. RESULTS--We demonstrate that high C3aR expression is found in white adipose tissue and increases upon high-fat diet (HFD) feeding. Both adipocytes and macrophages within the white adipose tissue express significant amounts of C3aR. [C3aR.sup.-/-] mice on HFD are transiently resistant to diet-induced obesity during an 8-week period. Metabolic profiling suggests that they are also protected from HFD-induced insulin resistance and liver steatosis. [C3aR.sup.-/-] mice had improved insulin sensitivity on both ND and HFD as seen by an insulin tolerance test and an oral glucose tolerance test. Adipose tissue analysis revealed a striking decrease in macrophage infiltration with a concomitant reduction in both tissue and plasma proinflammatory cytokine production. Furthermore, [C3aR.sup.-/-] macrophages polarized to the M1 phenotype showed a considerable decrease in proinflammatory mediators. CONCLUSIONS--Overall, our results suggest that the C3aR in macrophages, and potentially adipocytes, plays an important role in adipose tissue homeostasis and insulin resistance., The complement system is an integral part of both the innate and adaptive immune response involved in the defense against invading pathogens (1). Complement activation culminates in a massive amplification [...]

Published
2009

2. The C3a Anaphylatoxin Receptor Is a Key Mediator of Insulin Resistance and Functions by Modulating Adipose Tissue Macrophage Infiltration and Activation

Author

Genevieve Lavallee, Brian P. Kennedy, Yaël Mamane, Nicolas Morin, Lijing Xu, John Lamb, R. Gordon, JingQi Huang, Joseph A. Mancini, Eric E. Schadt, Chi-Chung Chan, and Winston Thomas

Subjects
Male, medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, Adipose tissue macrophages, Adipose tissue, Inflammation, White adipose tissue, Biology, Proinflammatory cytokine, Mice, Insulin resistance, Cell Movement, 3T3-L1 Cells, Internal medicine, Internal Medicine, medicine, Animals, Homeostasis, Hypoglycemic Agents, Insulin, Obesity, Macrophages, Insulin tolerance test, medicine.disease, Dietary Fats, Mice, Mutant Strains, Receptors, Complement, Mice, Inbred C57BL, Metabolism, Phenotype, Endocrinology, Adipose Tissue, Original Article, Insulin Resistance, medicine.symptom
Abstract

OBJECTIVESignificant new data suggest that metabolic disorders such as diabetes, obesity, and atherosclerosis all posses an important inflammatory component. Infiltrating macrophages contribute to both tissue-specific and systemic inflammation, which promotes insulin resistance. The complement cascade is involved in the inflammatory cascade initiated by the innate and adaptive immune response. A mouse genomic F2 cross biology was performed and identified several causal genes linked to type 2 diabetes, including the complement pathway.RESEARCH DESIGN AND METHODSWe therefore sought to investigate the effect of a C3a receptor (C3aR) deletion on insulin resistance, obesity, and macrophage function utilizing both the normal-diet (ND) and a diet-induced obesity mouse model.RESULTSWe demonstrate that high C3aR expression is found in white adipose tissue and increases upon high-fat diet (HFD) feeding. Both adipocytes and macrophages within the white adipose tissue express significant amounts of C3aR. C3aR−/− mice on HFD are transiently resistant to diet-induced obesity during an 8-week period. Metabolic profiling suggests that they are also protected from HFD-induced insulin resistance and liver steatosis. C3aR−/− mice had improved insulin sensitivity on both ND and HFD as seen by an insulin tolerance test and an oral glucose tolerance test. Adipose tissue analysis revealed a striking decrease in macrophage infiltration with a concomitant reduction in both tissue and plasma proinflammatory cytokine production. Furthermore, C3aR−/− macrophages polarized to the M1 phenotype showed a considerable decrease in proinflammatory mediators.CONCLUSIONSOverall, our results suggest that the C3aR in macrophages, and potentially adipocytes, plays an important role in adipose tissue homeostasis and insulin resistance.

Published
2009

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