Acute-Phase Serum Amyloid A as a Marker of Insulin Resistance in Mice

Acute-phase serum amyloid A (A-SAA) was shown recently to correlate with obesity and insulin resistance in humans. However, the mechanisms linking obesity-associated inflammation and elevated plasma A-SAA to insulin resistance are poorly understood. Using high-fat diet- (HFD-) fed mice, we found that plasma A-SAA was increased early upon HFD feeding and was tightly associated with systemic insulin resistance. Plasma A-SAA elevation was due to induction of Saa1 and Saa2 expression in liver but not in adipose tissue. In adipose tissue Saa3 was the predominant isoform and the earliest inflammatory marker induced, suggesting it is important for initiation of adipose tissue inflammation. To assess the potential impact of A-SAA on adipose tissue insulin resistance, we treated 3T3-L1 adipocytes with recombinant A-SAA. Intriguingly, physiological levels of A-SAA caused alterations in gene expression closely resembling those observed in HFD-fed mice. Proinflammatory genes (Ccl2, Saa3) were induced while genes critical for insulin sensitivity (Irs1, Adipoq, Glut4) were down-regulated. Our data identify HFD-fed mice as a suitable model to study A-SAA as a biomarker and a novel possible mediator of insulin resistance.

• Publication year

  2008

• Venue

  International Journal of Experimental Diabetes Research

• Publication date

  2008-06-22

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1155/2008/230837PMID 18584041PMCID 2435226
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Serum amyloid A

  2010cited by this paper
• Macrophages block insulin action in adipocytes by altering expression of signaling and glucose transport proteins.

  2007cited by this paper
• Adipocyte-Derived Serum Amyloid A3 and Hyaluronan Play a Role in Monocyte Recruitment and Adhesion

  2007cited by this paper
• MCP-1 contributes to macrophage infiltration into adipose tissue, insulin resistance, and hepatic steatosis in obesity.

  2006cited by this paper
• Sterol regulatory element-binding protein 1 mediates liver X receptor-beta-induced increases in insulin secretion and insulin messenger ribonucleic acid levels.

  2006cited by this paper
• Inflammation and metabolic disorders

  2006cited by this paper
• Serum Amyloid A Is an Endogenous Ligand That Differentially Induces IL-12 and IL-231

  2006cited by this paper
• Acute-Phase Serum Amyloid A: An Inflammatory Adipokine and Potential Link between Obesity and Its Metabolic Complications

  2006cited by this paper
• Serum Amyloid A: A Marker of Adiposity‐induced Low‐grade Inflammation but Not of Metabolic Status

  2006cited by this paper
• Serum Amyloid A Promotes Cholesterol Efflux Mediated by Scavenger Receptor B-I*

  2005cited by this paper
• Serum Amyloid A and Lipoprotein Retention in Murine Models of Atherosclerosis

  2005cited by this paper
• Cholesterol Feeding Increases C-Reactive Protein and Serum Amyloid A Levels in Lean Insulin-Sensitive Subjects

  2005cited by this paper
• A microarray search for genes predominantly expressed in human omental adipocytes: adipose tissue as a major production site of serum amyloid A.

  2005cited by this paper
• Serum Amyloid A Is a Ligand for Scavenger Receptor Class B Type I and Inhibits High Density Lipoprotein Binding and Selective Lipid Uptake*

  2005cited by this paper
• Local expression of the serum amyloid A and formyl peptide receptor-like 1 genes in synovial tissue is associated with matrix metalloproteinase production in patients with inflammatory arthritis.

  2004cited by this paper
• Increase in Serum Amyloid A Evoked by Dietary Cholesterol Is Associated With Increased Atherosclerosis in Mice

  2004cited by this paper
• Cholesterol and Cholate Components of an Atherogenic Diet Induce Distinct Stages of Hepatic Inflammatory Gene Expression*

  2003cited by this paper
• Induction of human mammary-associated serum amyloid A3 expression by prolactin or lipopolysaccharide.

  2003cited by this paper
• Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance.

  2003influential reference
• Obesity is associated with macrophage accumulation in adipose tissue.

  2003influential reference
• Tumor necrosis factor-α suppresses adipocyte-specific genes and activates expression of preadipocyte genes in 3T3-L1 adipocytes: Nuclear factor-κB activation by TNF-α is obligatory

  2002cited by this paper
• Differential transcription of the mouse acute phase serum amyloid A genes in response to pro-inflammatory cytokines

  2002influential reference
• Tumor necrosis factor-alpha suppresses adipocyte-specific genes and activates expression of preadipocyte genes in 3T3-L1 adipocytes: nuclear factor-kappaB activation by TNF-alpha is obligatory.

  2002cited by this paper
• Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method.

  2001cited by this paper
• Hyperglycemia-induced Production of Acute Phase Reactants in Adipose Tissue*

  2001cited by this paper
• C-reactive protein and other markers of inflammation in the prediction of cardiovascular disease in women.

  2000cited by this paper
• Role of serum amyloid A during metabolism of acute-phase HDL by macrophages.

  2000cited by this paper
• Troglitazone reduces hyperglycaemia and selectively acute-phase serum proteins in patients with Type II diabetes

  1999cited by this paper
• Acute-phase proteins and other systemic responses to inflammation.

  1999cited by this paper
• Serum amyloid A, the major vertebrate acute-phase reactant.

  1999influential reference
• Human Serum Amyloid A has Cytokine‐Like Properties

  1998cited by this paper
• NIDDM as a disease of the innate immune system: association of acute-phase reactants and interleukin-6 with metabolic syndrome X

  1997cited by this paper
• Association between serum amyloid A proteins and coronary artery disease: evidence from two distinct arteriosclerotic processes.

  1997cited by this paper
• The prognostic value of C-reactive protein and serum amyloid a protein in severe unstable angina.

  1994cited by this paper
• Genetic evidence for a common pathway mediating oxidative stress, inflammatory gene induction, and aortic fatty streak formation in mice.

  1994cited by this paper
• Serum amyloid A protein family. Differential induction by oxidized lipids in mouse strains.

  1994cited by this paper
• Serum amyloid A is a chemoattractant: induction of migration, adhesion, and tissue infiltration of monocytes and polymorphonuclear leukocytes

  1994cited by this paper
• Analysis of Relative Gene Expression Data Using Real-Time Quantitative PCR and the 2 2 DD C T Method

  year unknowncited by this paper

• Serum amyloid A in HFpEF and cardiometabolic diseases

  2025cites this paper
• Acute peripheral versus central inhibition of insulin receptors differentially alters cytokine and blood-brain barrier responses to an inflammatory stimulus.

  2025cites this paper
• Prognostic impacts of lipoxin A4 in relation to diabetes and insulin resistance in patients with acute myocardial infarction: a prospective study

  2025cites this paper
• A 1.1 Mb duplication CNV on chromosome 17 contributes to skeletal muscle development in Boer goats

  2023cites this paper
• Association between Serum Amyloid A Levels and Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis

  2023cites this paper
• Serum amyloid A and metabolic disease: evidence for a critical role in chronic inflammatory conditions

  2023cites this paper
• SAA1 exacerbates pancreatic β-cell dysfunction through activation of NF-κB signaling in high-fat diet-induced type 2 diabetes mice.

  2023cites this paper
• Convicting a wrong molecule?

  2023cites this paper
• Flavin-Containing Monooxygenase 3 (FMO3) Is Critical for Dioxin-Induced Reorganization of the Gut Microbiome and Host Insulin Sensitivity

  2022cites this paper
• The Association of Acute Phase Proteins in Stress and Inflammation-Induced T2D

  2022cites this paper
• A SNP in the 5’ flanking region of the SAA1 gene is associated with serum levels of serum amyloid A and cardiovascular risk factors

  2022cites this paper
• The Effects of Eight Weeks Moderate- and High-Intensity Circuit Resistance Training on the Levels of Serum Amyloid A and Insulin Resistance in Sedentary Men

  2022cites this paper
• High lipid diet and the expression of proinflammatory markers in testis.

  2022cites this paper
• The Impact of Maternal and Piglet Low Protein Diet and Their Interaction on the Porcine Liver Transcriptome around the Time of Weaning

  2021cites this paper
• Cysteine 253 of UCP1 regulates energy expenditure and sex-dependent adipose tissue inflammation.

  2021cites this paper
• Identification of Novel Biomarkers for Pre-diabetic Diagnosis Using a Combinational Approach

  2021cites this paper
• Sex dimorphism in inflammatory response to obesity in childhood

  2021cites this paper
• Serum amyloid A in polycystic ovary syndrome.

  2021cites this paper
• Adipose-Derived Molecules–Untouched Horizons in Alzheimer’s Disease Biology

  2020cites this paper
• Influence of Metabolic Status and Diet on Early Pregnant Equine Histotroph Proteome: Preliminary Findings.

  2020cites this paper
• Effects of advanced age and pituitary pars intermedia dysfunction on components of the acute phase reaction in horses.

  2020cites this paper
• Effects of equine metabolic syndrome on inflammation and acute-phase markers in horses.

  2020cites this paper
• Acute phase reactant serum amyloid A in inflammation and other diseases.

  2019cites this paper
• Fpr2 Deficiency Alleviates Diet-Induced Insulin Resistance Through Reducing Body Weight Gain and Inhibiting Inflammation Mediated by Macrophage Chemotaxis and M1 Polarization

  2019cites this paper
• Progressive circuit resistance training improves inflammatory biomarkers and insulin resistance in obese men.

  2019cites this paper
• Impact of drug distribution into adipose on tissue function: The cholesteryl ester transfer protein (CETP) inhibitor anacetrapib as a test case

  2019cites this paper
• Contribution of Adipose Tissue Inflammation to the Development of Type 2 Diabetes Mellitus.

  2018cites this paper
• Intestinal Serum amyloid A suppresses systemic neutrophil activation and bactericidal activity in response to microbiota colonization

  2018cites this paper
• Type 2 diabetes-related proteins derived from an in vitro model of inflamed fat tissue.

  2018cites this paper
• Adaptive Immunity and Metabolic Health: Harmony Becomes Dissonant in Obesity and Aging.

  2017cites this paper
• Magnitude and Timing of the Postprandial Inflammatory Response to a High-Fat Meal in Healthy Adults: A Systematic Review.

  2017cites this paper
• A human stool-derived Bilophila wadsworthia strain caused systemic inflammation in specific-pathogen-free mice

  2017cites this paper
• Lipid diets affect the host-microbe dynamic in the gut

  2017cites this paper
• Regulation of cardiometabolic risk factors by dietary Toll-like receptor stimulants

  2017cites this paper
• Serum amyloid A links endotoxaemia to weight gain and insulin resistance in mice

  2016cites this paper
• Novel targets for the development of drugs for Type 2 Diabetes Mellitus

  2016cites this paper
• Serum amyloid A1 levels and amyloid deposition following a high-fat diet challenge in transgenic mice overexpressing hepatic serum amyloid A1.

  2016cites this paper
• Age‐associated vascular inflammation promotes monocytosis during atherogenesis

  2016cites this paper
• Gut Microbiome and Obesity: A Review of Literature

  2016cites this paper
• Dietary fat drives whole-body insulin resistance and promotes intestinal inflammation independent of body weight gain.

  2016cites this paper
• Effect of ascorbic acid and alpha-tocopherol supplementations on serum leptin, tumor necrosis factor alpha, and serum amyloid A levels in individuals with type 2 diabetes mellitus

  2015cites this paper
• Acute‐phase protein serum amyloid A3 is a novel paracrine coupling factor that controls bone homeostasis

  2015cites this paper
• Liver immune responses to inflammatory stimuli in a diet-induced obesity model of zebrafish.

  2015cites this paper
• Effect of Chronic Pioglitazone Treatment on Hepatic Gene Expression Profile in Obese C57BL/6J Mice

  2015cites this paper
• Novel Therapies for Diabetic Kidney Disease: Storied Past and Forward Paths

  2015cites this paper
• Central obesity, type 2 diabetes and insulin: exploring a pathway full of thorns

  2015cites this paper
• A natural solution for obesity: Bioactives for the prevention and treatment of weight gain. A review

  2015cites this paper
• High-fat meal induced postprandial inflammation.

  2014cites this paper
• The epithelial-dendritic cell interface in pulmonary disease

  2014cites this paper
• Deletion of Serum Amyloid A3 Improves High Fat High Sucrose Diet-Induced Adipose Tissue Inflammation and Hyperlipidemia in Female Mice

  2014cites this paper
• Aerobic Exercise and Weight Loss Reduce Vascular Markers of Inflammation and Improve Insulin Sensitivity in Obese Women

  2014cites this paper
• Is Acute-phase Serum Amyloid A Protein a Risk Factor for Type 2 Diabetes - Epidemiologic Perspective Including a Genetic Approach

  2014cites this paper
• Metabolic and immunomodulatory effects of n-3 fatty acids are different in mesenteric and epididymal adipose tissue of diet-induced obese mice.

  2013cites this paper
• Acute-Phase Serum Amyloid A Protein and Its Implication in the Development of Type 2 Diabetes in the KORA S4/F4 Study

  2013cites this paper
• No Evidence for a Role of Adipose Tissue-Derived Serum Amyloid A in the Development of Insulin Resistance or Obesity-Related Inflammation in hSAA1+/− Transgenic Mice

  2013influential citation
• Hepatic and extrahepatic expression of serum amyloid A3 during lactation in dairy cows.

  2013cites this paper
• The Lung Inflammation and Skeletal Muscle Wasting Induced by Subchronic Cigarette Smoke Exposure Are Not Altered by a High-Fat Diet in Mice

  2013cites this paper
• Relationships between body condition score and plasma inflammatory cytokines, insulin, and lipids in a mixed population of light-breed horses.

  2013cites this paper
• Homocysteine induces serum amyloid A3 in osteoblasts via unlocking RGD‐motifs in collagen

  2013cites this paper
• A methionine-choline-deficient diet elicits NASH in the immunodeficient mouse featuring a model for hepatic cell transplantation.

  2012cites this paper
• Novel effects of n-3 LC-PUFA on adipose tissue and liver in diet-induced obesity in mice

  2012cites this paper
• SELECTION OF REFERENCE GENES FOR NORMALIZATION OF REAL-TIME PCR DATA IN VISCERAL ADIPOSE TISSUE OF FEMALE RATS ON A FRUCTOSE-ENRICHED DIET

  2012cites this paper
• The gut microbiota and its relationship to diet and obesity

  2012cites this paper
• The Acute Phase Protein Serum Amyloid A Induces Lipolysis and Inflammation in Human Adipocytes through Distinct Pathways

  2012cites this paper
• Folate depletion changes gene expression of fatty acid metabolism, DNA synthesis, and circadian cycle in male mice.

  2012cites this paper
• Differential effects of growth hormone versus insulin-like growth factor-I on the mouse plasma proteome.

  2011cites this paper
• Serum amyloid A is a growth factor for 3T3-L1 adipocytes, inhibits differentiation and promotes insulin resistance

  2011cites this paper
• Establishment of a Transgenic Mouse Model Specifically Expressing Human Serum Amyloid A in Adipose Tissue

  2011cites this paper
• Serum amyloid A in atherosclerosis

  2011cites this paper
• Targeting gut microbiota in obesity: effects of prebiotics and probiotics

  2011cites this paper
• Variable penetrance of metabolic phenotypes and development of high-fat diet-induced adiposity in NEIL1-deficient mice.

  2011cites this paper
• 16. Jahrestagung der Österreichischen Gesellschaft für Endokrinologie und Stoffwechsel 12.-13. Mai 2011, Billrothhaus, Wien Abstracts (in alphabetischer Reihenfolge der Presenting Authors)

  2011cites this paper
• Association between serum amyloid A and obesity: a meta-analysis and systematic review

  2010influential citation
• Regulation of Nutrient Metabolism in Equine Skeletal Muscle and Adipose Tissue

  2010cites this paper
• Diagnosis of Complex Diseases

  2010cites this paper
• Microbial regulation of SAA3 expression in mouse colon and adipose tissue

  2010cites this paper
• Anti-obesity effect of phosphatidylinositol on diet-induced obesity in mice.

  2010cites this paper
• Functional Heterogeneity of CD11c-positive Adipose Tissue Macrophages in Diet-induced Obese Mice*

  2010cites this paper
• Coordinated regulation of the metabolome and lipidome at the host-microbial interface.

  2010cites this paper
• Obesity and the human microbiome

  2010cites this paper
• Atherogenic diets exacerbate colitis in mice deficient in glutathione peroxidase

  2010cites this paper
• Tenomodulin, serum amyloid A and the serum amyloid A receptor selenoprotein S - implications for metabolic disease

  2010cites this paper
• Network Analysis of Hepatic Genes Responded to High-Fat Diet in C57BL/6J Mice: Nutrigenomics Data Mining from Recent Research Findings

  2010cites this paper
• Sex-specific gene expression in the BXD mouse liver.

  2010cites this paper
• Functional characterization of Angptl4 protein

  2009cites this paper
• Serum amyloid A attenuates cellular insulin sensitivity by increasing JNK activity in 3T3-L1 adipocytes

  2009cites this paper
• Upregulation of Tanis mRNA expression in the liver is associated with insulin resistance in rats.

  2009cites this paper
• Regulation of Serum Amyloid A3 (SAA3) in Mouse Colonic Epithelium and Adipose Tissue by the Intestinal Microbiota

  2009influential citation
• Protective effect of dietary antioxidants and plant extracts on acute inflammation and hepatotoxicity in vitro

  2009cites this paper
• Liver TAG Transiently Decreases While PL n-3 and n-6 Fatty Acids are Persistently Elevated in Insulin Resistant Mice

  2008cites this paper