title: SirT1 regulates adipose tissue inflammation.
abstract: OBJECTIVE
  Macrophage recruitment to adipose tissue is a reproducible feature of obesity. However, the events that result in chemokine production and macrophage recruitment to adipose tissue during states of energetic excess are not clear. Sirtuin 1 (SirT1) is an essential nutrient-sensing histone deacetylase, which is increased by caloric restriction and reduced by overfeeding. We discovered that SirT1 depletion causes anorexia by stimulating production of inflammatory factors in white adipose tissue and thus posit that decreases in SirT1 link overnutrition and adipose tissue inflammation.
  
  
  METHODS
  We used antisense oligonucleotides to reduce SirT1 to levels similar to those seen during overnutrition and studied SirT1-overexpressing transgenic mice and fat-specific SirT1 knockout animals. Finally, we analyzed subcutaneous adipose tissue biopsies from two independent cohorts of human subjects.
  
  
  RESULTS
  We found that inducible or genetic reduction of SirT1 in vivo causes macrophage recruitment to adipose tissue, whereas overexpression of SirT1 prevents adipose tissue macrophage accumulation caused by chronic high-fat feeding. We also found that SirT1 expression in human subcutaneous fat is inversely related to adipose tissue macrophage infiltration.
  
  
  CONCLUSIONS
  Reduction of adipose tissue SirT1 expression, which leads to histone hyperacetylation and ectopic inflammatory gene expression, is identified as a key regulatory component of macrophage influx into adipose tissue during overnutrition in rodents and humans. Our results suggest that SirT1 regulates adipose tissue inflammation by controlling the gain of proinflammatory transcription in response to inducers such as fatty acids, hypoxia, and endoplasmic reticulum stress.
authors: Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, Connecticut, USA.
authors: Matthew P
authors: MP
authors: Gillum
authors: Maya E
authors: ME
authors: Kotas
authors: Derek M
authors: DM
authors: Erion
authors: Romy
authors: R
authors: Kursawe
authors: Paula
authors: P
authors: Chatterjee
authors: Kevin T
authors: KT
authors: Nead
authors: Eric S
authors: ES
authors: Muise
authors: Jennifer J
authors: JJ
authors: Hsiao
authors: David W
authors: DW
authors: Frederick
authors: Shin
authors: S
authors: Yonemitsu
authors: Alexander S
authors: AS
authors: Banks
authors: Li
authors: L
authors: Qiang
authors: Sanjay
authors: S
authors: Bhanot
authors: Jerrold M
authors: JM
authors: Olefsky
authors: Dorothy D
authors: DD
authors: Sears
authors: Sonia
authors: S
authors: Caprio
authors: Gerald I
authors: GI
authors: Shulman
mesh_terms: D000273:Adipose Tissue / Q000276:immunology* / Q000378:metabolism*; D052436:Adipose Tissue, White / Q000276:immunology / Q000378:metabolism; D000818:Animals; D015992:Body Mass Index; D004041:Dietary Fats / Q000009:adverse effects; D005434:Flow Cytometry; D006801:Humans; D066298:In Vitro Techniques; D007249:Inflammation / Q000139:chemically induced / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D056564:Sirtuin 1 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D015431:Weight Loss / Q000235:genetics / Q000502:physiology
chemical_list: D004041:Dietary Fats; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D056564:Sirtuin 1