Loss of periostin occurs in aging adipose tissue of mice and its genetic ablation impairs adipose tissue lipid metabolism

Aging Cell. 2018 Oct;17(5):e12810. doi: 10.1111/acel.12810. Epub 2018 Aug 7.

Abstract

Remodeling of the extracellular matrix is a key component of the metabolic adaptations of adipose tissue in response to dietary and physiological challenges. Disruption of its integrity is a well-known aspect of adipose tissue dysfunction, for instance, during aging and obesity. Adipocyte regeneration from a tissue-resident pool of mesenchymal stem cells is part of normal tissue homeostasis. Among the pathophysiological consequences of adipogenic stem cell aging, characteristic changes in the secretory phenotype, which includes matrix-modifying proteins, have been described. Here, we show that the expression of the matricellular protein periostin, a component of the extracellular matrix produced and secreted by adipose tissue-resident interstitial cells, is markedly decreased in aged brown and white adipose tissue depots. Using a mouse model, we demonstrate that the adaptation of adipose tissue to adrenergic stimulation and high-fat diet feeding is impaired in animals with systemic ablation of the gene encoding for periostin. Our data suggest that loss of periostin attenuates lipid metabolism in adipose tissue, thus recapitulating one aspect of age-related metabolic dysfunction. In human white adipose tissue, periostin expression showed an unexpected positive correlation with age of study participants. This correlation, however, was no longer evident after adjusting for BMI or plasma lipid and liver function biomarkers. These findings taken together suggest that age-related alterations of the adipose tissue extracellular matrix may contribute to the development of metabolic disease by negatively affecting nutrient homeostasis.

Keywords: adipogenic progenitor cells; adipose tissue; aging; extracellular matrix; fatty acid metabolism; periostin.

MeSH terms

  • Adipose Tissue / drug effects
  • Adipose Tissue / metabolism*
  • Adipose Tissue / pathology*
  • Adrenergic Agents / pharmacology
  • Adult
  • Aged
  • Aged, 80 and over
  • Aging / metabolism*
  • Animals
  • Body Size / drug effects
  • Cell Adhesion Molecules / deficiency*
  • Cell Adhesion Molecules / genetics*
  • Cell Adhesion Molecules / metabolism
  • Cold Temperature
  • Diet, High-Fat
  • Enzyme Activation / drug effects
  • Feeding Behavior
  • Female
  • Gene Deletion*
  • Humans
  • Lipid Metabolism* / drug effects
  • Male
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Middle Aged
  • Obesity / pathology
  • Organ Size / drug effects
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Sterol Esterase / metabolism
  • Thermogenesis / drug effects
  • Young Adult

Substances

  • Adrenergic Agents
  • Cell Adhesion Molecules
  • POSTN protein, human
  • Postn protein, mouse
  • RNA, Messenger
  • Sterol Esterase