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

Antonia Graja,Siegfried Ussar,Anne‐Marie Jank,Tim J Schulz,Matthias Blüher,Matthias Kern,Francisco Garcia‐Carrizo,Thomas H Ambrosi,Annette Schürmann,Sabrina Gohlke,Krasimira Aleksandrova,Wenke Jonas

doi:10.1111/acel.12810

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.

Highlights

Aging is associated with increased body weight gain (Chumlea et al, 2002)
These data suggest that the deletion of periostin leads to impaired lipid metabolism in adipose tissues during high‐fat diet (HFD) feeding which is consistent with the defective metabolic response observed during cold exposure
Aging is associated with defective extracellular matrix (ECM) function leading to tissue fibrosis, that is, an excessive accumulation of fibrous connective tissue and ECM components (Wynn, 2007)

Summary

| INTRODUCTION

Aging is associated with increased body weight gain (Chumlea et al, 2002). Overweight is a risk factor for the metabolic syndrome and promotes progression of different pathologies (Rosen & Spiegelman, 2014). Aside from adipocytes, adipose tissue‐resident mesenchymal stem cells are a main source of secreted signals. Their secretory profile, which includes matrix‐modifying enzymes, changes significantly with increased age (Tchkonia et al, 2010). While aging results in a marked downregulation of Postn expression, metabolic interventions that require adipose tissue remodeling induce Postn gene expression. In line with these observations, systemic deletion of Postn in mice resulted in loss of adipose tissue (AT) mass after cold exposure, reduced AT expansion and adipocyte size during high‐fat diet (HFD) feeding, and impaired lipolytic enzyme activity after acute β3‐adrenergic stimulation. The age‐related correlation could partially be explained by changes to BMI, as well as plasma lipid and liver biomarkers

| RESULTS

| DISCUSSION

| EXPERIMENTAL PROCEDURES

Findings

CONFLICT OF INTEREST