Studies have implicated the extracellular matrix (ECM) of adipose tissue in
insulin resistance. The
proteoglycan decorin, a component of ECM, has been associated with
glucose tolerance, but possible causal effects on metabolism remain to be explored. We here sought to determine metabolic consequences of loss of
decorin in mice (DcnKO). DcnKO mice were fed a low-fat (LF) or high-fat (HF) diet for 10 weeks and
body weight and food intake was recorded. An intraperitoneal
glucose tolerance test was performed after eight weeks. Blood samples and adipose, liver and muscle tissues were collected at sacrifice. Global gene expression was measured in adipose tissue, and expression of
decorin was also analyzed in human adipose samples. DcnKO mice showed increased feed efficiency during overfeeding and
impaired glucose tolerance. Adipose
leptin mRNA and circulating
leptin levels were elevated in DcnKO mice, along with a downregulation of genes involved in ECM organization and
triglyceride biosynthesis, and an upregulation of adipose genes involved in
complement and coagulation cascades. Consistent with a protective metabolic role for
decorin, in obese patients we found increased adipose
decorin expression after profound fat loss, particularly in the stromal vascular fraction. Loss of
decorin in mice caused
impaired glucose tolerance in association with increased feed efficiency and altered gene expression in adipose tissue. Our data provide evidence that
decorin is an important factor for maintaining
glucose tolerance.