Autophagy, an evolutionary conserved process aimed at recycling damaged 
organelles and protein aggregates in the cell, also modulates proinflammatory 
cytokine production in peripheral blood mononuclear cells. Because adipose 
tissue inflammation accompanied by elevated levels of proinflammatory cytokines 
is characteristic for the development of obesity, we hypothesized that 
modulation of autophagy alters adipose tissue inflammatory gene expression and 
secretion. We tested our hypothesis using ex vivo and in vivo studies of human 
and mouse adipose tissue. Levels of the autophagy marker LC3 were elevated in sc 
adipose tissue of obese vs. lean human subjects and positively correlated to 
both systemic insulin resistance and morphological characteristics of adipose 
tissue inflammation. Similarly, autophagic activity levels were increased in 
adipose tissue of obese and insulin resistant animals as compared with lean 
mice. Inhibition of autophagy by 3-methylalanine in human and mouse adipose 
tissue explants led to a significant increase in IL-1β, IL-6, and IL-8 mRNA 
expression and protein secretion. Noticeably, the enhancement in IL-1β, IL-6, 
and keratinocyte-derived chemoattractant (KC) by inhibition of autophagy was 
more robust in the presence of obesity. Similar results were obtained by 
blocking autophagy using small interfering RNA targeted to ATG7 in human 
Simpson-Golabi-Behmel syndrome adipocytes. Our results demonstrate that 
autophagy activity is up-regulated in the adipose tissue of obese individuals 
and inhibition of autophagy enhances proinflammatory gene expression both in 
adipocytes and adipose tissue explants. Autophagy may function to dampen 
inflammatory gene expression and thereby limit excessive inflammation in adipose 
tissue during obesity.