Inhibiting Autogaphy in Adipocytes May Prevent Age-Related Metabolic Disorders

A research team at Osaka University has discovered how changes in the adipose tissue can lead to the onset of metabolic disorders. The study was published in Nature Communications. 

"Adipocytes produce hormones and cytokines that regulate the function of other metabolic organs," says study lead author Tadashi Yamamuro. "Age-related changes in adipose tissue result in metabolic disorders that are closely associated with life-threatening cardiovascular diseases. However, no one really knows what causes adipocyte dysfunction in aged organisms."

The team decided to focus on autophagy since previous studies had shown that autophagy plays a role in the aging process. Specifically, they wanted to understand how autophagy becomes crucial for the normal function and longevity of organs. 

"We previously showed that a protein called Rubicon, which inhibits autophagy, is upregulated in aging tissues. We, therefore, hypothesized that Rubicon likely accumulates in aged adipocytes, decreasing autophagic activity, and contributing to the onset of metabolic disorders," says Yamamuro. Instead, the team found that Rubicon levels were decreased in the adipose tissue of aged mice, increasing autophagic activity. Researchers then developed a mouse line in which Rubicon was specifically inactivated in adipose tissue.

"In the absence of Rubicon, we observed excessive autophagy in adipocytes and a decline in adipocyte function," explains senior author Tamotsu Yoshimori. Despite being fed the same diet as control animals, the Rubicon deletion mice developed lifestyle diseases such as fatty liver and diabetes. Furthermore, through their analysis, the team was able to identify the proteins affected by the increased levels of autophagy, showing that supplementation of these proteins restored adipocyte function.

"This is a really exciting discovery with important therapeutic implications," says Yoshimori. "Because age-dependent loss of adipose Rubicon causes lifestyle diseases via excess autophagy, inhibiting autophagy in adipocytes may help prevent the onset of these prevalent and potentially life-threatening conditions."