Newswise – Osaka, Japan – The arrival of spring heralds spring cleaning; a time to declutter your home and throw away things you no longer need. In the body, a cellular process called autophagy occurs regularly to “declutter” our cells. Recently, researchers in Japan shed new light on the relationship between this process and the body’s metabolic response to fasting.
In a new study published in Autophagy, researchers led by Osaka University studied the role of autophagy. Autophagy is the process by which unwanted cellular components are removed by degradation, during fasting conditions.
Previous studies have shown that fasting causes fatty tissue, also known as adipose tissue, to break down, leading to fatty liver disease (a buildup of fat in the liver) and ketogenesis (the production of ketones, which are by-products fat breakdown). ). A gene called Rubicon Autophagy Regulator (RUBCN) acts as a negative autophagy regulator, meaning it works to suppress autophagy. The Osaka University-led research team previously demonstrated that the loss of RUBCN from adipose tissue during aging leads to systemic fat loss. Since RUBCN levels are also reduced during fasting, the researchers hypothesized that this reduction may promote fat loss through upregulation of autophagy.
“We wanted to deepen our understanding of how autophagy is involved in the body’s metabolic response to fasting,” says lead author Tadashi Yamamuro. “To do this, we assessed the effects of modulating autophagy in fat cells from fed and fasted mice.”
The researchers used several mouse models to perform their investigation, including a specific fat model lacking RUBCN and a specific fat model lacking ATG5, a gene essential for autophagy. Fat loss, triglyceride levels, and liver weight were assessed in these mice and compared to control mice under fed and fasted conditions.
“In control mice, fat loss, hepatic steatosis, and serum ketones were observed under fasting conditions,” says lead author Tamotsu Yoshimori. “Fed RUBCN knockout mice showed similar responses to fasted control mice, while fasted ATG5 mice showed reductions in fat loss, fatty liver, and serum ketones.”
The researchers also found that fasted control mice showed a substantial decrease in the expression of adipogenic or fat-promoting genes. In ATG5 knockout mice, this reduction was not observed, indicating that autophagy plays a role in reducing adipogenic gene expression.
Taken together with the results of the research team’s previous study, it appears that upregulation of autophagy in adipose tissue is a hallmark of fasting and aging. In addition to revealing a previously unknown mechanism of the fasting response, these findings may have important implications for our understanding of metabolism during aging.
The article, “Loss of RUBCN/rubicon in adipocytes mediates upregulation of autophagy to promote response to fasting,” was published in Autophagy at DOI: https://doi.org/10.1080/15548627.2022.2047341
About Osaka University
Osaka University was founded in 1931 as one of Japan’s Seven Imperial Universities and today is one of Japan’s leading comprehensive universities with a wide range of disciplines. This strength is coupled with a singular desire for innovation that extends throughout the scientific process, from basic research to the creation of applied technologies with positive economic spinoffs. Its commitment to innovation has been recognized in Japan and around the world, being named Japan’s most innovative university in 2015 (Reuters 2015 Top 100) and one of the world’s most innovative institutions in 2017 (Innovative Universities and the Nature Index Innovation 2017). Today, Osaka University leverages its role as a designated national university society selected by the Ministry of Education, Culture, Sports, Science and Technology to contribute innovation for human well-being, sustainable development of society and social transformation.