Is turning back the clock in aging fat cells a remedy for lifestyle diseases?

August 18, 2020

Osaka, Japan - No matter how much we try and fight it, aging is a part of life. High cholesterol, diabetes, and fatty liver, the collection of conditions referred to as lifestyle diseases, all become more commonplace as we get older. Interestingly, however, many of these age-related conditions are caused by changes inside adipocytes, the fat cells responsible for storing excess energy.

Now, in a study published in Nature Communications, researchers led by Osaka University have uncovered exactly how these changes lead to the onset of lifestyle diseases, with an eye to reversing the process.

"Adipocytes produce hormones and cytokines that regulate the function of other metabolic organs," explains 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 research team decided to focus on autophagy, the process used by cells to eliminate unwanted or dysfunctional cellular components. Previous studies had shown that autophagy plays an important role in the prevention of various age-related disorders and is likely to be involved in the aging process. But most pertinent was the finding that autophagy is essential for the normal function and longevity of normal organs, such as liver or kidney.

Says Yamamuro, "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."

Surprisingly though, the researchers found that Rubicon levels were actually decreased in the adipose tissue of aged mice, resulting in increased autophagic activity.

To dig deeper into the underlying mechanism, the researchers 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. "As a result, the mice developed lifestyle diseases such as diabetes and fatty liver and had significantly higher cholesterol levels, despite being fed the same diet as control animals."

The researchers went on to identify the specific proteins affected by the increased levels of autophagy, showing that supplementation of these proteins in the Rubicon deletion mice 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."
-end-
The article, "Age-dependent loss of adipose Rubicon promotes metabolic disorders via excess autophagy," was published in Nature Communications at DOI: https://doi.org/10.1038/s41467-020-17985-w

About Osaka University

Osaka University was founded in 1931 as one of the seven imperial universities of Japan and is now one of Japan's leading comprehensive universities with a broad disciplinary spectrum. This strength is coupled with a singular drive for innovation that extends throughout the scientific process, from fundamental research to the creation of applied technology with positive economic impacts. 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 most innovative institutions in the world in 2017 (Innovative Universities and the Nature Index Innovation 2017). Now, Osaka University is leveraging its role as a Designated National University Corporation selected by the Ministry of Education, Culture, Sports, Science and Technology to contribute to innovation for human welfare, sustainable development of society, and social transformation.

Website: https://resou.osaka-u.ac.jp/en/top

Osaka University

Related Diabetes Articles from Brightsurf:

New diabetes medication reduced heart event risk in those with diabetes and kidney disease
Sotagliflozin - a type of medication known as an SGLT2 inhibitor primarily prescribed for Type 2 diabetes - reduces the risk of adverse cardiovascular events for patients with diabetes and kidney disease.

Diabetes drug boosts survival in patients with type 2 diabetes and COVID-19 pneumonia
Sitagliptin, a drug to lower blood sugar in type 2 diabetes, also improves survival in diabetic patients hospitalized with COVID-19, suggests a multicenter observational study in Italy.

Making sense of diabetes
Throughout her 38-year nursing career, Laurel Despins has progressed from a bedside nurse to a clinical nurse specialist and has worked in medical, surgical and cardiac intensive care units.

Helping teens with type 1 diabetes improve diabetes control with MyDiaText
Adolescence is a difficult period of development, made more complex for those with Type 1 diabetes mellitus (T1DM).

Diabetes-in-a-dish model uncovers new insights into the cause of type 2 diabetes
Researchers have developed a novel 'disease-in-a-dish' model to study the basic molecular factors that lead to the development of type 2 diabetes, uncovering the potential existence of major signaling defects both inside and outside of the classical insulin signaling cascade, and providing new perspectives on the mechanisms behind insulin resistance in type 2 diabetes and possibly opportunities for the development of novel therapeutics for the disease.

Tele-diabetes to manage new-onset diabetes during COVID-19 pandemic
Two new case studies highlight the use of tele-diabetes to manage new-onset type 1 diabetes in an adult and an infant during the COVID-19 pandemic.

Genetic profile may predict type 2 diabetes risk among women with gestational diabetes
Women who go on to develop type 2 diabetes after having gestational, or pregnancy-related, diabetes are more likely to have particular genetic profiles, suggests an analysis by researchers at the National Institutes of Health and other institutions.

Maternal gestational diabetes linked to diabetes in children
Children and youth of mothers who had gestational diabetes during pregnancy are at increased risk of diabetes themselves, according to new research published in CMAJ (Canadian Medical Association Journal).

Two diabetes medications don't slow progression of type 2 diabetes in youth
In youth with impaired glucose tolerance or recent-onset type 2 diabetes, neither initial treatment with long-acting insulin followed by the drug metformin, nor metformin alone preserved the body's ability to make insulin, according to results published online June 25 in Diabetes Care.

People with diabetes visit the dentist less frequently despite link between diabetes, oral health
Adults with diabetes are less likely to visit the dentist than people with prediabetes or without diabetes, finds a new study led by researchers at NYU Rory Meyers College of Nursing and East Carolina University's Brody School of Medicine.

Read More: Diabetes News and Diabetes Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.