Osaka: Scientists at Osaka University clarified that deletion of adipose
oxidative stress (Fat ROS) decreased lipid accumulation in the liver,
clinically improving insulin resistance and inducing metabolically
healthy obesity. In fact, Fat ROS suppressed lipid accumulation and
increased ectopic lipid accumulation in the liver, worsening insulin
resistance. Their research results were published in Diabetes on Wednesday, April 4, 2018.
In most people, obesity is caused by eating too much and moving too
little. There are two types of obesity: metabolically abnormal obesity
associated with insulin resistance and metabolic disorder and
metabolically healthy obesity without these complicating disorders;
however, the molecular mechanism behind this difference was unknown.
In 2004, a group of researchers led by Atsunori Fukuhara reported
that oxidative stress increased in the obese adipose tissues. However,
it was difficult to create a mouse model in which oxidative stress was
manipulated to target adipocytes. So, the causal role of Fat ROS in
obesity in vivo still remained unclear.
In their research, this group clarified the following: Fat
ROS-eliminated mice, in which two antioxidant enzymes (Catalase and
Sod1) were overexpressed in adipocytes using an adipocyte-specific aP2
promoter cassette, exhibited adipose expansion with decreased ectopic
lipid accumulation and improved insulin sensitivity. Conversely, Fat
ROS-augmented, Adipoq promoter-driven Cre transgenic mice, in which
antioxidant substance glutathione was depleted specifically in
adipocytes, exhibited restricted adipose expansion associated with
increased ectopic lipid accumulation and deteriorated insulin
sensitivity.
SREBF1 transcriptional activities were suppressed by oxidative
stress, suppressing expression of lipogenic genes in adipocytes, which
was found to be the underlying mechanism for suppression of de novo
lipogenesis by oxidative stress.
It is expected that the results of this study will lead to the
development of drugs targeting Fat ROS to induce healthy adipose
expansion, which will lead to treatment of obese type 2 diabetes.
Fig.1. Elimination of Fat ROS causes healthy obese.
(credit: Osaka University)
Fig.2. Fat ROS distinguish between healthy and pathological obese.
(credit: Osaka University)
To learn more about this research, please view the full research
report entitled "Oxidative stress inhibits healthy adipose expansion
through suppression of SREBF1-mediated lipogenic pathway" at this page of Diabetes.
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