JUN 01, 2016 12:27 PM PDT

Fighting Obesity with a Small Molecule to Stimulate Brown Adipose Tissue

WRITTEN BY: Cassidy Reich
More than two thirds of adults and about one third of children and adolescents are considered overweight or obese. The obesity epidemic has contributed to rising health costs by putting people at risk for many different diseases. Despite numerous efforts, obesity is still a huge problem.

Researchers have been searching for a way to utilize brown adipose tissue in the fight against obesity and metabolic disorders. Brown fat, or brown adipose tissue (BAT), is different from white adipose tissue (WAT) in a major way. Most people know that muscle is a thermogenic tissue and burns more energy at rest compared to fat. BAT, even though it is a type of fat, is also a thermogenic tissue and burns more energy compared to WAT. The idea is that increasing the amount of BAT would help to regulate energy homeostasis and fight obesity. The main issue with this strategy, which I’ve written about before,  is finding a way to safely stimulate BAT without causing harmful side effects.
 
Chemical structure of butein.

A recent paper published in Nature Chemical Biology describes the mechanism of action of a small molecule that they found that facilitates a process called “WAT browning.” In addition to WAT and BAT, there are certain fat cells referred to as beige adipocytes which are inducible brown-like adipocytes generated from WAT. These beige adipocytes have different origins than BAT, but can be induced to take on BAT-like characteristics, such as thermogenesis.

A gene called Ucp1 has been implicated in BAT function and in WAT browning. The researchers decided to screen for small molecules that would facilitate WAT browning using upregulated Ucp1 expression as the readout. From this screen, they found a small molecule called butein which is derived from the plant Rhus verniciflua Stokes. Butein had the most robust upregulation of Ucp1 mRNA expression and also induced expression of other brown adipocyte markers. In addition to upregulating BAT markers, butein suppressed expression of white-adipocyte-selective genes.

The researchers also wanted to figure out how butein upregulates Ucp1 and establishes the thermogenic program in adipocytes. To do this, they screened for changes in gene expression following butein exposure, focusing on transcription factors. From this screen, they identified the transcription factor gene Prdm4. Further testing of Prdm4’s involvement in obesity and butein’s mechanism of action showed that there is less Prdm4 expression in the WAT and BAT of obese mice and that Prdm4 expression is required for butein to induce WAT browning.

This exciting research describes a pathway that contributes to the induction of WAT browning and that can be regulated by small molecules. The ability to target this pathway with small molecules that don’t affect the adrenergic system is key because this could be a safer way to increase people’s basal metabolic rate. A small molecule that safely increases people’s energy output would be a potent weapon in the fight against obesity.  
About the Author
Cassidy is a curious person, and her curiosity has led her to pursue a PhD in Pharmacology at the New York University Sackler Institute of Biomedical Sciences. She likes to talk about science way too much, so now she's going to try writing about it.
You May Also Like
SEP 04, 2022
Drug Discovery & Development
Brief Exposure to Cancer Drug Produces Anti-aging Effects in Mice
SEP 04, 2022
Brief Exposure to Cancer Drug Produces Anti-aging Effects in Mice
Brief exposure to rapamycin, a promising anti-aging drug, may have similar effects on health and lifespan as longer trea ...
SEP 09, 2022
Immunology
Antibodies are Sometimes Made with 'Stolen' DNA
SEP 09, 2022
Antibodies are Sometimes Made with 'Stolen' DNA
The human immune system must respond to a diverse array of infectious agents and harmful invaders throughout our lifetim ...
SEP 15, 2022
Immunology
How a Cancer-Causing Virus Evades Human Immunity
SEP 15, 2022
How a Cancer-Causing Virus Evades Human Immunity
While our immune system is usually able to identify and destroy pathogenic invaders like bacteria and viruses, those mic ...
SEP 08, 2022
Drug Discovery & Development
Tired of Long COVID? A new drug shows promise to combat fatigue caused by long COVID
SEP 08, 2022
Tired of Long COVID? A new drug shows promise to combat fatigue caused by long COVID
If you are reading this, chances are you have had COVID; unless you are one of the few “super dodgers” ...
SEP 15, 2022
Cardiology
Lack of Sleep Increases Our Health Risks and Lowers Our Empathy
SEP 15, 2022
Lack of Sleep Increases Our Health Risks and Lowers Our Empathy
Lack of sleep is correlated with cardiovascular disease, depression, and more: it also makes us more selfish.
SEP 15, 2022
Health & Medicine
Take Micro-breaks to Improve Focus and Boost Wellness
SEP 15, 2022
Take Micro-breaks to Improve Focus and Boost Wellness
A brief break is better than no rest at all and possibly boosts productivity better than a longer break. Micro-breaks, d ...
Loading Comments...