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Obesity Linked To Self-Eating Beige Fat

by Federica Parisi PhD, September 13, 2016 at 04:41 PM | Tags

Humans, like all mammals, have two types of fat with completely opposite functions: white, which stores energy and when present in excess is linked with diabetes and obesity; and brown, which produces heat by burning energy and is associated with leanness. Recently, a third type of fat was discovered within white fat, called beige fat. Beige fat cells can quickly convert from an energy storing state to an energy burning state in response to environmental changes. UC San Francisco researchers studying beige fat have described a new strategy to preserve this beneficial tissue.

Human babies are born with brown fat, which they use as a natural defence against the cold. For a long time this metabolically active tissue was thought to be lost in adult life; however, the persistence of energy burning fat in adult life was recently demonstrated. Further studies helped us understand the real nature of this fat tissue, which is not classic brown fat but a new form of healthy adipose cells called “beige fat”.

Beige fat is found within white fat and has the ability to quickly convert from an energy storing “white” state to a calorie burning “brown” state in response to environmental changes, such as cold temperatures or other stressing conditions.

The discovery of beige fat was surrounded by much hype among obesity researchers who calculated that just two ounces of beige fat can burn up to 200 calories a day when the temperature drops, providing hope for application to obese patients.

However early clinical studies that looked into converting beige into brown fat by exposing patients to cold temperatures or by artificially tricking their body into thinking it’s cold have proven unsuccessful, because most obese people lack a significant amount of active beige fat. These approaches have also highlighted the risk of associated cardiovascular side effects in obese patients, which are incompatible with prolonged treatments.

A UC San Francisco research group headed by Dr Shingo Kajimura recently identified new pharmacological strategies for transforming white fat into beige fat in mice, without significant cardiovascular side effects. However, the treatment was only efficacious as long as mice were medicated. When treatments were stopped, the newly formed beige fat reverted back to white fat within weeks.

In a follow up study, the team set out to investigate the mechanisms underlying beige cell to white cell conversion and found that during this undesired transformation beige cells digest their own mitochondria, the subcellular units that are in charge of burning glucose to produce energy.

This could be prevented by deleting key genes that regulate autophagy, a physiological process that cells use to get rid of damaged organelles and prevent the accumulation of waste.

Further tests showed that blocking autophagy in fat cells helped mice retain beige fat longer and burn energy quicker, without any obvious differences in activity levels or appetite.

When these autophagy-depleted animals were placed on a high fat diet, they also gained considerably less weight and retained healthier glucose metabolism and insulin sensitivity, which are good indicators for Type 2 diabetes (T2D) patients.

These findings are encouraging and will hopefully lead to a better understanding of how we can help people keep more beige fat, and therefore stay healthier.

Understanding the mechanisms of the complex cluster of conditions called human metabolic syndrome, and how these lead to the development of obesity and T2D requires appropriate preclinical models to mimic the development of human disease.

CrownBio provides the most translatable animal models of human metabolic syndrome and T2D including the ZDSD Rat, a polygenic model that spontaneously becomes obese and diabetic on a normal diet. In the ZDSD Rat, T2D displays a similar progression to the human disease with a prediabetic state that is rarely found in other animal models. The ZDSD Rat develops all late stage T2D complications, including diabetic nephropathy, making this model extremely valuable for the evaluation of antidiabetic agents that target various aspects of the disease.

To learn more about the ZDSD Rat and our newly developed translational platform for human metabolic syndrome and T2D contact us today.


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